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2<HTML>
3<HEAD>
4<TITLE>main</TITLE>
5<META NAME="description" CONTENT="main">
6<META NAME="keywords" CONTENT="PHYLIP", "main", "documentation">
7<META NAME="resource-type" CONTENT="document">
8<META NAME="distribution" CONTENT="global">
9<META HTTP-EQUIV="Content-Type" CONTENT="text/html; charset=iso-8859-1">
10</HEAD>
11<BODY BGCOLOR="#ccffff">
12<P>
13<DIV ALIGN="CENTER">
14<H1>PHYLIP</H1>
15<H2>Phylogeny Inference Package</H2>
16<P>
17<IMG SRC="phylip.gif" ALT="PHYLIP Logo">
18<P>
19<H3>Version 3.6(alpha3)</H3>
20<P>
21<H3>July, 2002</H3>
22<P>
23<H2>by Joseph Felsenstein</H2>
24<P>
25<BR>
26<TABLE>
27<TR><TD>
28<FONT SIZE="+2">
29Department of Genome Sciences<BR>
30University of Washington<BR>
31Box 357730<BR>
32Seattle, WA &nbsp;&nbsp;98195-7730<BR>
33USA
34</FONT>
35</TD></TR>
36</TABLE>
37<H2>E-mail address: <TT>joe@gs.washington.edu</TT></H2>
38</DIV>
39<P>
40<DIV ALIGN="CENTER">
41<A NAME="contents"><HR><P></A>
42<H2>Contents of this document</H2></DIV>
43<P>
44<BR>
45<A HREF="#contents">Contents of this document
46<BR>
47<A HREF="#description">A Brief Description of the Programs</A>
48<BR>
49<A HREF="#copyright">Copyright Notice for PHYLIP</A>
50<BR>
51<A HREF="#documentation">The Documentation Files and How to Read Them</A>
52<BR>
53<A HREF="#programs">What The Programs Do</A>
54<BR>
55<A HREF="#running">Running the Programs</A>
56<BR>
57&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;A word about input files
58<BR>
59&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Running the programs on a Windows machine
60<BR>
61&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Running the programs on a Macintosh
62<BR>
63&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Running the programs on a Unix system
64<BR>
65&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Running the programs in MSDOS
66<BR>
67&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Running the programs in background or under control of a command file
68<BR>
69<A HREF="#inputfiles">Preparing Input Files</A>
70<BR>
71&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Input and output files
72<BR>
73&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Data file format
74<BR>
75<A HREF="#menu">The Menu</A>
76<BR>
77<A HREF="#outputfile">The Output File</A>
78<BR>
79<A HREF="#treefile">The Tree File</A>
80<BR>
81<A HREF="#options">The Options and How To Invoke Them</A>
82<BR>
83&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Common options in the menu
84<BR>
85&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;The <TT>U</TT> (User tree) option
86<BR>
87&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;The <TT>G</TT> (Global) option
88<BR>
89&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;The <TT>J</TT> (Jumble) option
90<BR>
91&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;The <TT>O</TT> (Outgroup) option
92<BR>
93&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;The <TT>T</TT> (Threshold) option
94<BR>
95&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;The <TT>M</TT> (Multiple data sets) option
96<BR>
97&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;The <TT>W</TT> (Weights) option
98<BR>
99&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;The option to write out the trees into a tree file
100<BR>
101&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;The (<TT>0</TT>) terminal type option
102<BR>
103<A HREF="#algorithm">The Algorithm for Constructing Trees</A>
104<BR>
105&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Local Rearrangements
106<BR>
107&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Global Rearrangements
108<BR>
109&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Multiple Jumbles
110<BR>
111&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Saving multiple tied trees
112<BR>
113&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Strategy for Finding the Best Tree
114<BR>
115<A HREF="#warning">A Warning on Interpreting Results</A>
116<BR>
117<A HREF="#speed">Relative Speed of Different Programs and Machines</A>
118<BR>
119&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Relative speed of the different programs
120<BR>
121&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Speed with different numbers of species
122<BR>
123&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Relative speed of different machines
124<BR>
125<A HREF="#comments">General Comments on Adapting the Package to Different Computer Systems</A>
126<BR>
127<A HREF="#compiling">Compiling the programs</A>
128<BR>
129&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Unix and Linux
130<BR>
131&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Macintosh PowerMacs
132<BR>
133&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Compiling with Metrowerks Codewarrior
134<BR>
135&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;On Windows systems
136<BR>
137&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Compiling with Microsoft Visual C++
138<BR>
139&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Compiling with Borland C++
140<BR>
141&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Compiling with Metrowerks Codewarrior for Windows
142<BR>
143&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Compiling with Cygnus Gnu C++
144<BR>
145&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;VMS VAX systems
146<BR>
147&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Parallel computers
148<BR>
149&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Other computer systems
150<BR>
151<A HREF="#FAQ">Frequently Asked Questions</A>
152<BR>
153&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;How to make it do various things
154<BR>
155&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Background information needed:
156<BR>
157&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Questions about distribution and citation:
158<BR>
159&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Questions about documentation
160<BR>
161&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Additional Frequently Asked Questions, or: "Why didn't it occur to you to ...
162<BR>
163&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;(Fortunately) obsolete questions
164<BR>
165<A HREF="#newfeatures">New Features in This Version</A>
166<BR>
167<A HREF="#future">Coming Attractions, Future Plans</A>
168<BR>
169<A HREF="#endorsements">Endorsements</A>
170<BR>
171&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;From the pages of <I>Cladistics</I>
172<BR>
173&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;... and in the pages of other journals:
174<BR>
175<A HREF="#references">References for the Documentation Files</A>
176<BR>
177<A HREF="#credits">Credits</A>
178<BR>
179<A HREF="#otherprograms">Other Phylogeny Programs Available Elsewhere</A>
180<BR>
181&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;PAUP*
182<BR>
183&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;MacClade
184<BR>
185&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;MEGA
186<BR>
187&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;MOLPHY
188<BR>
189&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;PAML
190<BR>
191&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;TREE-PUZZLE
192<BR>
193&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;DAMBE
194<BR>
195&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Hennig86
196<BR>
197&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;RnA
198<BR>
199&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;NONA
200<BR>
201&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;TNT
202<BR>
203<A HREF="#helpme">How You Can Help Me</A>
204<BR>
205<A HREF="#trouble">In Case of Trouble</A>
206<P>
207<A NAME="description"><HR><P></A>
208<DIV ALIGN="CENTER">
209<H2>A Brief Description of the Programs</H2></DIV>
210<P>
211<TT>PHYLIP</TT>, the Phylogeny Inference Package, is a package of programs for
212inferring phylogenies (evolutionary trees).  It has been distributed since
2131980, and has over 10,000 registered users, making it the most widely
214distributed package of phylogeny programs.  It is available free, from
215its web site:
216<P>
217<DIV ALIGN="CENTER">
218<FONT SIZE=+2><A HREF="http://evolution.gs.washington.edu/phylip.html">
219<TT>http://evolution.gs.washington.edu/phylip.html</TT></A></FONT>
220
221</DIV>
222<P>
223<TT>PHYLIP</TT> is available as source code in C, and also as executables for
224some common computer systems.  It can infer phylogenies by parsimony,
225compatibility, distance matrix methods, and likelihood.  It can also
226compute consensus trees, compute distances between trees, draw trees,
227resample data sets by bootstrapping or jackknifing, edit trees, and
228compute distance matrices.  It can handle data that are nucleotide
229sequences, protein sequences, gene frequencies, restriction sites,
230restriction fragments, distances, discrete characters, and continuous
231characters.
232<P>
233<BR>
234<A NAME="copyright"><HR><P></A>
235<DIV ALIGN=CENTER>
236<TABLE BORDER=4 WIDTH=80%><TR><TD ALIGN=LEFT>
237<DIV ALIGN="CENTER">
238<H2>Copyright Notice for PHYLIP</H2></DIV>
239<P>
240The following copyright notice is intended to cover all source code, all
241documentation, and all executable programs of the PHYLIP package.
242<P>
243&#169; Copyright 1980-2002.  University of Washington and Joseph Felsenstein.  All
244rights reserved.  Permission is granted to reproduce, perform, and modify
245these programs and documentation files.  Permission is granted to distribute
246or provide access to these
247programs provided that this copyright notice is not removed, the programs are
248not integrated with or called by any product or service that generates
249revenue, and that your distribution of these materials program are free.
250Any modified
251versions of these materials that are distributed or accessible shall indicate
252that they are based on these program.  Institutions of higher education are
253granted permission to distribute this material to their students and staff
254for a fee to recover distribution costs.  Permission requests for any other
255distribution of this program should be directed to <TT>license@u.washington.edu</TT>.
256<BR>
257</TD></TR></TABLE></DIV>
258
259<BR>
260<A NAME="documentation"><HR><P></A>
261<DIV ALIGN="CENTER">
262<H2>The Documentation Files and How to Read Them</H2></DIV>
263<P>
264<TT>PHYLIP</TT> comes with an extensive set of documentation files.  These
265include the main documentation file (this one), which you should read
266fairly completely.  In addition there are files for groups of programs,
267including ones for the <A HREF="sequence.html">molecular sequence</A>
268programs, the <A HREF="distance.html">distance matrix</A>
269programs, the
270<A HREF="contchar.html">gene frequency and continuous characters</A>
271programs, the <A HREF="discrete.html">discrete characters</A> programs,
272and the <A HREF="draw.html">tree drawing</A> programs.  Finally,
273each program has its own documentation file.  References for the
274documentation files are all gathered together in this main documentation
275file.  A good strategy is to:
276<OL>
277<LI>Read this main documentation file.
278<LI>Tentatively decide which programs are of interest to you.
279<LI>Read the documentation files for the groups of programs that
280contain those.
281<LI>Read the documentation files for those individual programs.
282</OL>
283<P>
284<A NAME="programs"><HR><P></A>
285<DIV ALIGN="CENTER">
286<H2>What The Programs Do</H2></DIV>
287<P>
288Here is a short description of each of the programs.  For more detailed
289discussion you should definitely read the documentation file for the
290individual program and the documentation file for the group of programs
291it is in.  In this list the name of each program is a link which will
292take you to the documentation file for that program.  Note that there is no
293program in the PHYLIP package called PHYLIP.
294<DL>
295<DT><STRONG><A HREF="protpars.html">PROTPARS</A></STRONG>
296<DD>Estimates phylogenies from protein sequences (input using the
297   standard one-letter code for amino acids) using the parsimony method, in
298   a variant which counts only those nucleotide changes that change the amino
299   acid, on the assumption that silent changes are more easily accomplished.
300<DT><STRONG><A HREF="dnapars.html">DNAPARS</A></STRONG>
301<DD>Estimates phylogenies by the parsimony method using nucleic acid
302   sequences.  Allows use the full IUB ambiguity codes, and estimates
303   ancestral nucleotide states.  Gaps treated as a fifth nucleotide state.
304   Can use 0/1 weights, reconstruct ancestral states, and infer branch
305   lengths.
306<DT><STRONG><A HREF="dnamove.html">DNAMOVE</A></STRONG>
307<DD>Interactive construction of phylogenies from nucleic acid
308   sequences, with their evaluation by parsimony and compatibility and the
309   display of reconstructed ancestral bases.  This can be used to find
310   parsimony or compatibility estimates by hand. 
311<DT><STRONG><A HREF="dnapenny.html">DNAPENNY</A></STRONG>
312<DD>Finds all most parsimonious phylogenies for nucleic acid
313   sequences by branch-and-bound search.  This may not be practical (depending
314   on the data) for more than 15 species or so.
315<DT><STRONG><A HREF="dnacomp.html">DNACOMP</A></STRONG>
316<DD>Estimates phylogenies from nucleic acid sequence data using
317   the compatibility criterion, which searches for the largest number of sites
318   which could have all states (nucleotides) uniquely evolved on the same
319   tree.  Compatibility is particularly appropriate when sites vary greatly in
320   their rates of evolution, but we do not know in advance which are the less
321   reliable ones.
322<DT><STRONG><A HREF="dnainvar.html">DNAINVAR</A></STRONG>
323<DD>For nucleic acid sequence data on four species, computes
324   Lake's and Cavender's phylogenetic invariants, which test alternative tree
325   topologies.  The program also tabulates the frequencies of occurrence of the
326   different nucleotide patterns.  Lake's invariants are the method which he
327   calls "evolutionary parsimony".
328<DT><STRONG><A HREF="dnaml.html">DNAML</A></STRONG>
329<DD>Estimates phylogenies from nucleotide sequences by maximum
330   likelihood.  The model employed allows for unequal expected frequencies of
331   the four nucleotides, for unequal rates of transitions and transversions,
332   and for different (prespecified) rates of change in different categories of
333   sites, with the program inferring which sites have which rates.  It also
334   allows different rates of change at known sites.
335<DT><STRONG><A HREF="dnamlk.html">DNAMLK</A></STRONG>
336<DD>Same as DNAML but assumes a molecular clock.  The use of the
337   two programs together permits a likelihood ratio test of the
338   molecular clock hypothesis to be made.
339<DT><STRONG><A HREF="proml.html">PROML</A></STRONG>
340<DD>Estimates phylogenies from protein amino acid sequences by maximum
341   likelihood.  The PAM or JTTF models can be employed.  The program
342   can allow for different (prespecified) rates of change in different
343   categories of amino acid positions, with the program inferring which
344   posiitons have which rates.  It also allows different rates of change
345   at known sites.
346<DT><STRONG><A HREF="promlk.html">PROMLK</A></STRONG>
347<DD>Same as PROML but assumes a molecular clock.  The use of the
348   two programs together permits a likelihood ratio test of the
349   molecular clock hypothesis to be made.
350<DT><STRONG><A HREF="dnadist.html">DNADIST</A></STRONG>
351<DD>Computes four different distances between species from nucleic
352   acid sequences.  The distances can then be used in the distance matrix
353   programs.  The distances are the Jukes-Cantor formula, one based on Kimura's
354   2-parameter method, Jin and Nei's distance which allows for rate variation
355   from site to site, and a maximum likelihood method using the model employed
356   in DNAML.  The latter method of computing distances can be very slow.
357<DT><STRONG><A HREF="protdist.html">PROTDIST</A></STRONG>
358<DD>Computes a distance measure for protein sequences, using
359   maximum likelihood estimates based on the Dayhoff PAM matrix, Kimura's 1983
360   approximation to it, or a model based on the genetic code plus a
361   constraint on changing to a different category of amino acid.  Rate
362   variation from site to site is also allowed.  The
363   distances can be used in the distance matrix programs.
364<DT><STRONG><A HREF="restdist.html">RESTDIST</A></STRONG>
365<DD>Distances calculated from restriction sites data or
366   restriction fragments data.  The restriction sites option is the one to
367   use to also make distances for RAPDs or AFLPs.
368<DT><STRONG><A HREF="restml.html">RESTML</A></STRONG>
369<DD>Estimation of phylogenies by maximum likelihood using
370   restriction sites data (not restriction fragments but presence/absence of
371   individual sites).  It employs the Jukes-Cantor symmetrical model of
372   nucleotide change, which does not allow for differences of rate between
373   transitions and transversions.  This program is <I>very</I> slow.
374<DT><STRONG><A HREF="seqboot.html">SEQBOOT</A></STRONG>
375<DD>Reads in a data set, and produces multiple data sets from
376   it by bootstrap resampling.  Since most programs in the current version of
377   the package allow processing of multiple data sets, this can be used
378   together with the consensus tree program CONSENSE to do bootstrap (or
379   delete-half-jackknife) analyses with most of the methods in this package.
380   This program also allows the Archie/Faith technique of permutation of
381   species within characters.  It can also rewrite a data set to convert
382   it from between the PHYLIP Interleaved and Sequential forms, and into
383   a preliminary version of a new XML sequence alignment format
384   which is under development.
385<DT><STRONG><A HREF="fitch.html">FITCH</A></STRONG>
386<DD>Estimates phylogenies from distance matrix data under the
387   "additive tree model" according to which the distances are expected to
388   equal the sums of branch lengths between the species.  Uses the
389   Fitch-Margoliash criterion and some related least squares criteria.  Does
390   not assume an evolutionary clock.  This program will be useful with
391   distances computed from molecular sequences, restriction sites or fragments
392   distances, with DNA hybridization measurements, and with genetic distances
393   computed from gene frequencies.
394<DT><STRONG><A HREF="kitsch.html">KITSCH</A></STRONG>
395<DD>Estimates phylogenies from distance matrix data under the
396   "ultrametric" model which is the same as the additive tree model except
397   that an evolutionary clock is assumed.  The Fitch-Margoliash criterion and
398   other least squares criteria are assumed.  This program will be useful with
399   distances computed from molecular sequences, restriction sites or
400   fragments distances, with distances from DNA hybridization measurements,
401   and with genetic distances computed from gene frequencies.
402<DT><STRONG><A HREF="neighbor.html">NEIGHBOR</A></STRONG>
403<DD>An implementation by Mary Kuhner and John Yamato of Saitou and
404   Nei's "Neighbor Joining Method," and of the UPGMA (Average Linkage
405   clustering) method.  Neighbor Joining is a distance matrix method producing
406   an unrooted tree without the assumption of a clock.  UPGMA does assume a
407   clock.  The branch lengths are not optimized by the least squares criterion
408   but the methods are very fast and thus can handle much larger data sets.
409<DT><STRONG><A HREF="contml.html">CONTML</A></STRONG>
410<DD>Estimates phylogenies from gene frequency data by maximum
411   likelihood under a model in which all divergence is due to genetic drift in
412   the absence of new mutations.  Does not assume a molecular clock.  An
413   alternative method of analyzing this data is to compute Nei's genetic
414   distance and use one of the distance matrix programs.
415   This program can also do maximum likelihoodn analysis of continuous
416   charactersn that evolve by a Brownian Motion model, but it assumes that
417   the characters evolve at equal rates and in an uncorrelated fashion, so
418   that it does not take into account the usual correlations of characters.
419<DT><STRONG><A HREF="gendist.html">GENDIST</A></STRONG>
420<DD>Computes one of three different genetic distance formulas
421   from gene frequency data.  The formulas are Nei's genetic distance, the
422   Cavalli-Sforza chord measure, and the genetic distance of Reynolds et. al.
423   The former is appropriate for data in which new mutations occur in an
424   infinite isoalleles neutral mutation model, the latter two for a model
425   without mutation and with pure genetic drift.  The distances are written to
426   a file in a format appropriate for input to the distance matrix programs.
427<DT><STRONG><A HREF="contrast.html">CONTRAST</A></STRONG>
428<DD>Reads a tree from a tree file, and a data set with continuous
429   characters data, and produces the independent contrasts for those
430   characters, for use in any multivariate statistics package.  Will also
431   produce covariances, regressions and correlations between characters for
432   those contrasts.  Can also correct for within-species sampling variation
433   when individual phenotypes are available within a population.
434<DT><STRONG><A HREF="pars.html">PARS</A></STRONG>
435<DD>Multistate discrete-characters parsimony method.   Up to 8 states
436  (as well as "<TT>?</TT>") are allowed.  Cannot do Camin-Sokal or Dollo Parsimony.
437  Can reconstruct ancestral states, use character weights, and infer branch
438  lengths.
439<DT><STRONG><A HREF="mix.html">MIX</A></STRONG>
440<DD>Estimates phylogenies by some parsimony methods for discrete
441   character data with two states (0 and 1).  Allows use of the
442   Wagner parsimony method, the Camin-Sokal parsimony method, or arbitrary
443   mixtures of these.  Also reconstructs ancestral states and allows weighting
444   of characters (does not infer branch lengths).
445<DT><STRONG><A HREF="move.html">MOVE</A></STRONG>
446<DD>Interactive construction of phylogenies from discrete character
447   data with two states (0 and 1).  Evaluates parsimony and compatibility
448   criteria for those phylogenies and displays reconstructed states throughout
449   the tree.  This can be used to find parsimony or compatibility estimates by
450   hand.
451<DT><STRONG><A HREF="penny.html">PENNY</A></STRONG>
452<DD>Finds all most parsimonious phylogenies for discrete-character
453   data with two states, for the Wagner, Camin-Sokal, and mixed parsimony
454   criteria using the branch-and-bound method of exact search.  May be
455   impractical (depending on the data) for more than 10-11 species.
456<DT><STRONG><A HREF="dollop.html">DOLLOP</A></STRONG>
457<DD>Estimates phylogenies by the Dollo or polymorphism parsimony
458   criteria for discrete character data with two states (0 and 1).  Also
459   reconstructs ancestral states and allows weighting of characters.  Dollo
460   parsimony is particularly appropriate for restriction sites data; with
461   ancestor states specified as unknown it may be appropriate for restriction
462   fragments data.
463<DT><STRONG><A HREF="dolmove.html">DOLMOVE</A></STRONG>
464<DD>Interactive construction of phylogenies from discrete
465   character data with two states (0 and 1) using the Dollo or polymorphism
466   parsimony criteria.  Evaluates parsimony and compatibility criteria for
467   those phylogenies and displays reconstructed states throughout the tree.
468   This can be used to find parsimony or compatibility estimates by hand.
469<DT><STRONG><A HREF="dolpenny.html">DOLPENNY</A></STRONG>
470<DD>Finds all most parsimonious phylogenies for
471    discrete-character data with two states, for the Dollo or polymorphism
472   parsimony criteria using the branch-and-bound method of exact search.  May
473   be impractical (depending on the data) for more than 10-11 species.
474<DT><STRONG><A HREF="clique.html">CLIQUE</A></STRONG>
475<DD>Finds the largest clique of mutually compatible characters, and
476   the phylogeny which they recommend, for discrete character data with two
477   states.  The largest clique (or all cliques within a given size range of
478   the largest one) are found by a very fast branch and bound search method. 
479   The method does not allow for missing data.  For such cases the <TT>T</TT>
480   (Threshold) option of PARS or MIX may be a useful alternative.
481   Compatibility methods are particular useful when some characters are of
482   poor quality and the rest of good quality, but when it is not known in
483   advance which ones are which.
484<DT><STRONG><A HREF="factor.html">FACTOR</A></STRONG>
485<DD>Takes discrete multistate data with character state trees and
486   produces the corresponding data set with two states (0 and 1).  Written by
487   Christopher Meacham.  This program was formerly used to accomodate
488   multistate characters in MIX, but this is less necessary now that PARS is
489   available.
490<DT><STRONG><A HREF="drawgram.html">DRAWGRAM</A></STRONG>
491<DD>Plots rooted phylogenies, cladograms, and phenograms in a
492   wide variety of user-controllable formats.  The program is interactive and
493   allows previewing of the tree on PC or Macintosh graphics screens,
494   and Tektronix or Digital graphics terminals.  Final output can be
495   to a file formatted for one of the drawing programs, on
496   a laser printer (such as Postscript or PCL-compatible printers),
497   on graphics screens or terminals, on pen plotters (Hewlett-Packard or
498   Houston Instruments) or on dot matrix printers capable of graphics
499   (Epson, Okidata, Imagewriter, or Toshiba).
500<DT><STRONG><A HREF="drawtree.html">DRAWTREE</A></STRONG>
501<DD>Similar to DRAWGRAM but plots unrooted phylogenies.
502<DT><STRONG><A HREF="treedist.html">TREEDIST</A></STRONG>
503<DD>Computes the Robinson-Foulds symmetric difference distance
504   between trees, which allows for differences in tree topology (but does not
505   use branch lengths).
506<DT><STRONG><A HREF="consense.html">CONSENSE</A></STRONG>
507<DD>Computes consensus trees by the majority-rule consensus tree
508   method, which also allows one to easily find the strict consensus tree. 
509   Is not able to compute the Adams consensus tree.  Trees are input in a tree
510   file in standard nested-parenthesis notation, which is produced by many of
511   the tree estimation programs in the package.  This program can be used as
512   the final step in doing bootstrap analyses for many of the methods in the
513   package.
514<DT><STRONG><A HREF="retree.html">RETREE</A></STRONG>
515<DD>Reads in a tree (with branch lengths if necessary) and allows
516   you to reroot the tree, to flip branches, to change species names and
517   branch lengths, and then write the result out.  Can be used to convert
518   between rooted and unrooted trees, and to write the tree into a
519   preliminary version of a new XML tree file format which is under
520   development.
521</DL>
522<P>
523<A NAME="running"><HR><P></A>
524<DIV ALIGN="CENTER">
525<H2>Running the Programs</H2></DIV>
526<P>
527This section assumes that you have obtained PHYLIP as compiled executables
528(for Windows, Macintosh, or DOS), or have obtained the source code
529and compiled it yourself (for Linux, Unix, or OpenVMS).   For machines for
530which compiled executables are available, there will usually be no need for
531you to have a compiler or compile the programs yourself.  This section
532describes how to run the programs.  Later in this document we will
533discuss how to download and install PHYLIP (in case you are somehow
534reading this without yet having done that).  Normally you will only read
535this document after downloading and installing PHYLIP.
536<P>
537<H3>A word about input files.</H3>
538<P>
539For all of these types of machines, it is
540important to have the input files for the programs (typically data files)
541prepared in advance.  They can be prepared in any editor, but it is important
542that they be saved in Text Only ("flat ASCII") format, not in the format that
543word processors such as Microsoft Word want to write.  It is up to you to read
544the PHYLIP documentation files which describe the files formats that are
545needed.  There is a partial description in the next section of this document.
546The input files can also be obtained by running a program that
547produces output files in PHYLIP format (some of these programs do, and so do
548programs by others such as sequence alignment programs such as ClustalW and
549sequence format conversion programs such as Readseq).   There is <I>not</I> any
550input file editor available in any program in PHYLIP (you should <I>not</I>
551simply start running one of the programs and then expect to click a mouse
552somewhere to start creating a data file). 
553<P>
554When they start running, the programs look first for input files with
555particular names (such as <TT>infile</TT>, <TT>treefile</TT>,  <TT>intree</TT>, or <TT>fontfile</TT>).
556Exactly which file names they look for varies a bit from program to program,
557and you should read the documentation file for the particular program to
558find out.  If you have files with those names the programs will use them
559and not ask you for the file name.  If they do not find files of those
560names, the programs will say that they cannot find a file of that name, and
561ask you to type in the file name.
562For example, if DnaML looks
563for the file <TT>infile</TT> and does not find one of that name,
564it prints the message:
565<P>
566<TABLE><TR><TD BGCOLOR=white>
567<TT>dnaml: can't find input file "infile"<BR>
568Please enter a new file name></TT>
569</TD></TR></TABLE>
570<P><I>This does not mean that an error
571has occurred.</I>  All you need to do is to type in the name of the file.
572<P>
573The program looks for the input files in the same directory that the
574program is in (a directory is the same thing as a "folder").  In Windows, Linux, Unix, or MSDOS, if you are asked for the
575file name you can type in the path to the file, as part of the name (thus,
576if the file is in the directory above the current one, you can type in
577a file name such as <TT>../myfile.dna</TT>).   If you do not know what a
578"directory" is, or what "above" means, then you are a member of the new
579generation who just clicks the mouse and assumes that a list of file names
580will magically appear.  (Typically members of this generation have no idea
581where the files are on their system, and accumulate enormous amounts of
582unnecessary clutter in their file systems.)  In this case you should ask
583someone to explain directories to you.
584<P>
585<H3>Running the programs on a Windows machine.</H3>
586<P>
587Double-click on the icon for
588the program.  A window should open with a menu in it.  Further dialog with the
589program occurs
590by typing on the keyboard in response to what you see in the window.  The
591programs can be interrupted either by typing Control-C (which means to
592press down on the <TT>Ctrl</TT> key while typing the letter <TT>C</TT>), or by using
593the mouse to open the <TT>File</TT> menu in the upper-left corner of the program's
594window area and then select <TT>Quit</TT>.  Other than this, most PHYLIP programs
595make no use of the mouse.  The tree-drawing programs Drawtree and Drawgram
596do allow use of the mouse to select some options.
597<P>
598<H3>Running the programs on a Macintosh.</H3>
599<P>
600Double-click on the icon for
601the program.  A window should open.  Further dialog with the program occurs
602by typing on the keyboard in response to what you see in the window.  The
603programs can be interrupted by using
604the mouse to open the <TT>File</TT> menu in the upper-left corner of the program's
605window area and then select <TT>Quit</TT>.  Alternatively, you can use the
606Command-Q key combination.
607<P>
608When you use Quit, the program will ask you whether you want to save
609a file whose name is the program name (often followed by <TT>.out</TT> -- for
610example, if you are using DNAML it will ask you if you want to save file
611<TT>Dnaml.out</TT>.  This file is simply a record of everything that
612displayed on the program window, and you usually will not want to save it.
613Pressing the <TT>Enter</TT> key or selecting the Do Not Save button with
614the mouse will keep this from being saved.
615<P>
616If you encounter memory limitations on a Macintosh, and determine that
617this is not due to a problem with the format of the input file, as it
618often will be, you may be able to solve it by raising the limits of the
619stack and heap sizes of the program.  To do this click on the program
620and then select <TT>Get Info</TT> from the Finder <TT>File</TT> menu.
621This will open a window which can be made to show the memory limits
622of the program.  These can be changed by selecting them and typing in
623larger numbers.  This may relieve nagging memory problems.  If it does
624not, consult your local documentation and suspect problems with your
625input file format.
626<P>
627<H3>Running the programs on a Unix system.</H3>
628<P>
629Type the name of the program
630in lower-case letters (such as <TT>dnaml</TT>).  To interrupt the program while
631it is running, type Control-C (which means to press down on the <TT>Ctrl</TT> key
632while typing the letter <TT>C</TT>).
633<P>
634<H3>Running the programs in MSDOS.</H3>
635<P>
636Type the name of the program
637in lower-case letters (such as <TT>dnaml</TT>).  To interrupt the program while
638it is running, type Control-C (which means to press down on the <TT>Ctrl</TT> key
639while typing the letter <TT>C</TT>). 
640<P>
641<H3>Running the programs in background or under control of a command file</H3>
642<P>
643In running the programs, you may sometimes want to put them in background
644so you can proceed with other work.  On systems with a windowing environment
645they can be put in their own window, and commands like the Unix and Linux
646<TT>nice</TT> command used to make
647them have lower priority so that they do not interfere with interactive
648applications in other windows.  This part of the discussion will
649assume either a Windows system or a Unix or Linux system.  I will
650note when the commands work on one of these systems but not the other.
651Running jobs in background on Macintosh systems is an arcane art into whose
652mysteries I have not been initiated (or perhaps no one has been initiated).
653<P>
654If there is no windowing
655environment, on a Unix or Linux system you will want to use an
656ampersand (<TT>&amp;</TT>) after the command file name when invoking it to put the
657job in the background.  You will have to put all the responses to the
658interactive menu of the program into a file and tell the background job
659to take its input from that file.
660On Windows systems there is no <TT>&amp;</TT> or <TT>nice</TT> command
661but input and output redirection and command files work fine, with the sole
662difference that the a file of commands must have a name ending in
663<TT>.BAT</TT>, such as <TT>FOOFILE.BAT</TT>.
664<P>
665For example: suppose you want to run DNAPARS in a background, taking its
666input data from a file called <TT>sequences.dat</TT>, putting its interactive
667output to file called <TT>screenout</TT>, and using a file called <TT>input</TT> as
668the place to store the interactive input.  The file <TT>input</TT> need only
669contain two lines:
670<P>
671<TABLE><TR><TD bgcolor=white>
672<PRE>
673sequences.dat
674Y
675</PRE>
676</TD></TR></TABLE>
677<P>
678which is what you would have typed to run the program interactively, in
679response to the program's request for an input file name if it did not
680find a file named <TT>infile</TT>, in in response the the menu.
681<P>
682To run the program in background, in Unix or Linux you would simply give the command:
683<P>
684<TT>dnapars &lt; input &gt; screenout &amp;
685</TT>
686<P>
687These run the program with input responses coming from <TT>input</TT> and
688interactive output being put into file <TT>screenout</TT>.  The usual output
689file and tree file will also be created by this run (keep that in mind
690as if you run any other PHYLIP program from the same directory while
691this one is running in background you may overwrite the output file from
692one program with that from the other!).
693<P>
694If you wanted to give the program lower priority, so that it would
695not interfere with other work, and you have Berkeley Unix type job control
696facilities in your Unix or Linux (and you usually do), you can use the
697<TT>nice</TT> command:
698<P>
699<TT>nice +10 dnapars &lt; input &gt; screenout &amp;
700</TT>
701<P>
702which lowers the priority of the run.  To also time the run and put the
703timing at the end of <TT>screenout</TT>, you can do this:
704<P>
705<TT>nice +10 ( time dnapars &lt; input ) &gt;&amp; screenout &amp;
706</TT>
707<P>
708which I will not attempt to explain.
709<P>
710On Unix or Linux systems
711you may also want to explore putting the interactive output into the
712null file <TT>/dev/null</TT> so as to not be bothered with it (but then you
713cannot look at it to see why something went wrong).  If you have problems
714with creating output files that are too large, you may want to
715explore carefully the turning off of options in the programs you run.
716<P>
717If you are doing several runs in one, as for example when you do a
718bootstrap analysis using SEQBOOT, DNAPARS (say), and CONSENSE, you
719can use an editor to create a "command file" with these commands:
720<P>
721<TABLE><TR><TD bgcolor=white>
722<PRE>
723seqboot < input1 > screenout
724mv outfile infile
725dnapars < input2 >> screenout
726mv outtree intree
727consense < input3 >> screenout
728</PRE>
729</TD></TR></TABLE>
730<P>
731This is the Unix or Linux version -- in the MSDOS version, the renaming
732of files and the appending of output to the file <TT>screenout</TT> is
733handled differently.
734<P>
735On Unix or Linux the command file might be named something like
736<TT>foofile</TT>, and on Windows systems might be named <TT>foofile.bat</TT>.
737<P>
738On Unix or Linux the command file must be given
739execute permission by using the command  <TT>chmod +x foofile</TT> followed
740by the command <TT>rehash</TT>.  The job that <TT>foofile</TT> describes
741can be run in background on Unix or Linux by giving the command
742<P>
743<TT>foofile &amp;</TT>
744<P>
745On Windows systems it can be run by
746clicking on the icon of the command file.  Its icon will have a little gear
747symbol.
748<P>
749Note that you must also have the interactive input
750commands for SEQBOOT (including the random number seed), DNAPARS, and
751CONSENSE in the separate files <TT>input1</TT>, <TT>input2</TT>, and <TT>input3</TT>.
752Note that when PHYLIP programs attempt to open a new output file (such as
753<TT>outfile</TT>, <TT>outtree</TT>, or <TT>plotfile</TT>, if they see
754a file of that name already in existence they will ask you if you want to
755overwrite it, and offer alternatives including writing to another file,
756appending information to that file, or quitting the program without writing to
757the file.  This means that in writing batch files it is important to know
758whether there will be a prompt of this sort.  You must know in advance
759whether the file will exist.  You may want to put in your batch file a
760command that tests for the existence of a pre-existing output file and
761if so, removes it.  You might even want to put in a command that creates a
762file of that name, so that you can be sure it is there!  Either way,
763you will then know whether to put into your file of keyboard responses the
764proper response to the inquiry about overwriting that output file.
765<P>
766<A NAME="inputfiles"><HR><P></A>
767<DIV ALIGN="CENTER">
768<H2>Preparing Input Files</H2></DIV>
769<P>
770The input files for PHYLIP programs must be prepared separately - there is
771no data editor within PHYLIP.  You can use a word processor (or text
772editor) to prepare them yourself, or you can use a program that produces
773a PHYLIP-format output.  Sequence alignment programs such as ClustalW
774commonly have an option to produce PHYLIP files as output, and some
775other phylogeny programs, such as MacClade and TreeView, are capable of
776producing a PHYLIP-format file.
777<P>
778The format of the input files is discussed below, and you should also
779read the other PHYLIP documentation relevant to the particular type of
780data that you are using, and the particular programs you want to run, as
781there will be more details there.
782<P>
783It is very important that the input files be in "Text Only" or "flat
784ASCII" format.  This means that they contain only printable ASCII/ISO
785characters, and not any unprintable characters.  Many word processors such
786as Microsoft Word save their files in a format that contains unprintable
787characters, unless you tell them not to.  For Microsoft Word you can
788select <TT>Save As</TT> from its <TT>File</TT> menu, and choose <TT>Text Only</TT>
789as the file format.  This can also be done in WordPad utility in Windows .
790Other word processors will have equivalent
791options.  Text editors such as the <TT>vi</TT> and <TT>emacs</TT> editors on
792Unix and Linux, Windows Notepad, the <TT>SimpleText</TT> editor in MacOS, or the <TT>pico</TT>
793editor that comes with the <TT>pine</TT>
794mailer program, produce their files in Text Only format and should not
795cause any trouble.
796<P>
797<H3>Input and output files</H3>
798<P>
799For most of the PHYLIP programs, information comes from a series of
800input files, and ends up in a series of output files:
801<P>
802<DIV ALIGN="CENTER">
803<TABLE>
804<TR><TD>
805<PRE>
806                   -------------------
807                  |                   |
808infile ---------> |                   |
809                  |                   |
810intree ---------> |                   | -----------> outfile
811                  |                   |
812weights --------> |      program      | -----------> outtree
813                  |                   |
814categories -----> |                   | -----------> plotfile
815                  |                   |
816fonftile -------> |                   |
817                  |                   |
818                   -------------------
819</PRE>
820</TD></TR>
821</TABLE>
822</DIV><P></P>
823
824<P>
825The programs interact with the user by presenting a menu.  Aside from the
826user's choices from the menu, they read
827all other input from files.  These files have default names.  The program
828will try to find a file of that name - if it does not, it will ask the
829user to supply the name of that file.
830Input data such as DNA sequences
831comes from a file whose default name is <TT>infile</TT>.  If the user
832supplies a tree, this is in a file whose default name is <TT>intree</TT>.
833Values of weights for the characters are in <TT>weights</TT>, and the
834tree plotting program need some digitized fonts which are supplied in
835<TT>fontfile</TT> (all these are default names).
836<P>
837For example, if DnaML looks
838for the file <TT>infile</TT> and does not find one of that name,
839it prints the message:
840<P>
841<TABLE><TR><TD BGCOLOR=white>
842<TT>dnaml: can't find input file "infile"<BR>
843Please enter a new file name></TT>
844</TD></TR></TABLE>
845<P>
846This simply means that it wants you to type in the name of the
847input file.
848<P>
849Two programs in the package works differently according to an older ("Old
850Style") system.  These are <TT>CLIQUE</TT> and <TT>FACTOR</TT>.   The information on ancestral
851states is supplied in the data file whose
852default name is <TT>infile</TT>, and for <TT>FACTOR</TT> the Factors
853information is written into the output file rather than being put into a
854separate file called <TT>factors</TT>.   See the <A HREF="clique.html">documentation
855page for <TT>CLIQUE</TT></A>
856and the <A HREF="factor.html">documentation page for FACTOR</A>
857for information on these differences.  By the time of the final 3.6
858release we hope to have these last Old Style programs converted to the new
859system.
860<P>
861<H3>Data file format</H3>
862<P>
863I have tried to adhere to a rather stereotyped input and output
864format.  For the parsimony, compatibility and maximum likelihood programs,
865excluding the distance matrix methods, the simplest version of the input
866data file looks something like this:
867<P>
868<TABLE><TR><TD BGCOLOR=white>
869<PRE>
870   6   13
871Archaeopt CGATGCTTAC CGC
872HesperorniCGTTACTCGT TGT
873BaluchitheTAATGTTAAT TGT
874B. virginiTAATGTTCGT TGT
875BrontosaurCAAAACCCAT CAT
876B.subtilisGGCAGCCAAT CAC
877</TD></TR></TABLE>
878</PRE>
879<P>
880The first line of the input file contains the number of species and the
881number of characters (in this case sites).  These are in free format, separated
882by blanks.  The information for each species follows, starting with a
883ten-character species name (which can include blanks and some punctuation
884marks), and continuing with the characters for that species.  The name should
885be on the same line as the first character of the data for that species.
886(I will use the term "species" for the tips of the trees, recognizing
887that in some cases these will actually be populations or individual gene
888sequences).
889<P>
890The name should be ten characters in length, filled out to the full
891ten characters by blanks if shorter.  Any printable ASCII/ISO character is
892allowed in the name, except for parentheses ("<TT>(</TT>" and "<TT>)</TT>"), square
893brackets ("<TT>[</TT>" and "<TT>]</TT>"), colon ("<TT>:</TT>"), semicolon ("<TT>;</TT>") and comma ("<TT>,</TT>").
894If you forget to extend the names to ten characters in length by blanks,
895the program will get out of synchronization with the contents of the data
896file, and an error message will result.
897<P>
898In the
899discrete-character programs, DNA sequence programs and protein sequence
900programs the characters are each a
901single letter or digit, sometimes separated by blanks.  In
902the continuous-characters programs they are real numbers with decimal points,
903separated by blanks:
904<P>
905<TT>Latimeria  2.03  3.457  100.2  0.0  -3.7</TT>
906<P>
907The conventions about continuing the data beyond one line per species are
908different between the molecular sequence programs and the others.  The
909molecular sequence programs can take the data in "aligned" or "interleaved"
910format, in which we first have some lines giving the first part of each of the
911sequences, then some
912lines giving the next part of each, and so on.  Thus the sequences might
913look like this:
914<P>
915<TABLE><TR><TD BGCOLOR=white>
916<PRE>
917    6   39
918Archaeopt CGATGCTTAC CGCCGATGCT
919HesperorniCGTTACTCGT TGTCGTTACT
920BaluchitheTAATGTTAAT TGTTAATGTT
921B. virginiTAATGTTCGT TGTTAATGTT
922BrontosaurCAAAACCCAT CATCAAAACC
923B.subtilisGGCAGCCAAT CACGGCAGCC
924
925TACCGCCGAT GCTTACCGC
926CGTTGTCGTT ACTCGTTGT
927AATTGTTAAT GTTAATTGT
928CGTTGTTAAT GTTCGTTGT
929CATCATCAAA ACCCATCAT
930AATCACGGCA GCCAATCAC
931</PRE>
932</TD></TR></TABLE>
933<P>
934Note that in these sequences we have a blank every
935ten sites to make them easier to read: any such blanks are allowed.  The blank
936line which separates the two groups of lines (the ones
937containing sites 1-20 and ones containing sites 21-39) may or may not
938be present, but if it is, it should be a line of zero length and not contain
939any extra blank
940characters (this is because of a limitation of the current versions
941of the programs).  It is important that the number of sites in each
942group be the same for all species (i.e., it will not be possible to run
943the programs successfully if the first species line contains 20 bases, but
944the first line for the second species contains 21 bases).
945<P>
946Alternatively, an option can be selected in the menu to take the data in
947"sequential" format, with all of the data for the first species,
948then all of the characters for the next species, and so on.  This is also
949the way that the discrete characters programs and the gene frequencies
950and quantitative characters programs want to read the data.  They do not
951allow the interleaved format.
952<P>
953In the sequential format, the character data can run on to a new line at any
954time (except in the middle of a species name or, in the case of continuous
955character and distance matrix programs where you cannot go to a new line in
956the middle of a real number).  Thus it is legal to have:
957<P>
958<TT>Archaeopt 001100
959<BR>
9601101
961<BR>
962</TT>
963<P>
964or even:
965<P>
966<TT>Archaeopt
967<BR>
9680011001101
969<BR>
970</TT>
971
972<P>
973though note that the <I>full</I> ten characters of the species name <I>must</I>
974then be present: in the above case there must be a blank after the "t".  In all
975cases it is possible to put internal blanks between any of the character
976values, so that
977<P>
978<TT>Archaeopt 0011001101 0111011100
979</TT>
980<P>
981is allowed.
982<P>
983Note that you can convert molecular sequence data between the interleaved
984and the sequential data formats by using the Rewrite option of the D
985menu item in SEQBOOT.
986<P>
987If you make an error in the format of the input file, the programs can
988sometimes detect that
989they have been fed an illegal character or illegal numerical value and issue
990an error message such as <TT>BAD CHARACTER STATE:</TT>, often printing out the
991bad value, and sometimes the number of the species and character in which it
992occurred.  The program will then stop shortly after.  One of the things which
993can lead to a bad value is the omission of something earlier in the file, or
994the insertion of something superfluous, which cause the reading of the file to
995get out of synchronization.  The program then starts reading things it
996didn't expect, and concludes that they are in error.  So if you see this error
997message, you may also want
998to look for the earlier problem that may have led to the program becoming
999confused about what it is reading.
1000<P>
1001Some options are described below, but you should also read the documentation
1002for the groups of the programs and for the individual programs.
1003<BR>
1004<P>
1005<A NAME="menu"><HR><P></A>
1006<H3>The Menu</H3>
1007<P>
1008The menu is straightforward.  It typically looks like this (this one is for
1009DNAPARS):
1010<P>
1011<TABLE><TR><TD BGCOLOR=white>
1012<PRE>
1013DNA parsimony algorithm, version 3.6
1014
1015Setting for this run:
1016  U                 Search for best tree?  Yes
1017  S                        Search option?  More thorough search
1018  V              Number of trees to save?  100
1019  J   Randomize input order of sequences?  No. Use input order
1020  O                        Outgroup root?  No, use as outgroup species  1
1021  T              Use Threshold parsimony?  No, use ordinary parsimony
1022  N           Use Transversion parsimony?  No, count all steps
1023  W                       Sites weighted?  No
1024  M           Analyze multiple data sets?  No
1025  I          Input sequences interleaved?  Yes
1026  0   Terminal type (IBM PC, ANSI, none)?  (none)
1027  1    Print out the data at start of run  No
1028  2  Print indications of progress of run  Yes
1029  3                        Print out tree  Yes
1030  4          Print out steps in each site  No
1031  5  Print sequences at all nodes of tree  No
1032  6       Write out trees onto tree file?  Yes
1033
1034  Y to accept these or type the letter for one to change
1035</PRE>
1036</TD></TR></TABLE>
1037<P>
1038If you want to accept the default settings (they are shown in the above case)
1039you can simply type <TT>Y</TT> followed by pressing on the <TT>Enter</TT> key.
1040If you want to change any of the options, you should type the letter
1041shown to the left of its entry in the menu.  For example, to set a threshold
1042type <TT>T</TT>.  Lower-case letters will also work.  For many of the options
1043the program will ask for supplementary information, such as the value of
1044the threshold.
1045<P>
1046Note the <TT>Terminal type</TT> entry, which you will find on all menus.  It
1047allows you to specify which type of terminal your screen is.  The options
1048are an IBM PC screen, an ANSI standard terminal, or <TT>none</TT>.
1049Choosing zero (<TT>0</TT>) toggles
1050among these three options in cyclical order, changing each time the <TT>0</TT>
1051option is chosen.  If one of them is right for your terminal the screen will be
1052cleared before the menu is displayed.  If none works, the <TT>none</TT> option
1053should probably be chosen.  The programs should start with a terminal option
1054appropriate for your computer, but if they do not, you can change the
1055terminal type manually.  This is particularly important in program RETREE
1056where a tree is displayed on the screen - if the terminal type is set to the
1057wrong value, the tree can look very strange.
1058<P>
1059The other numbered options control which information the program will
1060display on your screen or on the output files.  The option to <TT>Print
1061indications of progress of run</TT> will show information such as the names of
1062the species as they are successively added to the tree, and the
1063progress of rearrangements.  You will usually want to see these as
1064reassurance that the program is running and to help you estimate how long
1065it will take.  But if you are running the program "in background" as can be
1066done on multitasking and multiuser systems, and do not have the
1067program running in its own window, you may want to turn this option off so
1068that it does not disturb your use of the computer while the program is
1069running.
1070<P>
1071<A NAME="outputfile"><HR><P></A>
1072<H2>The Output File</H2>
1073<BR>
1074<P>
1075Most of the programs write their output onto a file called (usually) <TT>outfile</TT>, and a representation of the trees found onto a file called
1076<TT>outtree</TT>.
1077<P>
1078The exact contents of the output file vary from program to program and also
1079depend on which menu options you have selected.  For many programs, if you
1080select all possible output information, the output will consist of
1081(1) the name of the program and its
1082version number, (2) some of the input information printed out, and (3) a series of
1083phylogenies, some with associated information indicating how much change
1084there was in each character or on each part of the tree.  A typical rooted tree
1085looks like this:
1086<P>
1087<TABLE><TR><TD BGCOLOR=white>
1088<PRE>
1089                                     +-------------------Gibbon
1090        +----------------------------2
1091        !                            !      +------------------Orang
1092        !                            +------4
1093        !                                   !  +---------Gorilla
1094  +-----3                                   +--6
1095  !     !                                      !    +---------Chimp
1096  !     !                                      +----5
1097--1     !                                           +-----Human
1098  !     !
1099  !     +-----------------------------------------------Mouse
1100  !
1101  +------------------------------------------------Bovine
1102</PRE>
1103</TD></TR></TABLE>
1104<P>
1105The interpretation of the tree is fairly straightforward: it "grows"
1106from left to right.  The numbers at the forks are arbitrary and are used (if
1107present) merely to identify the forks.  For many of the programs the tree
1108produced is unrooted.   Rooted and unrooted trees are printed in nearly the
1109same form, but the unrooted ones are accompanied by the
1110warning message:
1111<P>
1112<TT>   remember: this is an unrooted tree!
1113</TT>
1114<P>
1115to indicate that this is an unrooted tree and to warn against
1116taking the position of its root too seriously.  Mathematicians still call
1117an unrooted tree a tree, though some systematists unfortunately use the term
1118"network" for an unrooted tree.  This conflicts with standard mathematical
1119usage, which reserves the name "network" for a completely different kind of
1120graph).  The root of this tree could be anywhere, say on the line leading
1121immediately to <TT>Mouse</TT>.  As an exercise,
1122see if you can tell whether the following tree is or is not a different
1123one from the above:
1124<P>
1125<TABLE><TR><TD BGCOLOR=white>
1126<PRE>
1127             +-----------------------------------------------Mouse
1128             !
1129   +---------4                                   +------------------Orang
1130   !         !                            +------3
1131   !         !                            !      !       +---------Chimp
1132---6         +----------------------------1      !  +----2
1133   !                                      !      +--5    +-----Human
1134   !                                      !         !
1135   !                                      !         +---------Gorilla
1136   !                                      !
1137   !                                      +-------------------Gibbon
1138   !
1139   +-------------------------------------------Bovine
1140
1141   remember: this is an unrooted tree!
1142</PRE>
1143</TD></TR></TABLE>
1144<P>
1145(it is <I>not</I> different).  It is <I>important</I> also to realize that the
1146lengths of the segments of the printed tree may not be significant: some
1147may actually represent branches of zero length, in the sense that there is no
1148evidence that
1149those branches are nonzero in length.  Some of the diagrams of trees attempt
1150to print branches approximately proportional to estimated
1151branch lengths, while in others the lengths are purely conventional and
1152are presented just to make the topology visible.  You will have to look closely
1153at the documentation that accompanies each program to see what it presents
1154and what is known about the lengths of the branches on the tree.  The above
1155tree attempts to represent branch lengths approximately in the diagram.  But
1156even in those cases, some of the smaller branches are likely to be
1157artificially lengthened to make the tree topology clearer.  Here is what
1158a tree from DNAPARS looks like, when no attempt is made to make the
1159lengths of branches in the diagram proportional to estimated branch
1160lengths:
1161<P>
1162<TABLE><TR><TD BGCOLOR=white>
1163<PRE>
1164                 +--Human
1165              +--5
1166           +--4  +--Chimp
1167           !  !
1168        +--3  +-----Gorilla
1169        !  !
1170     +--2  +--------Orang
1171     !  !
1172  +--1  +-----------Gibbon
1173  !  !
1174--6  +--------------Mouse
1175  !
1176  +-----------------Bovine
1177
1178  remember: this is an unrooted tree!
1179</PRE>
1180</TD></TR></TABLE>
1181<P>
1182When a tree has branch lengths, it will be accompanied by a table showing
1183for each branch the numbers (or names) of the nodes at each end of the
1184branch, and the length of that branch.  For the first tree shown above,
1185the corresponding table is:
1186<P>
1187<TABLE><TR><TD BGCOLOR=white>
1188<PRE>
1189 Between        And            Length      Approx. Confidence Limits
1190 -------        ---            ------      ------- ---------- ------
1191
1192    1          Bovine            0.90216     (  0.50346,     1.30086) **
1193    1          Mouse             0.79240     (  0.42191,     1.16297) **
1194    1             2              0.48553     (  0.16602,     0.80496) **
1195    2             3              0.12113     (     zero,     0.24676) *
1196    3             4              0.04895     (     zero,     0.12668)
1197    4             5              0.07459     (  0.00735,     0.14180) **
1198    5          Human             0.10563     (  0.04234,     0.16889) **
1199    5          Chimp             0.17158     (  0.09765,     0.24553) **
1200    4          Gorilla           0.15266     (  0.07468,     0.23069) **
1201    3          Orang             0.30368     (  0.18735,     0.41999) **
1202    2          Gibbon            0.33636     (  0.19264,     0.48009) **
1203
1204      *  = significantly positive, P < 0.05
1205      ** = significantly positive, P < 0.01
1206</PRE>
1207</TD></TR></TABLE>
1208<P>
1209Ignoring the asterisks and the approximate confidence limits, which will be
1210described in the documentation file for DNAML, we can see that the table
1211gives a more precise idea of what the lengths of all the branches are.
1212Similar tables exist in distance matrix and likelihood programs, as well
1213as in the parsimony programs DNAPARS and PARS.
1214<P>
1215Some of the parsimony programs in the package can print out a table
1216of the number of steps that different characters (or sites) require on
1217the tree.  This table may not be obvious at first.  A typical example looks like
1218this:
1219<P>
1220<TABLE><TR><TD BGCOLOR=white>
1221<PRE>
1222 steps in each site:
1223         0   1   2   3   4   5   6   7   8   9
1224     *-----------------------------------------
1225    0!       2   2   2   2   1   1   2   2   1
1226   10!   1   2   3   1   1   1   1   1   1   2
1227   20!   1   2   2   1   2   2   1   1   1   2
1228   30!   1   2   1   1   1   2   1   3   1   1
1229   40!   1
1230</PRE>
1231</TD></TR></TABLE>
1232<P>
1233The numbers across the top and down the side indicate which site
1234is being referred to.  Thus site 23 is column "3" of row "20"
1235and has 1 step in this case.
1236<P>
1237There are many other kinds of information that can appear in the
1238output file,  They vary from program to program, and we leave their
1239description to the documentation files for the specific programs.
1240<P>
1241<A NAME="treefile"><HR><P></A>
1242<H2>The Tree File</H2>
1243<P>
1244In output from most programs,
1245a representation of the tree is also written into the tree file
1246<TT>outtree</TT>.  The tree is specified by nested pairs
1247of parentheses, enclosing
1248names and separated by commas.  We will describe how this works
1249below.  If there are any blanks in the names,
1250these must be replaced by the underscore character "<TT>_</TT>".  Trailing blanks
1251in the name may be omitted.  The pattern of the parentheses indicates
1252the pattern of the tree by having each pair of parentheses enclose all
1253the members of a monophyletic group.  The tree file could look like this:
1254<P>
1255<TT>((Mouse,Bovine),(Gibbon,(Orang,(Gorilla,(Chimp,Human)))));
1256</TT>
1257<P>
1258In this tree the first fork separates the lineage leading to
1259<TT>Mouse</TT> and <TT>Bovine</TT> from the lineage leading to the rest.  Within the
1260latter group there is a fork separating <TT>Gibbon</TT> from the rest, and so on.
1261The entire tree is enclosed in an outermost pair of parentheses.  The tree ends
1262with a semicolon.  In some programs such as DNAML, FITCH, and CONTML,
1263the tree will be unrooted.  An unrooted tree should have its
1264bottommost fork have a
1265three-way split, with three groups separated by two commas:
1266<P>
1267<TT>(A,(B,(C,D)),(E,F));
1268</TT>
1269<P>
1270Here the three groups at the bottom node are <TT>A</TT>, <TT>(B,C,D)</TT>, and
1271<TT>(E,F)</TT>.  The single three-way split corresponds to one of the interior
1272nodes of the unrooted tree (it can be any interior node of the tree).  The
1273remaining forks are encountered as you move out from that first node.
1274In newer programs, some are able to tolerate these other forks being
1275multifurcations (multi-way splits).
1276You should check the documentation files
1277for the particular programs you are using to see in which of these forms
1278you can expect the user tree to be in.  Note that many of the programs
1279that actually estimate an unrooted tree (such as DNAPARS) produce trees in the
1280treefile in rooted form!  This is done for reasons of arbitrary internal bookkeeping.  The placement of the root is arbitrary.  We are working toward
1281having all programs be able to read all trees, whether rooted or unrooted,
1282multifurcating or bifurcating, and having them do the right thing with
1283them.  But this is a long-term goal and it is not yet achieved.
1284<P>
1285For programs that infer branch lengths, these are given in the trees in the
1286tree file as real numbers following a colon, and placed immediately
1287after the group descended from that branch.  Here is a typical tree
1288with branch lengths:
1289<P>
1290<TT>((cat:47.14069,(weasel:18.87953,((dog:25.46154,(raccoon:19.19959,<BR>
1291bear:6.80041):0.84600):3.87382,(sea_lion:11.99700,<BR>
1292seal:12.00300):7.52973):2.09461):20.59201):25.0,monkey:75.85931);
1293</TT>
1294<P>
1295Note that the tree may continue to a new line at any time except in the
1296middle of a name or the middle of a branch length, although in trees
1297written to the tree file this will only be done after a comma.
1298<P>
1299These representations of trees are a subset of the standard adopted
1300on 24 June 1986 at the annual meetings of the Society for the Study of
1301Evolution by an informal committee (its final session in Newick's
1302lobster restaurant - hence its name, the Newick standard)
1303consisting of Wayne Maddison (author of MacClade), David Swofford (PAUP),
1304F. James Rohlf (NTSYS-PC), Chris Meacham (COMPROB and the original
1305PHYLIP tree drawing programs), James Archie,
1306William H.E. Day, and me.  This standard is a generalization of
1307PHYLIP's format, itself based on a well-known representation of trees in
1308terms of parenthesis patterns which is due to the famous mathematician
1309Arthur Cayley, and which has been around for over a century.  The
1310standard is now employed by most phylogeny computer programs but unfortunately
1311has yet to be decribed in a formal published description.  Other
1312descriptions by me and by Gary Olsen can be accessed using the Web at:
1313<P>
1314<DIV ALIGN="CENTER">
1315<FONT SIZE=+2><A HREF="http://evolution.gs.washington.edu/phylip/newicktree.html">
1316<TT>http://evolution.gs.washington.edu/phylip/newicktree.html</TT></A></FONT>
1317</DIV>
1318<P>
1319<A NAME="options"><HR><P></A>
1320<H2>The Options and How To Invoke Them</H2>
1321<P>
1322Most of the programs allow various options that alter the amount of
1323information the program is provided or what is done with the
1324information.  Options are selected in the menu.
1325<P>
1326<H3>Common options in the menu</H3>
1327<P>
1328A number of the options from the menu, the <TT>U</TT> (User tree), <TT>G</TT> (Global),
1329<TT>J</TT> (Jumble), <TT>O</TT> (Outgroup), <TT>W</TT> (Weights),
1330<TT>T</TT> (Threshold), <TT>M</TT> (multiple data sets), and the tree output options, are used
1331so widely that it is best to discuss them in this document.
1332<P>
1333<B>The <TT>U</TT> (User tree) option.</B>  This option toggles between the default
1334setting, which allows the program to search for the best tree, and the
1335User tree setting, which reads a tree or trees ("user trees") from the input
1336tree file and evaluates them.  The input tree file's
1337default name is <TT>intree</TT>.  In a few cases the trees should
1338be preceded by a line giving the number of trees:
1339<P>
1340<TABLE><TR><TD BGCOLOR=white>
1341<PRE>
1342   3
1343((Alligator,Bear),((Cow,(Dog,Elephant)),Ferret));
1344((Alligator,Bear),(((Cow,Dog),Elephant),Ferret));
1345((Alligator,Bear),((Cow,Dog),(Elephant,Ferret)));
1346</PRE>
1347</TD></TR></TABLE>
1348<P>
1349while in most cases the initial line with the number of trees is not
1350required.  This is an inconsistency in the programs that we are intending
1351to eliminate soon.  Some programs require rooted trees, some unrooted
1352trees, and some can handle multifurcating trees.  You should read
1353the documentation for the particular program to find out which it
1354requires.  Program RETREE can be used to convert trees among
1355these forms (on saving a tree from RETREE, you are asked whether
1356you want it to be rooted or unrooted).
1357<P>
1358In using the user tree option, check the pattern of parentheses
1359carefully.  The programs do not always detect
1360whether the tree makes sense, and if it does not there will probably be
1361a crash (hopefully, but not inevitably, with an error message indicating
1362the nature of the problem).  Trees written out by programs are
1363typically in the proper form.
1364<P>
1365Some of the programs require that the user trees be preceded by line with the
1366number of user trees.  Some require that they <EM>not</EM> be preceded by
1367this line, and many can tolerate either.  I have tried to note for
1368each of these programs which of these forms of the user tree file
1369is appropriate.  We hope to bring all programs to the same user tree file
1370format as soon as possible.
1371<P>
1372<B>The <TT>G</TT> (Global) option.</B>  In  the programs which construct trees (except for
1373NEIGHBOR, the "...PENNY" programs and CLIQUE, and of course
1374the "...MOVE" programs where you construct the trees yourself),
1375after all species have been added to the tree a rearrangements phase
1376ensues.  In most of these programs the rearrangements are automatically
1377global, which in this case means that subtrees will be removed from the tree
1378and put back on in all possible ways so as to have a better chance of
1379finding a better tree.  Since this can be time consuming (it roughly
1380triples the time taken for a run) it is left as an option in some of the
1381programs, specifically CONTML, FITCH, and DNAML.  In these programs
1382the G menu option toggles between the default of local rearrangement and
1383global rearrangement.  The rearrangements are explained more below.
1384<P>
1385<B>The <TT>J</TT> (Jumble) option.</B>  In most of the tree construction programs
1386(except for the "...PENNY" programs and CLIQUE), the exact
1387details of the search of different trees depend on the order of input of
1388species.  In these programs <TT>J</TT> option enables you to tell the program to use
1389a random number
1390generator to choose the input order of species.  This option is toggled on
1391and off by
1392selecting option <TT>J</TT> in the menu.  The program will then prompt you for
1393a "seed" for the random number generator.  The seed should be an integer
1394between 1 and 32767, and should of form 4n+1,
1395which means that it must give a remainder of 1 when divided by 4.  This can be
1396judged by looking at the last two digits of the number.  Each different seed
1397leads to a different sequence of addition of species.  By simply changing the
1398random number seed and re-running the programs one can look for other, and
1399better trees.  If the seed entered is not odd, the program will not proceed,
1400but will prompt for another seed.
1401<P>
1402The Jumble option also causes the program to ask you how many times you
1403want to restart the process.  If you answer 10, the program will
1404try ten different orders of species in constructing the trees, and the
1405results printed out will reflect this entire search process (that is,
1406the best trees found among all 10 runs will be printed out, not the
1407best trees from each individual run).
1408<P>
1409Some people have asked what are good values of the random number seed.
1410The random number seed is used to start a process of choosing "random"
1411(actually pseudorandom) numbers, which behave as if they were
1412unpredictably randomly chosen between 0 and 2<SUP>32</SUP>-1 (which is
14134,294,967,296).  You could put in the number 133 and find that the
1414next random number was 1,876,973,009.  As they are effectively
1415unpredictable, there is no such thing as a choice that is better than
1416any other, provided that the numbers are of the form 4<I>n</I>+1.  However
1417if you re-use a random number seed, the sequence of random numbers
1418that result will be the same as before, resulting in exactly the same
1419series of choices, which may not be what you want.
1420<P>
1421<B>The <TT>O</TT> (Outgroup) option.</B>  This specifies which species is to be used
1422to root the tree by having it become the outgroup.  This option is
1423toggled on and off by choosing <TT>O</TT> in the menu (the alphabetic
1424character <TT>O</TT>, not the digit <TT>0</TT>).  When it is on, the program will
1425then prompt for the
1426number of the outgroup (the species being taken in the numerical order that
1427they occur in the input file).  Responding by typing <TT>6</TT> and then an
1428<TT>Enter</TT> character indicates that the sixth species in the data
1429is the outgroup.  Outgroup-rooting will not be attempted if the
1430data have already established a root for the tree from some other
1431consideration, and may not be if it is a user-defined tree,
1432despite your invoking the option.  Thus programs such as DOLLOP that
1433produce only rooted trees do not allow the Outgroup option.  It is also
1434not available in KITSCH, DNAMLK, or CLIQUE.  When it is used, the tree as
1435printed out is still listed as being an
1436unrooted tree, though the outgroup is connected to the bottommost node
1437so that it is easy to visually convert the tree into rooted form.
1438<P>
1439<B>The <TT>T</TT> (Threshold) option.</B>  This sets a threshold forn the
1440parsimony programs such that if the
1441number of steps counted in a character is higher than the threshold, it
1442will be taken to be the threshold value rather than the actual number of
1443steps.  The default is a threshold so high that it will never be
1444surpassed (in which case the steps whill simply be counted).  The <TT>T</TT>
1445menu option toggles on and off asking the user to
1446supply a threshold.  The use of thresholds to obtain methods intermediate
1447between parsimony and compatibility methods is described in my 1981b paper.
1448When the T option is in force, the program
1449will prompt for the numerical threshold value.  This will be a positive
1450real number greater than 1.  In programs MIX, MOVE, PENNY, PROTPARS,
1451DNAPARS, DNAMOVE, and DNAPENNY, do not use threshold values less
1452than or equal to 1.0, as they have no meaning and lead to a tree which
1453depends only on considerations such as the input order of species and not at
1454all on the character state data!  In programs DOLLOP, DOLMOVE, and DOLPENNY
1455the threshold should never be 0.0 or less, for the same
1456reason.  The <TT>T</TT> option is an
1457important and underutilized one: it is, for example, the only way in this
1458package (except for program DNACOMP) to do a compatibility analysis when there
1459are missing data.   It is a method of de-weighting characters that evolve
1460rapidly.  I wish more people were aware of its properties. 
1461<P>
1462<B>The <TT>M</TT> (Multiple data sets) option.</B>  In menu programs there is an
1463<TT>M</TT> menu
1464option which allows one to toggle on the multiple data sets option.  The
1465program will ask you how many data sets it should expect.  The data sets
1466have the same format as the first data set.  Here is a (very small) input file
1467with two five-species data sets:
1468<P>
1469<TABLE><TR><TD bgcolor=white>
1470<PRE>
1471      5    6
1472Alpha     CCACCA
1473Beta      CCAAAA
1474Gamma     CAACCA
1475Delta     AACAAC
1476Epsilon   AACCCA
14775    6
1478Alpha     CACACA
1479Beta      CCAACC
1480Gamma     CAACAC
1481Delta     GCCTGG
1482Epsilon   TGCAAT
1483</PRE>
1484</TD></TR></TABLE>
1485<P>
1486The main use of this option will be to allow all of the methods in these
1487programs to be bootstrapped.  Using the program SEQBOOT one can take any
1488DNA, protein, restriction sites, gene frequency or binary character data set and
1489make multiple data sets by bootstrapping.  Trees can be produced for all of
1490these using the <TT>M</TT> option.  They will be written on the tree output file if
1491that option is left in force.  Then the program CONSENSE can be used with
1492that tree file as its input file.  The result is a majority rule consensus
1493tree which can be used to make confidence intervals.  The present version
1494of the package allows, with the use of SEQBOOT and CONSENSE and the M option,
1495bootstrapping of many of the methods in the package.
1496<P>
1497Programs DNAML, DNAPARS and PARS can also take multiple weights
1498instead of multiple data sets.  They can then do bootstrapping by
1499reading in one data set, together with a file of weights that show how
1500the characters (or sites) are reweighted in each bootstrap sample.  Thus a
1501site that is omitted in a bootstrap sample has effectively been given
1502weight 0, while a site that has been duplicated has effectively been
1503given weight 2.  SEQBOOT has a menu selection to produce the file of
1504weights information automatically, instead of producing a file of
1505multiple data sets.
1506<P>
1507<B>The <TT>W</TT> (Weights) option</B>.  This signals the program that, in
1508addition to the data set, you want to read in a series of weights that
1509tell how many times each character is to be counted.  If the weight
1510for a character is zero (<TT>0</TT>) then that character is in effect to
1511be omitted when the tree is evaluated.  If it is (<TT>1</TT>) the
1512character is to be counted once.  Some programs allow weights greater than
15131 as well.  These have the effect that the character is counted as
1514if it were present that many times, so that a weight of 4 means that the
1515character is counted 4 times.
1516The values 0-9 give weights 0 through 9, and the
1517values A-Z give weights 10 through 35.  By use of the weights we can
1518give overwhelming weight to some characters, and drop others from the
1519analysis.  In the molecular sequence programs only two values of the
1520weights, 0 or 1 are allowed.
1521<P>
1522The weights are used to analyze subsets of the characters, and also can be
1523used for resampling of the data as in bootstrap and jackknife resampling.
1524For those programs that allow weights to be greater than 1, they can also
1525be used to emphasize information from some characters more strongly than
1526others.  Of course, you must have some rationale for doing this.
1527<P>
1528The weights are provided as a sequence of digits.  Thus they might be
1529<P>
1530<TT>10011111100010100011110001100</TT>
1531<P>
1532The weights are to be provided in an input file
1533whose default name is <TT>weights</TT>.  In programs such as SEQBOOT
1534that can also output a file of weights, the input weights have a default
1535file name of <TT>inweights</TT>, and the output file name has a default
1536file name of <TT>outweights</TT>.
1537<P>
1538Weights can be used to analyze different subsets of characters (by weighting
1539the rest as zero).  Alternatively, in the discrete characters programs
1540they can be used to force a certain
1541group to appear on the phylogeny (in effect confining consideration to only
1542phylogenies containing that group).  This is done by adding an imaginary
1543character that has <TT>1</TT>'s for the members of the group, and <TT>0</TT>'s
1544for all the
1545other species.  That imaginary character is then given the highest weight
1546possible: the result will be that any phylogeny that does not contain that
1547group will be penalized by such a heavy amount that it will not (except in
1548the most unusual circumstances) be considered.  Of course, the new character
1549brings extra steps to the tree, but the number of these can be calculated
1550in advance and subtracted out of the total when reporting the results.  This
1551use of weights is an important one, and one sadly ignored
1552by many users who could profit from it.  In the case of molecular sequences
1553we cannot use weights this way, so that to force a given group to appear we
1554have to add a large extra segment of sites to the molecule, with (say) A's
1555for that group and C's for every other species.
1556<P>
1557<B>The option to write out the trees into a tree file</B>.  This specifies that you
1558want the program to write
1559out the tree not only on its usual output, but also onto a file in
1560nested-parenthesis notation (as described above).  This option is sufficiently
1561useful that it is turned on by default in all programs that allow it.  You
1562can optionally turn it off if you wish, by typing the appropriate number
1563from the menu (it varies from program to program).  This option is useful for
1564creating tree files that can be directly read into the programs, including
1565the consensus tree and tree distance programs, and the tree plotting programs.
1566<P>
1567The output tree file has a default name of <TT>outtree</TT>.
1568<P>
1569<B>The (<TT>0</TT>) terminal type option</B> .  (This is the digit <TT>0</TT>, not
1570the alphabetic character <TT>O</TT>). The program will default to
1571one particular assumption about your terminal (except in the case of
1572Macintoshes, the default will be an ANSI compatible terminal). You can
1573alternatively select it to be either an IBM PC, or nothing.
1574This affects the ability of the programs to clear the screen when they
1575display their menus, and the graphics characters used to display trees
1576in the programs DNAMOVE, MOVE, DOLMOVE, and RETREE.  If you are running an
1577MSDOS system and have the ANSI.SYS driver installed in your CONFIG.SYS
1578file, you may find that the screen clears correctly even with the default
1579setting of ANSI.
1580<P>
1581<A NAME="algorithm"><HR><P></A>
1582<DIV ALIGN="CENTER">
1583<H2>The Algorithm for Constructing Trees</H2></DIV>
1584<P>
1585All of the programs except FACTOR, DNADIST, GENDIST, DNAINVAR, SEQBOOT,
1586CONTRAST, RETREE, and the plotting and
1587consensus tree programs act to construct an estimate of a phylogeny.  MOVE,
1588DOLMOVE, and DNAMOVE let you construct it yourself by hand.  All of
1589the rest but NEIGHBOR, the "...PENNY" programs and CLIQUE make use of
1590a common approach involving additions and rearrangements.  They are
1591trying to minimize or maximize some quantity over the space of all
1592possible evolutionary trees.  Each program contains a part that, given
1593the topology of the tree, evaluates the quantity that is being minimized
1594or maximized.  The straightforward approach would be to evaluate all
1595possible tree topologies one after another and pick the one which,
1596according to the criterion being used, is best.  This would not be
1597possible for more than a small number of species, since the number of
1598possible tree topologies is enormous.  A review of the literature on the
1599counting of evolutionary trees will be found one of my papers
1600(Felsenstein, 1978a).
1601<P>
1602Since we cannot search all topologies, these programs are not
1603guaranteed to always find the best tree, although they seem to do quite
1604well in practice.  The strategy they employ is as follows: the species
1605are taken in the order in which they appear in the input file.  The
1606first two (in some programs the first three) are taken and a tree
1607constructed containing only those.  There is only one possible topology for
1608this tree.  Then the next species is taken, and we consider where it
1609might be added to the tree.  If the initial tree is (say) a rooted tree
1610with two species and we want the resulting three-species tree to be a
1611bifurcating tree, there are only three places where we could add the
1612third species.  Each of these is tried, and each time the resulting tree is
1613evaluated according to the criterion.  The best one is chosen to be the
1614basis for further operations.  Now we consider adding the fourth
1615species, again at each of the five possible places that would result in
1616a bifurcating tree.  Again, the best of these is accepted.
1617<P>
1618<H3>Local Rearrangements</H3>
1619<P>
1620The process continues in this manner, with one important exception.  After
1621each species is added, and before the next
1622is added, a number of rearrangements of the tree are tried, in an effort
1623to improve it.  The algorithms move through the tree, making all
1624possible local rearrangements of the tree.  A local rearrangement involves an
1625internal segment of the tree in the following manner.  Each internal
1626segment of the tree is of this form (where T1, T2, and T3 are subtrees
1627- parts of the tree that can contain further forks and tips):
1628<P>
1629<PRE>
1630            T1      T2       T3
1631             \      /        /
1632              \    /        /
1633               \  /        /
1634                \/        /
1635                 *       /
1636                  *     /
1637                   *   /
1638                    * /
1639                     *
1640                     !
1641                     !
1642</PRE>
1643<P>
1644the segment we are discussing being indicated by the asterisks.  A local
1645rearrangement consists of switching the subtrees T1 and T3 or T2 and T3,
1646so as to obtain one of the following:
1647<P>
1648<PRE>
1649          T3       T2      T1            T1       T3      T2
1650           \       /       /              \       /       /
1651            \     /       /                \     /       /
1652             \   /       /                  \   /       /
1653              \ /       /                    \ /       /
1654               \       /                      \       /
1655                \     /                        \     /
1656                 \   /                          \   /
1657                  \ /                            \ /
1658                   !                              !
1659                   !                              !
1660                   !                              !
1661</PRE>
1662<P>
1663Each time a local rearrangement is successful in finding a better tree,
1664the new arrangement is accepted.  The phase of local rearrangements does
1665not end until the program can traverse the entire tree, attempting local
1666rearrangements, without finding any that improve the tree.
1667<P>
1668This strategy of adding species and making local rearrangements will look
1669at about &nbsp;(n-1)x(2n-3)&nbsp; different topologies, though if
1670rearrangements are frequently successful the number may be larger.  I
1671have been describing the strategy when rooted trees are being
1672considered.  For unrooted trees there is a precisely similar strategy,
1673though the first tree constructed may be a three-species tree and the
1674rearrangements may not start until after the addition of the fifth
1675species.
1676<P>
1677Though we are not guaranteed to have found the best tree topology,
1678we are guaranteed that no nearby topology (i. e.  none accessible by a
1679single local rearrangement) is better.  In this sense we have reached a
1680local optimum of our criterion.  Note that the whole process is
1681dependent on the order in which the species are present in the input
1682file.  We can try to find a different and better solution by reordering
1683the species in the input file and running the program again (or, more
1684easily, by using the <TT>J</TT> option).  If none of
1685these attempts finds a better solution, then we have some indication
1686that we may have found the best topology, though we can never be certain
1687of this.
1688<P>
1689Note also that a new topology is never accepted unless it is better
1690than the previous one, so that the rearrangement process can never fall
1691into an endless loop.  This is also the way ties in our criterion are
1692resolved, namely by sticking with the tree found first.  However, the tree
1693construction programs other than CLIQUE, CONTML, FITCH,
1694and DNAML do keep a record of all trees found that are tied with the best one
1695found.  This gives you some immediate idea of which parts of the tree can be
1696altered without affecting the quality of the result.
1697<P>
1698
1699<H3>Global Rearrangements</H3>
1700<P>
1701A feature of most of the programs, such as PROTPARS, DNAPARS,
1702DNACOMP, DNAML, DNAMLK, RESTML, KITSCH, FITCH, CONTML, MIX, and DOLLOP,
1703is "global" optimization of the tree.  In four of these (CONTML,
1704FITCH, DNAML and DNAMLK) this is an option, <TT>G</TT>.  In the others it
1705automatically applies.  When
1706it is present there is an additional stage to the search for the best tree. 
1707Each possible subtree is removed from the tree from the tree and added back in
1708all possible places.  This process continues until all subtrees can be removed
1709and added again without any improvement in the tree.  The purpose of this
1710extra rearrangement is to make it less likely that one or more a species gets
1711"stuck" in a suboptimal region of the space of all possible trees.  The use of
1712global optimization results in approximately a tripling (3 x ) of the run-time,
1713which is why I have left it as an option in some of the slower programs.
1714<P>
1715What PHYLIP calls "global" rearrangements are more properly called
1716SPR (subtree pruning and regrafting) by Swofford et. al. (1996) as distinct
1717from the NNI (nearest neighbor interchange) rearrangements that PHYLIP
1718also uses, and the TBR (tree bisection and reconnection) rearrangements
1719that it does not use.
1720<P>
1721The programs doing global optimization print out a dot "<TT>.</TT>" after each group is
1722removed and re-added to the tree, to give the user some sign that the
1723rearrangements are proceeding.  A new line of dots is started whenever a new
1724round of global rearrangements is started following an improvement in the
1725tree.  On the line before the dots are printed there is printed a bar of
1726the form "!---------------!" to show how many dots
1727to expect.  The dots will
1728not be printed out at a uniform rate, but the later dots, which represent
1729removal of larger groups from the tree and trying them consequently in fewer
1730places, will print out more quickly.  With some compilers each row of dots may
1731not be printed out until it is complete.
1732<P>
1733It should be noted that PENNY, DOLPENNY, DNAPENNY and CLIQUE use a more
1734sophisticated strategy of "depth-first search" with a "branch and bound"
1735search method that guarantees that all
1736of the best trees will be found.  In the case
1737of PENNY, DOLPENNY and DNAPENNY there can be a considerable sacrifice of
1738computer time if the number of species is greater than about ten: it is a
1739matter for you to consider whether it is worth it for you to guarantee finding
1740all the most parsimonious trees, and that depends on how much free computer
1741time you have!  CLIQUE finds all largest cliques, and does so without undue
1742burning of computer time.   Although all of these problems that have been
1743investigated fall into the
1744category of "NP-hard" problems that in effect do not have a rapid solution,
1745the cases that cause this trouble for the largest-cliques algorithm in
1746CLIQUE apparently are not biologically realistic and do not occur in actual
1747data.
1748<P>
1749
1750<H3>Multiple Jumbles</H3>
1751<P>
1752As just mentioned, for most of these programs the search depends on the order
1753in which the species are entered into the tree.  Using the <TT>J</TT> (Jumble)
1754option you can supply a random number seed which will allow the program to put
1755the species in in a random order.  Jumbling can be
1756done multiple times.  For example, if you tell the program to do it
175710 times, it will go through the tree-building process 10 times, each with a
1758different random order of adding species.  It will keep a record of the trees
1759tied for best over the whole process.  In other words, it does not just
1760record the best trees from each of the 10 runs, but records the best ones
1761overall.  Of course this is slow, taking 10 times longer than a single run.
1762But it does give us a much greater chance of finding all of the most
1763parsimonious trees.  In the terminology of Maddison (1991) it
1764can find different "islands" of trees.  The present algorithms do not
1765guarantee us to find all trees in a given "island" from a single run, so
1766multiple runs also help explore those "islands" that are found.
1767<P>
1768<H3>Saving multiple tied trees</H3>
1769<P>
1770For the parsimony and compatibility programs, one can have a perfect tie
1771between two or more trees.  In these programs these trees are all
1772saved.  For the newer parsimony programs such as DNAPARS and PARS,
1773global rearrangement is carried out on all of these tied trees.  This can
1774be turned off in the menu.
1775<P>
1776For trees with criteria which are real numbers, such as the distance
1777matrix programs FITCH and KITSCH, and the likelihood programs DNAML,
1778DNAMLK, CONTML, and RESTML, it is difficult to get an exact tie between
1779trees.  Consequently these programs save only the single best tree
1780(even though the others may be only a tiny bit worse).
1781<P>
1782<H3>Strategy for Finding the Best Tree</H3>
1783<P>
1784In practice, it is advisable to use the Jumble option to evaluate many
1785different orderings of the input species.  <I>It is advisable to use the
1786Jumble option and specify that it be done many times (as many as ten)</I>
1787to use different orderings
1788of the input species).
1789<P>
1790People who want a magic "black box" program whose results they do
1791not have to question (or think about) often are upset that these
1792programs give results that are dependent on the order in which the species
1793are entered in the data.  To me this property is an advantage, for it
1794permits you to try different searches for better trees, simply by
1795varying the input order of species.  If you do not use the multiple Jumble
1796option, but do multiple individual runs instead, you
1797can easily decide which to pay most attention to - the one or ones that
1798are best according to the criterion employed (for example, with parsimony,
1799the one out of the runs that results in the tree with the fewest changes).
1800<P>
1801In practice, in a single run, it usually seems best to put species that are
1802likely to be sources of confusion in the topology last, as by the time they are
1803added the arrangement of the earlier species will have stabilized into a
1804good configuration, and then the last few species will by fitted into
1805that topology.  There will be less chance this way of a poor initial
1806topology that would affect all subsequent parts of the search.  However,
1807a variety of arrangements of the input order of species should be tried,
1808as can be done if the <TT>J</TT> option is used,
1809and no species should be kept in a fixed place in the order of input.
1810Note that the results of the "...PENNY" programs and CLIQUE
1811are not sensitive to the input order of species, and NEIGHBOR is only
1812slightly sensistive to it, so that multiple Jumbling is not possible
1813with those programs.  Note also that with global search, which
1814is standard in many programs and in others is an
1815option, each group (including
1816each individual species) will be removed and re-added in all possible
1817positions, so that a species causing confusion will have more chance of moving
1818to a new location than it would without global rearrangement.
1819<P>
1820<A NAME="warning"><HR><P></A>
1821<DIV ALIGN="CENTER">
1822<H2>A Warning on Interpreting Results</H2></DIV>
1823<P>
1824Probably the most important thing to keep in mind while running any of the
1825parsimony or compatibility programs is not
1826to overinterpret the result.  Many users treat the set of most parsimonious
1827trees as if it were a confidence interval.  If a group appears in all of the
1828most parsimonious trees then they treat it as well established.  Unfortunately
1829<I>the confidence interval on phylogenies appears to be much
1830larger than the set of all most parsimonious trees</I> (Felsenstein, 1985b).
1831Likewise, variation of result among different methods will not be a good
1832indicator of the size of the confidence interval.  Consider a simple data set
1833in which, out of 100 binary characters, 51 recommend the unrooted tree
1834<TT>((A,B),(C,D))</TT> and 49 the tree <TT>((A,D),(B,C))</TT>.  Many different
1835methods will all give the same result on
1836such a data set: they will estimate the tree as <TT>((A,B),(C,D))</TT>.
1837Nevertheless it is
1838clear that the 51:49 margin by which this tree is favored is not statistically
1839significantly different from 50:50.  So <I>consistency among different methods
1840is a poor guide to statistical significance</I>.
1841<P>
1842<A NAME="speed"><HR><P></A>
1843<DIV ALIGN="CENTER">
1844<H2>Relative Speed of Different<BR>
1845Programs and Machines</H2></DIV>
1846<P>
1847<H3>Relative speed of the different programs</H3>
1848<P>
1849C compilers differ in efficiency of the code they generate,
1850and some deal with some features of the language better than with
1851others.  Thus a program which is unusually fast on one computer may be
1852unusually slow on another.  Nevertheless, as a rough guide to relative
1853execution speeds, I have tested the programs on three data sets, each of
1854which has 10 species and 40 characters.  The first is an imaginary one
1855in which all characters are compatible - ("The Willi Hennig Memorial
1856Data Set" as J. S. Farris once called ones like it).  The second is the binary
1857recoded form of the fossil horses data set of Camin and Sokal (1965).
1858The third data set has data that is completely random: 10 species and 20
1859characters that have a 50% chance that each character state is <TT>0</TT> or
1860<TT>1</TT> (or <TT>A</TT> or <TT>G</TT>).  The data sets thus range from a completely
1861compatible one in which there is no homoplasy (paralellism or convergence),
1862through the horses data set, which requires 29 steps where the possible
1863minimum number would be 20, to the random data set, which requires 49 steps. 
1864We can thus see how this increasing messiness of the data affects running
1865times.  The three data sets have all had 20 sites of <TT>A</TT>'s added to the
1866end of each sequence, so as to prevent likelihood or distance matrix programs
1867from having infinite branch lengths (the test data sets used for timing
1868previous versions of PHYLIP wsere the same except that they lacked these
186920 extra sites).
1870<P>
1871Here are the nucleotide sequence versions of the three data sets:
1872<P>
1873<TABLE><TR><TD BGCOLOR=white>
1874<PRE>
1875    10   40
1876A         CACACACAAAAAAAAAAACAAAAAAAAAAAAAAAAAAAAA
1877B         CACACAACAAAAAAAAAACAAAAAAAAAAAAAAAAAAAAA
1878C         CACAACAAAAAAAAAAAACAAAAAAAAAAAAAAAAAAAAA
1879D         CAACAAAACAAAAAAAAACAAAAAAAAAAAAAAAAAAAAA
1880E         CAACAAAAACAAAAAAAACAAAAAAAAAAAAAAAAAAAAA
1881F         ACAAAAAAAACACACAAAACAAAAAAAAAAAAAAAAAAAA
1882G         ACAAAAAAAACACAACAAACAAAAAAAAAAAAAAAAAAAA
1883H         ACAAAAAAAACAACAAAAACAAAAAAAAAAAAAAAAAAAA
1884I         ACAAAAAAAAACAAAACAACAAAAAAAAAAAAAAAAAAAA
1885J         ACAAAAAAAAACAAAAACACAAAAAAAAAAAAAAAAAAAA
1886</PRE>
1887</TD></TR></TABLE>
1888<P>
1889<TABLE><TR><TD BGCOLOR=white>
1890<PRE>
1891    10   40
1892MesohippusAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA
1893HypohippusAAACCCCCCCAAAAAAAAACAAAAAAAAAAAAAAAAAAAA
1894ArchaeohipCAAAAAAAAAAAAAAAACACAAAAAAAAAAAAAAAAAAAA
1895ParahippusCAAACAACAACAAAAAAAACAAAAAAAAAAAAAAAAAAAA
1896MerychippuCCAACCACCACCCCACACCCAAAAAAAAAAAAAAAAAAAA
1897M. secunduCCAACCACCACCCACACCCCAAAAAAAAAAAAAAAAAAAA
1898Nannipus  CCAACCACAACCCCACACCCAAAAAAAAAAAAAAAAAAAA
1899NeohippariCCAACCCCCCCCCCACACCCAAAAAAAAAAAAAAAAAAAA
1900Calippus  CCAACCACAACCCACACCCCAAAAAAAAAAAAAAAAAAAA
1901PliohippusCCCACCCCCCCCCACACCCCAAAAAAAAAAAAAAAAAAAA
1902</PRE>
1903</TD></TR></TABLE>
1904<P>
1905<TABLE><TR><TD BGCOLOR=white>
1906<PRE>
1907    10   40
1908A         CACACAACCAAACAAACCACAAAAAAAAAAAAAAAAAAAA
1909B         AAACCACACACACAAACCCAAAAAAAAAAAAAAAAAAAAA
1910C         ACAAAACCAAACCACCCACAAAAAAAAAAAAAAAAAAAAA
1911D         AAAAACACAACACACCAAACAAAAAAAAAAAAAAAAAAAA
1912E         AAACAACCACACACAACCAAAAAAAAAAAAAAAAAAAAAA
1913F         CCCAAACACCCCCAAAAAACAAAAAAAAAAAAAAAAAAAA
1914G         ACACCCCCACACCCACCAACAAAAAAAAAAAAAAAAAAAA
1915H         AAAACAACAACCACCCCACCAAAAAAAAAAAAAAAAAAAA
1916I         ACACAACAACACAAACAACCAAAAAAAAAAAAAAAAAAAA
1917J         CCAAAAACACCCAACCCAACAAAAAAAAAAAAAAAAAAAA
1918</PRE>
1919</TD></TR></TABLE>
1920<P>
1921Here are the timings of many of the version 3.6 programs on these three data
1922sets as run after being compiled by Gnu C and run on a
1923266 MHz Pentium MMX computer under Linux.
1924<P>
1925<DIV ALIGN="CENTER">
1926<TABLE CELLPADDING=3 BORDER="1">
1927<TR><TD ALIGN="LEFT">&nbsp;</TD>
1928<TD ALIGN="RIGHT">Hennigian Data</TD>
1929<TD ALIGN="RIGHT">Horses Data</TD>
1930<TD ALIGN="RIGHT">Random Data</TD>
1931</TR>
1932<TR><TD ALIGN="LEFT">PROTPARS</TD>
1933<TD ALIGN="RIGHT">0.133</TD>
1934<TD ALIGN="RIGHT">0.167</TD>
1935<TD ALIGN="RIGHT">0.308</TD>
1936</TR>
1937<TR><TD ALIGN="LEFT">DNAPARS</TD>
1938<TD ALIGN="RIGHT">0.163</TD>
1939<TD ALIGN="RIGHT">0.191</TD>
1940<TD ALIGN="RIGHT">0.573</TD>
1941</TR>
1942<TR><TD ALIGN="LEFT">DNAPENNY</TD>
1943<TD ALIGN="RIGHT">0.300</TD>
1944<TD ALIGN="RIGHT">0.196</TD>
1945<TD ALIGN="RIGHT">36.68</TD>
1946</TR>
1947<TR><TD ALIGN="LEFT">DNACOMP</TD>
1948<TD ALIGN="RIGHT">0.081</TD>
1949<TD ALIGN="RIGHT">0.073</TD>
1950<TD ALIGN="RIGHT">0.127</TD>
1951</TR>
1952<TR><TD ALIGN="LEFT">DNAML</TD>
1953<TD ALIGN="RIGHT">2.19</TD>
1954<TD ALIGN="RIGHT">2.53</TD>
1955<TD ALIGN="RIGHT">2.73</TD>
1956</TR>
1957<TR><TD ALIGN="LEFT">DNAMLK</TD>
1958<TD ALIGN="RIGHT">5.40</TD>
1959<TD ALIGN="RIGHT">6.13</TD>
1960<TD ALIGN="RIGHT">7.21</TD>
1961</TR>
1962<TR><TD ALIGN="LEFT">PROML</TD>
1963<TD ALIGN="RIGHT">44.79</TD>
1964<TD ALIGN="RIGHT">90.46</TD>
1965<TD ALIGN="RIGHT">68.49</TD>
1966</TR>
1967<TR><TD ALIGN="LEFT">PROMLK</TD>
1968<TD ALIGN="RIGHT">171.01</TD>
1969<TD ALIGN="RIGHT">183.61</TD>
1970<TD ALIGN="RIGHT">239.34</TD>
1971</TR>
1972<TR><TD ALIGN="LEFT">DNAML</TD>
1973<TD ALIGN="RIGHT">2.19</TD>
1974<TD ALIGN="RIGHT">2.53</TD>
1975<TD ALIGN="RIGHT">2.73</TD>
1976</TR>
1977<TR><TD ALIGN="LEFT">DNAINVAR</TD>
1978<TD ALIGN="RIGHT">0.002</TD>
1979<TD ALIGN="RIGHT">0.002</TD>
1980<TD ALIGN="RIGHT">0.002</TD>
1981</TR>
1982<TR><TD ALIGN="LEFT">DNADIST</TD>
1983<TD ALIGN="RIGHT">0.029</TD>
1984<TD ALIGN="RIGHT">0.024</TD>
1985<TD ALIGN="RIGHT">0.033</TD>
1986</TR>
1987<TR><TD ALIGN="LEFT">PROTDIST</TD>
1988<TD ALIGN="RIGHT">1.095</TD>
1989<TD ALIGN="RIGHT">1.089</TD>
1990<TD ALIGN="RIGHT">1.107</TD>
1991</TR>
1992<TR><TD ALIGN="LEFT">RESTML</TD>
1993<TD ALIGN="RIGHT">3.55</TD>
1994<TD ALIGN="RIGHT">3.18</TD>
1995<TD ALIGN="RIGHT">5.15</TD>
1996</TR>
1997<TR><TD ALIGN="LEFT">RESTDIST</TD>
1998<TD ALIGN="RIGHT">0.012</TD>
1999<TD ALIGN="RIGHT">0.010</TD>
2000<TD ALIGN="RIGHT">0.010</TD>
2001</TR>
2002<TR><TD ALIGN="LEFT">FITCH</TD>
2003<TD ALIGN="RIGHT">0.20</TD>
2004<TD ALIGN="RIGHT">0.31</TD>
2005<TD ALIGN="RIGHT">0.24</TD>
2006</TR>
2007<TR><TD ALIGN="LEFT">KITSCH</TD>
2008<TD ALIGN="RIGHT">0.055</TD>
2009<TD ALIGN="RIGHT">0.061</TD>
2010<TD ALIGN="RIGHT">0.058</TD>
2011</TR>
2012<TR><TD ALIGN="LEFT">NEIGHBOR</TD>
2013<TD ALIGN="RIGHT">0.003</TD>
2014<TD ALIGN="RIGHT">0.004</TD>
2015<TD ALIGN="RIGHT">0.005</TD>
2016</TR>
2017<TR><TD ALIGN="LEFT">CONTML</TD>
2018<TD ALIGN="RIGHT">0.380</TD>
2019<TD ALIGN="RIGHT">0.368</TD>
2020<TD ALIGN="RIGHT">0.396</TD>
2021</TR>
2022<TR><TD ALIGN="LEFT">GENDIST</TD>
2023<TD ALIGN="RIGHT">0.008</TD>
2024<TD ALIGN="RIGHT">0.009</TD>
2025<TD ALIGN="RIGHT">0.008</TD>
2026</TR>
2027<TR><TD ALIGN="LEFT">PARS</TD>
2028<TD ALIGN="RIGHT">0.201</TD>
2029<TD ALIGN="RIGHT">0.263</TD>
2030<TD ALIGN="RIGHT">0.729</TD>
2031</TR>
2032<TR><TD ALIGN="LEFT">MIX</TD>
2033<TD ALIGN="RIGHT">0.064</TD>
2034<TD ALIGN="RIGHT">0.078</TD>
2035<TD ALIGN="RIGHT">0.123</TD>
2036</TR>
2037<TR><TD ALIGN="LEFT">PENNY</TD>
2038<TD ALIGN="RIGHT">0.038</TD>
2039<TD ALIGN="RIGHT">0.087</TD>
2040<TD ALIGN="RIGHT">15.93</TD>
2041</TR>
2042<TR><TD ALIGN="LEFT">DOLLOP</TD>
2043<TD ALIGN="RIGHT">0.134</TD>
2044<TD ALIGN="RIGHT">0.141</TD>
2045<TD ALIGN="RIGHT">0.233</TD>
2046</TR>
2047<TR><TD ALIGN="LEFT">DOLPENNY</TD>
2048<TD ALIGN="RIGHT">0.051</TD>
2049<TD ALIGN="RIGHT">0.241</TD>
2050<TD ALIGN="RIGHT">101.29</TD>
2051</TR>
2052<TR><TD ALIGN="LEFT">CLIQUE</TD>
2053<TD ALIGN="RIGHT">0.010</TD>
2054<TD ALIGN="RIGHT">0.015</TD>
2055<TD ALIGN="RIGHT">0.020</TD>
2056</TR>
2057</TABLE>
2058</DIV>
2059
2060<P>
2061<BR>
2062
2063<P>
2064In all cases the programs were run under the default options without compiler
2065switches, except as
2066specified here.   The
2067data sets used for the discrete characters programs have <TT>0</TT>'s and <TT>1</TT>'s
2068instead of <TT>A</TT>'s and <TT>C</TT>'s.  For CONTML the <TT>A</TT>'s and <TT>C</TT>'s
2069were made into <TT>0.0</TT>'s and <TT>1.0</TT>'s and considered as 40 2-allele loci.
2070For the distance programs 10  x  10 distance matrices were
2071computed from the three data sets.
2072For the restriction sites programs <TT>A</TT> and <TT>C</TT> were changed into
2073<TT>+</TT> and <TT>-</TT>.  It does not
2074make much sense to benchmark MOVE, DOLMOVE, or DNAMOVE, although when there
2075are many characters and many species the response time after each
2076alteration of the tree should be proportional to the product of the number of
2077species and the number of characters.  For DNAML and DNAMLK the frequencies
2078of the four bases were
2079set to be equal rather than determined empirically as is the default.  For
2080RESTML the number of enzymes was set to 1.
2081<P>
2082In most cases, the benchmark was made more accurate by analyzing 10 data
2083sets using the <TT>M</TT> (Multiple data sets) option and dividing the resulting
2084time by 10.  Times were determined as user times using the Linux <TT>time</TT>
2085command.  Several patterns will be apparent from this.  The algorithms (MIX,
2086DOLLOP, CONTML, FITCH, KITSCH, PROTPARS, DNAPARS, DNACOMP, and
2087DNAML, DNAMLK, RESTML) that use the above-described addition strategy have
2088run times that do not depend strongly on the messiness of the data.  The only
2089exception to this is that if a data set such as the Random data requires
2090extra rounds of global rearrangements it takes longer.  The
2091programs differ greatly in run time: the likelihood programs RESTML, DNAML and
2092CONTML are quite a bit slower than the others.  The protein sequence parsimony
2093program, which has to do a considerable amount of bookkeeping to keep track of
2094which amino acids can mutate to each other, is also relatively slow.
2095<P>
2096Another class of algorithms includes PENNY, DOLPENNY, DNAPENNY and CLIQUE.
2097These are branch-and-bound methods: in principle they should have execution
2098times that rise exponentially with the number of species and/or
2099characters, and they might be much more sensitive to messy data.  This is
2100apparent with PENNY, DOLPENNY, and DNAPENNY, which go from being reasonably
2101fast with clean data to very slow with messy data.  DOLPENNY is particularly
2102slow on messy data - this is because this algorithm cannot make use of some of
2103the lower-bound calculations that are possible with DNAPENNY and PENNY.  CLIQUE
2104is very fast on all
2105data sets.  Although in theory it should bog down if the number of cliques in
2106the data is very large, that does not happen with random data, which in
2107fact has few cliques and those small ones.  Apparently the "worst-case"
2108data sets that cause exponential run time are much rarer for CLIQUE than for
2109the other branch-and-bound methods.
2110<P>
2111NEIGHBOR is quite fast compared to FITCH and KITSCH, and should make it
2112possible to run much larger cases, although the results are expected to be
2113a bit rougher than with those programs.
2114<BR>
2115<P>
2116<H3>Speed with different numbers of species</H3>
2117<P>
2118How will the speed depend on the number of species and the number
2119of characters?  For the sequential-addition algorithms, the speed should
2120be proportional to somewhere between the cube of the number of species and
2121the square of the number of species, and to the number
2122of characters.  Thus a case that has, instead of 10 species and 20
2123characters, 20 species and 50 characters would take (in the cubic case)
21242  x  2  x  2  x  2.5 = 20
2125times as long.  This implies that cases with more than 20 species will
2126be slow, and cases with more than 40 species <I>very</I> slow.  This places a
2127premium on working on small subproblems rather than just dumping a whole
2128large data set into the programs.
2129<P>
2130An exception to these rules will be some of the DNA programs that use an
2131aliasing device to save execution time.  In these programs execution time
2132will not necessarily increase proportional to the number of sites,
2133as sites that show the same pattern of nucleotides will be detected
2134as identical and the calculations for them will be done only once, which does
2135not lead to more execution time.  This is particularly
2136likely to happen with few species and many sites, or with data sets that have
2137small amounts of evolutionary divergence.
2138<P>
2139For programs FITCH and KITSCH, the distance matrix is square, so
2140that when we double the number of species we also double the number of
2141"characters", so that running times will go up as the fourth power of
2142the number of species rather than the third power.  Thus a 20-species
2143case with FITCH is expected to run sixteen times more slowly than a 10-species
2144case.
2145<P>
2146For programs like PENNY and CLIQUE the run times will rise faster
2147than the cube of the number of species (in fact, they can rise faster
2148than any power since these algorithms are not guaranteed to work in
2149polynomial time).  In practice, PENNY will frequently bog down above 11
2150species, while CLIQUE easily deals with larger numbers.
2151<P>
2152For NEIGHBOR the speed should vary only as the square of the number of
2153species, so a case twice as large will take only four times as long.  This
2154will make it an attractive alternative to FITCH and KITSCH for large data
2155sets.
2156<P>
2157<B>Note:</B> If you are unsure of how long a program will take, try it first on
2158a few species, then work your way up until you get a feel for the speed
2159and for what size programs you can afford to run.
2160<P>
2161Execution time is not the most important criterion for a program,
2162particularly as computer time gets much cheaper than your time or a
2163programmer's time.  With workstations on which background jobs can be run
2164all night, execution speed is not overwhelmingly relevant.  Some of us have been
2165conditioned by an earlier era of computing to consider execution speed
2166paramount.  But ease of use, ease of adaptation to your computer system,
2167and ease of modification are much more important in practice, and in
2168these respects I think these programs are adequate.  Only if you are
2169engaged in 1960's style mainframe computing, or if you have very large
2170amounts of data is minimization of execution
2171time paramount.
2172<P>
2173Nevertheless it would have been nice to have made the programs
2174faster.  The present speeds are a compromise between speed and
2175effectiveness: by making them slower and trying more rearrangements in the
2176trees, or by enumerating all possible trees, I could have made the programs
2177more likely to find the best tree.  By trying fewer rearrangements I
2178could have speeded them up, but at the cost of finding worse trees.  I
2179could also have speeded them up by writing critical sections in assembly
2180language, but this would have sacrificed ease of distribution to new
2181computer systems.  There are also some options included in these programs that
2182make it
2183harder to adopt some of the economies of bookkeeping that make other programs
2184faster.  However to some extent I have simply made the decision not to spend
2185time trying to speed up program bookkeeping when there were new likelihood and
2186statistical methods to be developed.
2187<BR>
2188<P>
2189<H3>Relative speed of different machines</H3>
2190<P>
2191It is interesting to compare different machines using DNAPARS as the
2192standard task.  One can rate a machine on the DNAPARS benchmark by summing the
2193times for all three of the data sets.  Here are relative total timings over
2194all three data sets (done with various versions of DNAPARS) for some machines,
2195taking a Pentium MMX 266 notebook computer running Linux with gcc as the
2196standard.  Benchmarks from versions 3.4 and 3.5 of the program are
2197included (respectively the Pascal and C versions whose timings are in
2198parentheses.  They are compared only with each other and are scaled to the
2199rest of the timings using the joint runs on the 386SX and the Pentium MMX 266.
2200This use of separate standards is necessary not
2201because of different languages but because different versions of the package
2202are being compared.  Thus, the "Time" is the ratio of the Total to that for
2203the Pentium, adjusted by the scalings of machines using 3.4 and 3.5 when
2204appropriate.  The Relative Speed is the reciprocal of the Time.
2205<P>
2206<DIV ALIGN="CENTER">
2207<TABLE CELLPADDING=3 BORDER="1">
2208<TR><TD ALIGN="LEFT"><B>Machine</B></TD>
2209<TD ALIGN="LEFT"><B>Operating<BR>System</B></TD>
2210<TD ALIGN="LEFT"><B>Compiler</B></TD>
2211<TD ALIGN="LEFT"><B>Total</B></TD>
2212<TD ALIGN="LEFT"><B>Time</B></TD>
2213<TD ALIGN="LEFT"><B>Relative<BR>Speed</B></TD>
2214</TR>
2215<TR><TD ALIGN="LEFT">Toshiba T1100+</TD>
2216<TD ALIGN="LEFT">MSDOS</TD>
2217<TD ALIGN="LEFT">Turbo Pascal 3.01A</TD>
2218<TD ALIGN="LEFT">(269)</TD>
2219<TD ALIGN="LEFT">1758.2</TD>
2220<TD ALIGN="LEFT">0.0005688</TD>
2221</TR>
2222<TR><TD ALIGN="LEFT">Apple Mac Plus</TD>
2223<TD ALIGN="LEFT">MacOS</TD>
2224<TD ALIGN="LEFT">Lightspeed Pascal 2</TD>
2225<TD ALIGN="LEFT">(175.84)</TD>
2226<TD ALIGN="LEFT">1149.3</TD>
2227<TD ALIGN="LEFT">0.0008701</TD>
2228</TR>
2229<TR><TD ALIGN="LEFT">Toshiba T1100+</TD>
2230<TD ALIGN="LEFT">MSDOS</TD>
2231<TD ALIGN="LEFT">Turbo Pascal 5.0</TD>
2232<TD ALIGN="LEFT">(162)</TD>
2233<TD ALIGN="LEFT">1058.9</TD>
2234<TD ALIGN="LEFT">0.0009443</TD>
2235</TR>
2236<TR><TD ALIGN="LEFT">Macintosh Classic</TD>
2237<TD ALIGN="LEFT">MacOS</TD>
2238<TD ALIGN="LEFT">Think Pascal 3</TD>
2239<TD ALIGN="LEFT">(160)</TD>
2240<TD ALIGN="LEFT">1045.8</TD>
2241<TD ALIGN="LEFT">0.0009562</TD>
2242</TR>
2243<TR><TD ALIGN="LEFT">Macintosh Classic</TD>
2244<TD ALIGN="LEFT">MacOS</TD>
2245<TD ALIGN="LEFT">Think C</TD>
2246<TD ALIGN="LEFT">(43.0)</TD>
2247<TD ALIGN="LEFT">795.6</TD>
2248<TD ALIGN="LEFT">0.0012569</TD>
2249</TR>
2250<TR><TD ALIGN="LEFT">IBM PS2/60</TD>
2251<TD ALIGN="LEFT">MSDOS</TD>
2252<TD ALIGN="LEFT">Turbo Pascal 5.0</TD>
2253<TD ALIGN="LEFT">(58.76)</TD>
2254<TD ALIGN="LEFT">384.00</TD>
2255<TD ALIGN="LEFT">0.002604</TD>
2256</TR>
2257<TR><TD ALIGN="LEFT">80286 (12 Mhz)</TD>
2258<TD ALIGN="LEFT">MSDOS</TD>
2259<TD ALIGN="LEFT">Turbo Pascal 5.0</TD>
2260<TD ALIGN="LEFT">(47.09)</TD>
2261<TD ALIGN="LEFT">307.77</TD>
2262<TD ALIGN="LEFT">0.003249</TD>
2263</TR>
2264<TR><TD ALIGN="LEFT">Apple Mac IIcx</TD>
2265<TD ALIGN="LEFT">MacOS</TD>
2266<TD ALIGN="LEFT">Think Pascal 3</TD>
2267<TD ALIGN="LEFT">(42)</TD>
2268<TD ALIGN="LEFT">274.44</TD>
2269<TD ALIGN="LEFT">0.003644</TD>
2270</TR>
2271<TR><TD ALIGN="LEFT">Apple Mac SE/30</TD>
2272<TD ALIGN="LEFT">MacOS</TD>
2273<TD ALIGN="LEFT">Think Pascal 3</TD>
2274<TD ALIGN="LEFT">(42)</TD>
2275<TD ALIGN="LEFT">274.44</TD>
2276<TD ALIGN="LEFT">0.003644</TD>
2277</TR>
2278<TR><TD ALIGN="LEFT">Apple Mac IIcx</TD>
2279<TD ALIGN="LEFT">MacOS</TD>
2280<TD ALIGN="LEFT">Lightspeed Pascal 2</TD>
2281<TD ALIGN="LEFT">(39.84)</TD>
2282<TD ALIGN="LEFT">260.44</TD>
2283<TD ALIGN="LEFT">0.003840</TD>
2284</TR>
2285<TR><TD ALIGN="LEFT">Apple Mac IIcx</TD>
2286<TD ALIGN="LEFT">MacOS</TD>
2287<TD ALIGN="LEFT">Lightspeed Pascal 2#</TD>
2288<TD ALIGN="LEFT">(39.69)</TD>
2289<TD ALIGN="LEFT">259.33</TD>
2290<TD ALIGN="LEFT">0.003856</TD>
2291</TR>
2292<TR><TD ALIGN="LEFT">Zenith Z386 (16MHz)</TD>
2293<TD ALIGN="LEFT">MSDOS</TD>
2294<TD ALIGN="LEFT">Turbo Pascal 5.0</TD>
2295<TD ALIGN="LEFT">(38.27)</TD>
2296<TD ALIGN="LEFT">256.67</TD>
2297<TD ALIGN="LEFT">0.003896</TD>
2298</TR>
2299<TR><TD ALIGN="LEFT">Macintosh SE/30</TD>
2300<TD ALIGN="LEFT">MacOS</TD>
2301<TD ALIGN="LEFT">Think C</TD>
2302<TD ALIGN="LEFT">(13.6)</TD>
2303<TD ALIGN="LEFT">251.56</TD>
2304<TD ALIGN="LEFT">0.003975</TD>
2305</TR>
2306<TR><TD ALIGN="LEFT">386SX (16 MHz)</TD>
2307<TD ALIGN="LEFT">MSDOS</TD>
2308<TD ALIGN="LEFT">Turbo Pascal 6.0</TD>
2309<TD ALIGN="LEFT">(34)</TD>
2310<TD ALIGN="LEFT">222.41</TD>
2311<TD ALIGN="LEFT">0.004496</TD>
2312</TR>
2313<TR><TD ALIGN="LEFT">386SX (16 MHz)</TD>
2314<TD ALIGN="LEFT">MSDOS</TD>
2315<TD ALIGN="LEFT">Microsoft Quick C</TD>
2316<TD ALIGN="LEFT">(12.01)</TD>
2317<TD ALIGN="LEFT">222.41</TD>
2318<TD ALIGN="LEFT">0.004496</TD>
2319</TR>
2320<TR><TD ALIGN="LEFT">Sequent-S81</TD>
2321<TD ALIGN="LEFT">DYNIX</TD>
2322<TD ALIGN="LEFT">Silicon Valley Pascal</TD>
2323<TD ALIGN="LEFT">(13.0)</TD>
2324<TD ALIGN="LEFT">84.89</TD>
2325<TD ALIGN="LEFT">0.011780</TD>
2326</TR>
2327<TR><TD ALIGN="LEFT">VAX 11/785</TD>
2328<TD ALIGN="LEFT">Unix</TD>
2329<TD ALIGN="LEFT">Berkeley Pascal</TD>
2330<TD ALIGN="LEFT">(11.9)</TD>
2331<TD ALIGN="LEFT">77.77</TD>
2332<TD ALIGN="LEFT">0.012857</TD>
2333</TR>
2334<TR><TD ALIGN="LEFT">80486-33</TD>
2335<TD ALIGN="LEFT">MSDOS</TD>
2336<TD ALIGN="LEFT">Turbo Pascal 6.0</TD>
2337<TD ALIGN="LEFT">(11.46)</TD>
2338<TD ALIGN="LEFT">74.89</TD>
2339<TD ALIGN="LEFT">0.013353</TD>
2340</TR>
2341<TR><TD ALIGN="LEFT">Sun 3/60</TD>
2342<TD ALIGN="LEFT">SunOS</TD>
2343<TD ALIGN="LEFT">Sun C</TD>
2344<TD ALIGN="LEFT">(3.93)</TD>
2345<TD ALIGN="LEFT">72.67</TD>
2346<TD ALIGN="LEFT">0.013761</TD>
2347</TR>
2348<TR><TD ALIGN="LEFT">NeXT Cube (68030)</TD>
2349<TD ALIGN="LEFT">Mach</TD>
2350<TD ALIGN="LEFT">Gnu C</TD>
2351<TD ALIGN="LEFT">(2.608)</TD>
2352<TD ALIGN="LEFT">48.256</TD>
2353<TD ALIGN="LEFT">0.02072</TD>
2354</TR>
2355<TR><TD ALIGN="LEFT">Sequent S-81</TD>
2356<TD ALIGN="LEFT">DYNIX</TD>
2357<TD ALIGN="LEFT">Sequent Symmetry C</TD>
2358<TD ALIGN="LEFT">(2.604)</TD>
2359<TD ALIGN="LEFT">48.182</TD>
2360<TD ALIGN="LEFT">0.02075</TD>
2361</TR>
2362<TR><TD ALIGN="LEFT">VAXstation 3500</TD>
2363<TD ALIGN="LEFT">Unix</TD>
2364<TD ALIGN="LEFT">Berkeley Pascal</TD>
2365<TD ALIGN="LEFT">(7.3)</TD>
2366<TD ALIGN="LEFT">47.777</TD>
2367<TD ALIGN="LEFT">0.02093</TD>
2368</TR>
2369<TR><TD ALIGN="LEFT">Sequent S-81</TD>
2370<TD ALIGN="LEFT">DYNIX</TD>
2371<TD ALIGN="LEFT">Berkeley Pascal</TD>
2372<TD ALIGN="LEFT">(5.6)</TD>
2373<TD ALIGN="LEFT">36.600</TD>
2374<TD ALIGN="LEFT">0.02732</TD>
2375</TR>
2376<TR><TD ALIGN="LEFT">Unisys 7000/40</TD>
2377<TD ALIGN="LEFT">Unix</TD>
2378<TD ALIGN="LEFT">Berkeley Pascal</TD>
2379<TD ALIGN="LEFT">(5.24)</TD>
2380<TD ALIGN="LEFT">34.244</TD>
2381<TD ALIGN="LEFT">0.02920</TD>
2382</TR>
2383<TR><TD ALIGN="LEFT">VAX 8600</TD>
2384<TD ALIGN="LEFT">VMS</TD>
2385<TD ALIGN="LEFT">DEC VAX Pascal</TD>
2386<TD ALIGN="LEFT">(3.96)</TD>
2387<TD ALIGN="LEFT">25.889</TD>
2388<TD ALIGN="LEFT">0.03863</TD>
2389</TR>
2390<TR><TD ALIGN="LEFT">Sun SPARC IPX</TD>
2391<TD ALIGN="LEFT">SunOS</TD>
2392<TD ALIGN="LEFT">Gnu C version 2.1</TD>
2393<TD ALIGN="LEFT">(1.28)</TD>
2394<TD ALIGN="LEFT">23.689</TD>
2395<TD ALIGN="LEFT">0.04221</TD>
2396</TR>
2397<TR><TD ALIGN="LEFT">VAX 6000-530</TD>
2398<TD ALIGN="LEFT">VMS</TD>
2399<TD ALIGN="LEFT">DEC C</TD>
2400<TD ALIGN="LEFT">(0.858)</TD>
2401<TD ALIGN="LEFT">15.867</TD>
2402<TD ALIGN="LEFT">0.06303</TD>
2403</TR>
2404<TR><TD ALIGN="LEFT">VAXstation 4000</TD>
2405<TD ALIGN="LEFT">VMS</TD>
2406<TD ALIGN="LEFT">DEC C</TD>
2407<TD ALIGN="LEFT">(0.809)</TD>
2408<TD ALIGN="LEFT">14.978</TD>
2409<TD ALIGN="LEFT">0.06677</TD>
2410</TR>
2411<TR><TD ALIGN="LEFT">IBM RS/6000 540</TD>
2412<TD ALIGN="LEFT">AIX</TD>
2413<TD ALIGN="LEFT">XLP Pascal</TD>
2414<TD ALIGN="LEFT">(2.276)</TD>
2415<TD ALIGN="LEFT">14.866</TD>
2416<TD ALIGN="LEFT">0.06726</TD>
2417</TR>
2418<TR><TD ALIGN="LEFT">NeXTstation(040/25)</TD>
2419<TD ALIGN="LEFT">Mach</TD>
2420<TD ALIGN="LEFT">Gnu C</TD>
2421<TD ALIGN="LEFT">(0.75)</TD>
2422<TD ALIGN="LEFT">13.867</TD>
2423<TD ALIGN="LEFT">0.07212</TD>
2424</TR>
2425<TR><TD ALIGN="LEFT">Sun SPARC IPX</TD>
2426<TD ALIGN="LEFT">SunOS</TD>
2427<TD ALIGN="LEFT">Sun C</TD>
2428<TD ALIGN="LEFT">(0.68)</TD>
2429<TD ALIGN="LEFT">12.580</TD>
2430<TD ALIGN="LEFT">0.07951</TD>
2431</TR>
2432<TR><TD ALIGN="LEFT">486DX (33 MHz)</TD>
2433<TD ALIGN="LEFT">Linux</TD>
2434<TD ALIGN="LEFT">Gnu C #</TD>
2435<TD ALIGN="LEFT">(0.63)</TD>
2436<TD ALIGN="LEFT">11.666</TD>
2437<TD ALIGN="LEFT">0.08571</TD>
2438</TR>
2439<TR><TD ALIGN="LEFT">Sun SPARCstation-1</TD>
2440<TD ALIGN="LEFT">Unix</TD>
2441<TD ALIGN="LEFT">Sun Pascal</TD>
2442<TD ALIGN="LEFT">(1.7)</TD>
2443<TD ALIGN="LEFT">11.111</TD>
2444<TD ALIGN="LEFT">0.09000</TD>
2445</TR>
2446<TR><TD ALIGN="LEFT">DECstation 5000/200</TD>
2447<TD ALIGN="LEFT">Unix</TD>
2448<TD ALIGN="LEFT">DEC Ultrix C</TD>
2449<TD ALIGN="LEFT">(0.45)</TD>
2450<TD ALIGN="LEFT">8.333</TD>
2451<TD ALIGN="LEFT">0.12000</TD>
2452</TR>
2453<TR><TD ALIGN="LEFT">Sun SPARC 1+</TD>
2454<TD ALIGN="LEFT">SunOS</TD>
2455<TD ALIGN="LEFT">Sun C</TD>
2456<TD ALIGN="LEFT">(0.40)</TD>
2457<TD ALIGN="LEFT">7.400</TD>
2458<TD ALIGN="LEFT">0.13513</TD>
2459</TR>
2460<TR><TD ALIGN="LEFT">DECstation 3100</TD>
2461<TD ALIGN="LEFT">Unix</TD>
2462<TD ALIGN="LEFT">DEC Ultrix Pascal</TD>
2463<TD ALIGN="LEFT">(0.77)</TD>
2464<TD ALIGN="LEFT">5.022</TD>
2465<TD ALIGN="LEFT">0.1991</TD>
2466</TR>
2467<TR><TD ALIGN="LEFT">IBM 3090-300E</TD>
2468<TD ALIGN="LEFT">AIX</TD>
2469<TD ALIGN="LEFT">Metaware High C</TD>
2470<TD ALIGN="LEFT">(0.27)</TD>
2471<TD ALIGN="LEFT">5.000</TD>
2472<TD ALIGN="LEFT">0.2000</TD>
2473</TR>
2474<TR><TD ALIGN="LEFT">DECstation 5000/125</TD>
2475<TD ALIGN="LEFT">Unix</TD>
2476<TD ALIGN="LEFT">DEC Ultrix C</TD>
2477<TD ALIGN="LEFT">(0.267)</TD>
2478<TD ALIGN="LEFT">4.933</TD>
2479<TD ALIGN="LEFT">0.2027</TD>
2480</TR>
2481<TR><TD ALIGN="LEFT">DECstation 5000/200</TD>
2482<TD ALIGN="LEFT">Unix</TD>
2483<TD ALIGN="LEFT">DEC Ultrix C</TD>
2484<TD ALIGN="LEFT">(0.256)</TD>
2485<TD ALIGN="LEFT">4.733</TD>
2486<TD ALIGN="LEFT">0.2113</TD>
2487</TR>
2488<TR><TD ALIGN="LEFT">Sun SPARC 4/50</TD>
2489<TD ALIGN="LEFT">SunOS</TD>
2490<TD ALIGN="LEFT">Sun C</TD>
2491<TD ALIGN="LEFT">(0.249)</TD>
2492<TD ALIGN="LEFT">4.607</TD>
2493<TD ALIGN="LEFT">0.2171</TD>
2494</TR>
2495<TR><TD ALIGN="LEFT">DEC 3000/400 AXP</TD>
2496<TD ALIGN="LEFT">Unix</TD>
2497<TD ALIGN="LEFT">DEC C</TD>
2498<TD ALIGN="LEFT">(0.224)</TD>
2499<TD ALIGN="LEFT">4.144</TD>
2500<TD ALIGN="LEFT">0.2413</TD>
2501</TR>
2502<TR><TD ALIGN="LEFT">DECstation 5000/240</TD>
2503<TD ALIGN="LEFT">Unix</TD>
2504<TD ALIGN="LEFT">DEC Ultrix C</TD>
2505<TD ALIGN="LEFT">(0.1889)</TD>
2506<TD ALIGN="LEFT">3.496</TD>
2507<TD ALIGN="LEFT">0.2861</TD>
2508</TR>
2509<TR><TD ALIGN="LEFT">SGI Iris R4000</TD>
2510<TD ALIGN="LEFT">Unix</TD>
2511<TD ALIGN="LEFT">SGI C</TD>
2512<TD ALIGN="LEFT">(0.184)</TD>
2513<TD ALIGN="LEFT">3.404</TD>
2514<TD ALIGN="LEFT">0.2937</TD>
2515</TR>
2516<TR><TD ALIGN="LEFT">IBM 3090-300E</TD>
2517<TD ALIGN="LEFT">VM</TD>
2518<TD ALIGN="LEFT">Pascal VS</TD>
2519<TD ALIGN="LEFT">(0.464)</TD>
2520<TD ALIGN="LEFT">3.022</TD>
2521<TD ALIGN="LEFT">0.3309</TD>
2522</TR>
2523<TR><TD ALIGN="LEFT">DECstation 5000/200</TD>
2524<TD ALIGN="LEFT">Unix</TD>
2525<TD ALIGN="LEFT">DEC Ultrix Pascal</TD>
2526<TD ALIGN="LEFT">(0.39)</TD>
2527<TD ALIGN="LEFT">2.533</TD>
2528<TD ALIGN="LEFT">0.3947</TD>
2529</TR>
2530<TR><TD ALIGN="LEFT">Pentium 120</TD>
2531<TD ALIGN="LEFT">Linux</TD>
2532<TD ALIGN="LEFT">Gnu C</TD>
2533<TD ALIGN="LEFT">1.848</TD>
2534<TD ALIGN="LEFT">1.994</TD>
2535<TD ALIGN="LEFT">0.5016</TD>
2536</TR>
2537<TR><TD ALIGN="LEFT">Pentium Pro 180</TD>
2538<TD ALIGN="LEFT">Linux</TD>
2539<TD ALIGN="LEFT">Gnu C</TD>
2540<TD ALIGN="LEFT">1.009</TD>
2541<TD ALIGN="LEFT">1.088</TD>
2542<TD ALIGN="LEFT">0.9353</TD>
2543</TR>
2544<TR><TD ALIGN="LEFT">Pentium 266 MMX</TD>
2545<TD ALIGN="LEFT">Linux</TD>
2546<TD ALIGN="LEFT">Gnu C (PHYLIP 3.5)</TD>
2547<TD ALIGN="LEFT">(0.054)</TD>
2548<TD ALIGN="LEFT">1.0</TD>
2549<TD ALIGN="LEFT">1.0</TD>
2550</TR>
2551<TR><TD ALIGN="LEFT">Pentium 266 MMX</TD>
2552<TD ALIGN="LEFT">Linux</TD>
2553<TD ALIGN="LEFT">Gnu C</TD>
2554<TD ALIGN="LEFT">0.927</TD>
2555<TD ALIGN="LEFT">1.0</TD>
2556<TD ALIGN="LEFT">1.0</TD>
2557</TR>
2558<TR><TD ALIGN="LEFT">Pentium 200</TD>
2559<TD ALIGN="LEFT">Linux</TD>
2560<TD ALIGN="LEFT">Gnu C</TD>
2561<TD ALIGN="LEFT">0.853</TD>
2562<TD ALIGN="LEFT">0.9202</TD>
2563<TD ALIGN="LEFT">1.2647</TD>
2564</TR>
2565<TR><TD ALIGN="LEFT">SGI PowerChallenge</TD>
2566<TD ALIGN="LEFT">Irix</TD>
2567<TD ALIGN="LEFT">Gnu C</TD>
2568<TD ALIGN="LEFT">0.844</TD>
2569<TD ALIGN="LEFT">0.9297</TD>
2570<TD ALIGN="LEFT">1.0756</TD>
2571</TR>
2572<TR><TD ALIGN="LEFT">DEC Alpha 400 4/233</TD>
2573<TD ALIGN="LEFT">DUNIX</TD>
2574<TD ALIGN="LEFT">Digital C (cc -fast)</TD>
2575<TD ALIGN="LEFT">0.730</TD>
2576<TD ALIGN="LEFT">0.7875</TD>
2577<TD ALIGN="LEFT">1.2699</TD>
2578</TR>
2579<TR><TD ALIGN="LEFT">Pentium II 500</TD>
2580<TD ALIGN="LEFT">Linux</TD>
2581<TD ALIGN="LEFT">Gnu C</TD>
2582<TD ALIGN="LEFT">0.368</TD>
2583<TD ALIGN="LEFT">0.4053</TD>
2584<TD ALIGN="LEFT">2.467</TD>
2585</TR>
2586<TR><TD ALIGN="LEFT">Compaq/Digital Alpha 500au</TD>
2587<TD ALIGN="LEFT">DUNIX</TD>
2588<TD ALIGN="LEFT">Digital C (cc -fast)</TD>
2589<TD ALIGN="LEFT">0.167</TD>
2590<TD ALIGN="LEFT">0.1805</TD>
2591<TD ALIGN="LEFT">5.541</TD>
2592</TR>
2593</TABLE>
2594</DIV>
2595<P>
2596This benchmark not only reflects integer performance of these machines
2597(as DNAPARS has few floating-point operations) but also the efficiency
2598of the compilers.  Some of the machines (the DEC 3000/400 AXP
2599and the IBM RS/6000, in particular) are much faster than this benchmark
2600would indicate.  The numerical programs benchmark below gives them a
2601fairer test.  The Compaq/Digital Alpha 500au times are exaggerated because,
2602although their compiles are optimized for that processor, the Pentium
2603compiles are not similarly optimized.
2604<P>
2605Note that parallel machines like the Sequent and the SGI PowerChallenge are not
2606really as slow as indicated by the data here, as these runs did nothing to take
2607advantage of their parallelism.
2608<P>
2609These benchmarks have now extended over 13 years, and in the DNAPARS
2610benchmark they extend over a range of 8000-fold in speed!
2611The experience of our laboratory, which seems typical, is that
2612computer power grows by a factor of about 1.85 per year.  This is
2613roughly consistent with these benchmarks.
2614<P>
2615For a picture of speeds for a more numerically intensive program,
2616here are benchmarks using DNAML, with the Pentium MMX 266
2617as the standard.  Some of the timings, the ones in parentheses, are
2618using PHYLIP version 3.5, and those are compared to that version run on
2619the Pentium 266.  Runs using the PHYLIP 3.4 Pascal version are adjusted
2620using the 386SX timings where both were run.  Numbers are
2621total run times (total user time in the case of Unix) over all three data sets.
2622<P>
2623<DIV ALIGN="CENTER">
2624<TABLE CELLPADDING=3 BORDER="1">
2625<TR><TD ALIGN="LEFT"><B>Machine</B></TD>
2626<TD ALIGN="LEFT"><B>Operating<BR>System</B></TD>
2627<TD ALIGN="LEFT"><B>Compiler</B></TD>
2628<TD ALIGN="RIGHT"><B>Seconds</B></TD>
2629<TD ALIGN="LEFT"><B>Time</B></TD>
2630<TD ALIGN="RIGHT"><B>Relative<BR>Speed</B></TD>
2631</TR>
2632<TR><TD ALIGN="LEFT">386SX 16 Mhz</TD>
2633<TD ALIGN="LEFT">PCDOS</TD>
2634<TD ALIGN="LEFT">Turbo Pascal 6</TD>
2635<TD ALIGN="RIGHT">(7826)</TD>
2636<TD ALIGN="LEFT"> 181.18</TD>
2637<TD ALIGN="RIGHT">0.005519</TD>
2638</TR>
2639<TR><TD ALIGN="LEFT">386SX 16 Mhz</TD>
2640<TD ALIGN="LEFT">PCDOS</TD>
2641<TD ALIGN="LEFT">Quick C</TD>
2642<TD ALIGN="RIGHT">(6549.79)</TD>
2643<TD ALIGN="LEFT"> 181.18</TD>
2644<TD ALIGN="RIGHT">0.005519</TD>
2645</TR>
2646<TR><TD ALIGN="LEFT">Compudyne 486DX/33</TD>
2647<TD ALIGN="LEFT">Linux</TD>
2648<TD ALIGN="LEFT">Gnu C</TD>
2649<TD ALIGN="RIGHT">(1599.9)</TD>
2650<TD ALIGN="LEFT"> 44.26</TD>
2651<TD ALIGN="RIGHT">0.022595</TD>
2652</TR>
2653<TR><TD ALIGN="LEFT">SUN Sparcstation 1+</TD>
2654<TD ALIGN="LEFT">SunOS</TD>
2655<TD ALIGN="LEFT">Sun C</TD>
2656<TD ALIGN="RIGHT">(1402.8)</TD>
2657<TD ALIGN="LEFT"> 38.805</TD>
2658<TD ALIGN="RIGHT">0.025770</TD>
2659</TR>
2660<TR><TD ALIGN="LEFT">Everex STEP 386/20</TD>
2661<TD ALIGN="LEFT">PCDOS</TD>
2662<TD ALIGN="LEFT">Turbo Pascal 5.5</TD>
2663<TD ALIGN="RIGHT">(1440.8)</TD>
2664<TD ALIGN="LEFT"> 33.356</TD>
2665<TD ALIGN="RIGHT"> 0.029980</TD>
2666</TR>
2667<TR><TD ALIGN="LEFT">486DX/33</TD>
2668<TD ALIGN="LEFT">PCDOS</TD>
2669<TD ALIGN="LEFT">Turbo C++</TD>
2670<TD ALIGN="RIGHT">(1107.2)</TD>
2671<TD ALIGN="LEFT"> 30.628</TD>
2672<TD ALIGN="RIGHT">0.032650</TD>
2673</TR>
2674<TR><TD ALIGN="LEFT">Compudyne 486DX/33</TD>
2675<TD ALIGN="LEFT">PCDOS</TD>
2676<TD ALIGN="LEFT">Waterloo C/386</TD>
2677<TD ALIGN="RIGHT">(1045.78)</TD>
2678<TD ALIGN="LEFT"> 28.929</TD>
2679<TD ALIGN="RIGHT">0.034567</TD>
2680</TR>
2681<TR><TD ALIGN="LEFT">Sun SPARCstation IPX</TD>
2682<TD ALIGN="LEFT">SunOS</TD>
2683<TD ALIGN="LEFT">Gnu C</TD>
2684<TD ALIGN="RIGHT"> (960.2)</TD>
2685<TD ALIGN="LEFT"> 26.562</TD>
2686<TD ALIGN="RIGHT">0.037648</TD>
2687</TR>
2688<TR><TD ALIGN="LEFT">NeXTstation(68040/25)</TD>
2689<TD ALIGN="LEFT">Mach</TD>
2690<TD ALIGN="LEFT">Gnu C</TD>
2691<TD ALIGN="RIGHT"> (916.6)</TD>
2692<TD ALIGN="LEFT"> 25.355</TD>
2693<TD ALIGN="RIGHT">0.039439</TD>
2694</TR>
2695<TR><TD ALIGN="LEFT">486DX/33</TD>
2696<TD ALIGN="LEFT">PCDOS</TD>
2697<TD ALIGN="LEFT">Waterloo C/386</TD>
2698<TD ALIGN="RIGHT"> (861.0)</TD>
2699<TD ALIGN="LEFT"> 23.817</TD>
2700<TD ALIGN="RIGHT">0.041986</TD>
2701</TR>
2702<TR><TD ALIGN="LEFT">Sun SPARCstation IPX</TD>
2703<TD ALIGN="LEFT">SunOS</TD>
2704<TD ALIGN="LEFT">Sun C</TD>
2705<TD ALIGN="RIGHT"> (787.7)</TD>
2706<TD ALIGN="LEFT"> 21.790</TD>
2707<TD ALIGN="RIGHT">0.045893</TD>
2708</TR>
2709<TR><TD ALIGN="LEFT">486DX/33</TD>
2710<TD ALIGN="LEFT">PCDOS</TD>
2711<TD ALIGN="LEFT">Gnu C</TD>
2712<TD ALIGN="RIGHT"> (650.9)</TD>
2713<TD ALIGN="LEFT"> 18.006</TD>
2714<TD ALIGN="RIGHT">0.05554</TD>
2715</TR>
2716<TR><TD ALIGN="LEFT">VAX 6000-530</TD>
2717<TD ALIGN="LEFT">VMS</TD>
2718<TD ALIGN="LEFT">DEC C</TD>
2719<TD ALIGN="RIGHT"> (637.0)</TD>
2720<TD ALIGN="LEFT"> 17.621</TD>
2721<TD ALIGN="RIGHT">0.05675</TD>
2722</TR>
2723<TR><TD ALIGN="LEFT">DECstation 5000/200</TD>
2724<TD ALIGN="LEFT">Unix</TD>
2725<TD ALIGN="LEFT">DEC Ultrix RISC C</TD>
2726<TD ALIGN="RIGHT"> (423.3)</TD>
2727<TD ALIGN="LEFT"> 11.710</TD>
2728<TD ALIGN="RIGHT">0.08540</TD>
2729</TR>
2730<TR><TD ALIGN="LEFT">IBM 3090-300E</TD>
2731<TD ALIGN="LEFT">AIX</TD>
2732<TD ALIGN="LEFT">Metaware High C</TD>
2733<TD ALIGN="RIGHT"> (201.8)</TD>
2734<TD ALIGN="LEFT">  5.582</TD>
2735<TD ALIGN="RIGHT">0.17914</TD>
2736</TR>
2737<TR><TD ALIGN="LEFT">Convex C240/1024</TD>
2738<TD ALIGN="LEFT">Unix</TD>
2739<TD ALIGN="LEFT">C</TD>
2740<TD ALIGN="RIGHT"> (101.6)</TD>
2741<TD ALIGN="LEFT">  2.8105</TD>
2742<TD ALIGN="RIGHT">0.35581</TD>
2743</TR>
2744<TR><TD ALIGN="LEFT">DEC 3000/400 AXP</TD>
2745<TD ALIGN="LEFT">Unix</TD>
2746<TD ALIGN="LEFT">DEC C</TD>
2747<TD ALIGN="RIGHT">  (98.29)</TD>
2748<TD ALIGN="LEFT">  2.7189</TD>
2749<TD ALIGN="RIGHT">0.36779</TD>
2750</TR>
2751<TR><TD ALIGN="LEFT">Pentium 120</TD>
2752<TD ALIGN="LEFT">Linux</TD>
2753<TD ALIGN="LEFT">Gnu C</TD>
2754<TD ALIGN="RIGHT">25.26</TD>
2755<TD ALIGN="LEFT">3.3906</TD>
2756<TD ALIGN="RIGHT">0.29493</TD>
2757</TR>
2758<TR><TD ALIGN="LEFT">Pentium Pro 180</TD>
2759<TD ALIGN="LEFT">Linux</TD>
2760<TD ALIGN="LEFT">Gnu C</TD>
2761<TD ALIGN="RIGHT">18.88</TD>
2762<TD ALIGN="LEFT">2.5342</TD>
2763<TD ALIGN="RIGHT">0.3946</TD>
2764</TR>
2765<TR><TD ALIGN="LEFT">Pentium 200</TD>
2766<TD ALIGN="LEFT">Linux</TD>
2767<TD ALIGN="LEFT">Gnu C</TD>
2768<TD ALIGN="RIGHT">16.51</TD>
2769<TD ALIGN="LEFT">2.2161</TD>
2770<TD ALIGN="RIGHT">0.4512</TD>
2771</TR>
2772<TR><TD ALIGN="LEFT">SGI PowerChallenge</TD>
2773<TD ALIGN="LEFT">IRIX</TD>
2774<TD ALIGN="LEFT">Gnu C</TD>
2775<TD ALIGN="RIGHT">12.446</TD>
2776<TD ALIGN="LEFT">1.6706</TD>
2777<TD ALIGN="RIGHT">0.5985</TD>
2778</TR>
2779<TR><TD ALIGN="LEFT">Pentium MMX 266</TD>
2780<TD ALIGN="LEFT">Linux</TD>
2781<TD ALIGN="LEFT">Gnu C (PHYLIP 3.5)</TD>
2782<TD ALIGN="RIGHT">(36.15)</TD>
2783<TD ALIGN="LEFT"> 1.0</TD>
2784<TD ALIGN="RIGHT"> 1.0</TD>
2785</TR>
2786<TR><TD ALIGN="LEFT">DEC Alpha 400 4/233</TD>
2787<TD ALIGN="LEFT">Linux</TD>
2788<TD ALIGN="LEFT">Gnu C (cc -fast)</TD>
2789<TD ALIGN="RIGHT">8.0418</TD>
2790<TD ALIGN="LEFT">1.0792</TD>
2791<TD ALIGN="RIGHT">0.9266</TD>
2792</TR>
2793<TR><TD ALIGN="LEFT">Pentium MMX 266</TD>
2794<TD ALIGN="LEFT">Linux</TD>
2795<TD ALIGN="LEFT">Gnu C</TD>
2796<TD ALIGN="RIGHT">7.45</TD>
2797<TD ALIGN="LEFT"> 1.0</TD>
2798<TD ALIGN="RIGHT"> 1.0</TD>
2799</TR>
2800<TR><TD ALIGN="LEFT">Pentium II 500</TD>
2801<TD ALIGN="LEFT">Linux</TD>
2802<TD ALIGN="LEFT">Gnu C</TD>
2803<TD ALIGN="RIGHT">6.02</TD>
2804<TD ALIGN="LEFT"> 0.8081</TD>
2805<TD ALIGN="RIGHT"> 1.2375</TD>
2806</TR>
2807<TR><TD ALIGN="LEFT">Compaq/Digital Alpha 500au</TD>
2808<TD ALIGN="LEFT">Linux</TD>
2809<TD ALIGN="LEFT">Gnu C (cc -fast)</TD>
2810<TD ALIGN="RIGHT">0.9383</TD>
2811<TD ALIGN="LEFT"> 0.1259</TD>
2812<TD ALIGN="RIGHT">7.940</TD>
2813</TR>
2814</TABLE>
2815</DIV>
2816<P>
2817As before, the parallel machines such as the Convex and the SGI PowerChallenge
2818were only run using one processor, which does not take into account the
2819gain that could be obtained by parallelizing the programs.  The speed of the
2820Compaq/Digital Alpha 500au is exaggerated because it was compiled in a way
2821optimized for its processor, while the Pentium compiles were not.
2822<P>
2823You are invited to send me figures for your machine for
2824inclusion in future tables.  Use the data sets above and compute the total
2825times for DNAPARS and for DNAML for the three data sets (setting the
2826frequencies of the four bases to 0.25 each for the DNAML runs).  Be sure to
2827tell me the name and version of your compiler, and the version of PHYLIP you
2828tested.
2829If the times are too small to be measured accurately, obtain the times
2830for ten data sets (the Multiple data sets option) and divide by 10.
2831<P>
2832<A NAME="comments"><HR><P></A>
2833<DIV ALIGN="CENTER">
2834<H2>General Comments on Adapting<BR>
2835the Package to Different Computer Systems</H2></DIV>
2836<P>
2837In the sections following you will find instructions on how to adapt the
2838programs to different computers and compilers.  The programs should compile
2839without alteration on most versions of C.  They use the "malloc" library
2840or "calloc" function to allocate memory so that the upper limits on how many
2841species or how many sites or characters they can run is set by the system memory
2842available to that memory-allocation function.
2843<P>
2844In the document file for each program, I have supplied a small
2845input example, and the output it produces, to help you check whether the
2846programs are running properly.
2847<P>
2848<DIV ALIGN=CENTER>
2849<A NAME="compiling"><HR><P></A>
2850<H2>Compiling the programs</H2>
2851</DIV>
2852<P>
2853If you have not been able to get executables for PHYLIP, you should be
2854able to make your own.  This is easy under Unix and Linux, but more
2855difficult if you have a Macintosh or a Windows system.  If you have the
2856latter, we stringly recommend you download and use the PowerMac and
2857Windows executables that we distribute.  If you do that, you will not need
2858to have any compiler or to do any compiling.  I get a certain number of
2859inquiries each year from confused users who are not sure what a compiler
2860is but think they need one.  After downloading the executables they
2861contact me and complain that they did not find a compiler included in the
2862package, and would I please e-mail them the compiler.  What they really
2863need to do is use the executables and forget about compiling them.
2864<P>
2865Some users may also need to compile the programs in order to modify them.
2866The instructions below will help with this.
2867<P>
2868I will discuss how to compile PHYLIP using one of a number of widely-used
2869compilers.  After these I will comment on compiling PHYLIP on other, less
2870widely-used systems.
2871<P>
2872<H3>Unix and Linux</H3>
2873<P>
2874In Unix and Linux (which is Unix in all important functional respects, if
2875not in all
2876legal respects) it is easy to compile PHYLIP yourself, which is why we have
2877generally not bothered to distribute executables for Unix.  Unix (and Linux)
2878systems generally have a C compiler and have the <TT>make</TT> utility.  We
2879distribute with the PHYLIP source code a Unix-compatible <TT>Makefile</TT>.
2880<P>
2881After you have finished unpacking the Documentation and Source Code
2882archive, you will find that you have created a directory <TT>phylip</TT>
2883in which there are three
2884subdirectories, called <TT>exe</TT>, <TT>src</TT>, and <TT>doc</TT>. 
2885There is also an HTML web page, <TT>phylip.html</TT>.  The <TT>exe</TT>
2886directory
2887will be empty, <TT>src</TT> contains the source code files, including the
2888<TT>Makefile</TT>.  Directory <TT>doc</TT> contains the documentation files.
2889<P>
2890Enter the <TT>src</TT> directory.  Before you compile, you will want to
2891look at the makefile and see whether you want to alter the compilation
2892command.  There are careful instructions in the Makefile telling you how to
2893do this.  To compile all the programs just type:
2894<P>
2895<TT>make install</TT>
2896<P>
2897You will then see the compiling commands as they happen, with
2898occasional warning messages.  If these are warnings, rather than errors,
2899they are not too serious.  A typical warning would be like this:
2900<P>
2901<TT>dnaml.c:1204: warning: static declaration for re_move follows non-static</TT>
2902<P>
2903After a time the compiler will finish compiling.  If you have done a
2904<TT>make install</TT> the system will then move the executables into the
2905<TT>exe</TT> subdirectory and also save space by erasing all the relocatable
2906object files that were produced in the process.  You should be left with
2907useable executables in the <TT>exe</TT> directory, and the <TT>src</TT>
2908directory should be as before.   To run the executables, go into the
2909<TT>exe</TT> directory and type the program name (say <TT>dnaml</TT>).
2910The names of the
2911executables will be the same as the names of the C programs, but without the
2912<TT>.c</TT> suffix.  Thus <TT>dnaml.c</TT> compiles to make an executable called <TT>dnaml</TT>.
2913<P>
2914A typical Unix or Linux installation would put the directory <TT>phylip</TT>
2915in <TT>/usr/local</TT>.  The name of the executables directory <TT>EXEDIR</TT>
2916could be changed to be <TT>/usr/local/bin</TT>, so that the <TT>make install</TT>
2917command puts the executables there.  If the users have <TT>/usr/local/bin</TT>
2918in their paths, the programs would be found when their names are typed.
2919The font files <TT>font1</TT> through <TT>font6</TT> could also be
2920placed there.  A batch script containing the lines
2921<P>
2922<PRE>
2923      ln -s /usr/local/bin/font1 font1
2924      ln -s /usr/local/bin/font2 font2
2925      ln -s /usr/local/bin/font3 font3
2926      ln -s /usr/local/bin/font4 font4
2927      ln -s /usr/local/bin/font5 font5
2928      ln -s /usr/local/bin/font6 font6
2929</PRE>
2930<P>
2931could be used to establish links in the user's working directory so that
2932Drawtree and Drawgram would find these font files when users
2933type a name such as <TT>font1</TT> when the program asks
2934them for a font file name.  The
2935documentation web pages are in subdirectory <TT>doc</TT> of the
2936main PHYLIP directory, except for one, <TT>phylip.html</TT> which is
2937in the main PHYLIP directory.  It has a table of all of the documentation
2938pages, including this one.  If users create a bookmark to that page
2939it can be used to access all of the other documentation pages.
2940<P>
2941To compile just one program, such as DNAML, type:
2942<P>
2943<TT>make dnaml</TT>
2944<P>
2945After this compilation, <TT>dnaml</TT> will be in the <TT>src</TT>
2946subdirectory.  So will some rrelocatable object code files that
2947were used to create the executable.  These have names ending in
2948<TT>.o</TT> - they can safely be deleted.
2949<P>
2950If you have problems with the compilation command, you can edit the
2951<TT>Makefile</TT>.  It has careful explanations at its front of how you
2952might want to do so.  For example, you might want to change the C
2953compiler name <TT>cc</TT> to the name of the Gnu C compiler, <TT>gcc</TT>.
2954This can be done by removing the comment character <TT>#</TT> from the
2955front of one line, and placing it at the front of a nearby line.
2956How to do so should be clear from the material at the beginning of the
2957<TT>Makefile</TT>.  We have included sample lines for using the <TT>gcc</TT>
2958compiler and for using the Cygwin Gnu C++ environment on Windows, as
2959well as the default of <TT>cc</TT>.
2960<P>
2961Some older C compilers (notably the Berkeley C compiler which is
2962included free with some Sun systems) do not adhere to the ANSI C
2963standard (because they were written before it was set down).
2964They have trouble with the function prototypes which are in
2965our programs.  We have included an <TT>#ifndef</TT> preprocessor
2966command to eliminate the problem, if you use the switch <TT>-DOLDC</TT>
2967when compiling.  Thus with these compilers you need only use this in
2968your C flags (in the Makefile) and compilers such as Berkeley C
2969will cause no trouble.
2970<P>
2971<H3>Macintosh PowerMacs</H3>
2972<P>
2973<B>Compiling with Metrowerks Codewarrior on Macintosh PowerMacs...</B>
2974<P>
2975We shall assume that you have a recent version of the Metrowerks
2976Codewarrior  C++
2977compiler.  This description, and the project files that we provide,
2978assume Codewarrior 5.3.  We also assume some familiarity with
2979the use of the Codewarrior compiler and its Integrated Development
2980Environment (IDE).
2981<P>
2982Start with our <TT>src</TT> directory (folder) that contains the C source
2983code files such as <TT>dnaml.c</TT> and also the Codewarrior resource
2984files such as <TT>dnaml.rsrc</TT>, which are provided by us.
2985<P>
2986<B>Creating the project file.</B>  We will use DnaML as our example.
2987We have provided a full set of project files in the
2988self-extracting Macintosh archive.
2989<EM>If you have them then you do not need
2990to do the items on the following list:</EM>
2991<OL>
2992<LI>Start up the Codewarrior IDE integrated development environment.
2993<LI>Create a new project file by choosing <TT>New...</TT> on the <TT>File</TT>
2994menu.
2995<LI>Type in the project name <TT>dnaml.proj</TT>
2996<LI>On the Project menu on the left side of the <TT>New</TT> window, double-click on <TT>MacOS C/C++ Stationery</TT>
2997<LI>In the <TT>New project</TT> window that opens, click on the triangle
2998to the left of <TT>Standard Console</TT>.
2999<LI>Move the slider at the right of the window down until you reach
3000<TT>SIOUX-WASTE</TT>
3001<LI>Click on the triangle to the left of <TT>SIOUX-WASTE</TT>.  This opens
3002another list of choices below.
3003<LI>Click on the menu item <TT>SIOUX-WASTE C PPC</TT>. Press the <TT>OK</TT> button.  After a bit a window <TT>dnaml.proj</TT> will open.
3004<LI>Click on the triangle to the left of the <TT>Sources</TT> menu item.  A
3005template item called <TT>HelloWorld.c</TT> will open.
3006<LI>Select <TT>HelloWorld.c</TT>.
3007<LI>Open the <TT>Edit</TT> menu at the top of the Mac screen and select
3008<TT>Clear</TT>.  A box will open asking if you want to remove <TT>HelloWorld.c</TT> from the project.
3009<LI>Select <TT>OK</TT>.
3010<LI>If the <TT>dnaml.c</TT> file came from the self-extracting Macintosh
3011archive that we distribute, it should show a yellow-and-back-striped Metrowerks
3012icon (if not, as when you get it from some other form of our distribution,
3013you may have to pass it through a program like Microsoft Word, making
3014sure to save it as a Text Only file, to get
3015Metrowerks to be able to see it as a potential source code file).
3016<LI>Drag the <TT>dnaml.c</TT> file onto the <TT>Sources</TT> item in your
3017<TT>dnaml.proj</TT> window.
3018<LI>Drop it onto Sources so that it appears under the <TT>Sources</TT> choice.
3019This may take a few tries -- if it appears above <TT>Sources</TT> grab it
3020and move it again.
3021<LI>Now add the other files that must be compiled with <TT>dnaml.c</TT>.
3022These can be identified by looking at our <TT>Makefile</TT> -- for DnaML
3023they are <TT>seq.c</TT>, <TT>phylip.c</TT>, <TT>seq.h</TT>, and <TT>phylip.h</TT>.  Each of them needs to be added to the project file in the same way that
3024<TT>dnaml.c</TT> was.
3025<LI>Drag <TT>dnaml.rsrc</TT> into <TT>Sources</TT> in the same way.  It
3026doesn't matter whether it appears before or after <TT>dnaml.c</TT>.
3027<LI>Go to the <TT>Edit</TT> menu and select the <TT>PPC Std C SIOUX-WASTE Settings</TT> item.  A window of that name will then open.
3028<LI>Under the <TT>Target</TT> item you will see a <TT>PPC Target</TT> item.
3029Select it.  A <TT>PPC Target</TT> window will open to the right.
3030<LI>Change the name in the <TT>File Name</TT> box to be <TT>PHYLIP</TT>
3031<LI>Change the <TT>????</TT> in the <TT>Creator</TT> box to (say) <TT>PHYD</TT>
3032<LI>Change the <TT>Preferred Heap Size</TT> to <TT>1024</TT>.
3033<! need to add selections of PPC Processor here >
3034<! ditto for Global Optimization >
3035<LI>Under <TT>Language Settings</TT> in the left-hand menu of the window,
3036select <TT>C/C++ Language</TT>.  A window called <TT>C/C++ Language</TT>
3037will open to the immediate right.
3038<LI>Click on <TT>Require Function Prototypes</TT> to deselect that setting.
3039<LI>Click on the <TT>Save</TT> button at the lower-right of the project
3040settings window.
3041<LI>Close the <TT>PPC Std C SIOUX-WASTE Settings</TT> window using the usual
3042box in the upper-left corner.
3043<LI>On your Desktop you should now find a folder <TT>PHYLIP</TT>.
3044If it has a
3045file called <TT>HelloWorld.c</TT> you may want to discard that file.
3046<LI>In that <TT>PHYLIP</TT> folder you will find a file <TT>dnaml.proj</TT>.
3047<LI>Double-click on that project file.  If the Metrowerks is not already open,
3048it should open now.
3049<LI>If a window called <TT>Project Messages</TT> opens and there is a
3050complaint in it about access paths being wrong, you should fix these by
3051selecting the <TT>Reset project entry paths</TT> item in the <TT>Project</TT>
3052menu.
3053<LI>Select the <TT>Make</TT> item in the <TT>Project</TT> menu.
3054<LI>In the <TT>Project</TT> menu, select <TT>Make</TT>
3055</OL>
3056<B>Compiling a program once its resource file is available.</B>.
3057If the resource files are all available (as they should be), you did not need
3058to do any of the above.   Usually users will have no need to compile
3059the programs, but occasionally they may want to change a setting or
3060add a feature.  In that case the Metrowerks Codewarrior compiler can be
3061used.  We have provided support for compiling the programs in its
3062most recent version, version 5.3.  The following discussion will
3063assume that you have obtained and installed the compiler.
3064<P>
3065You should find in the source code directory
3066<TT>src</TT> a subdirectory called <TT>mac</TT> which contains the
3067Metrowerks Codewarrior compiler "project files" (with names ending in
3068<TT>.proj</TT>, as well as the resource files (which end in <TT>.rsrc</TT>
3069for each program.  You can get into this subdirectory, activate the
3070Metrowerks compiler, and open the appropriate project file.  To
3071compile the program, simply make sure that the project file is an
3072active window, and type <TT>Command-M</TT> (which is to say, hold down
3073the <TT>Command</TT> key while typing <TT>M</TT>).  Alternatively,
3074pull down the <TT>Project</TT> window and select <TT>Make</TT>.  The
3075program should then compile, possibly with ignorable warning messages.
3076<P>
3077<H3>Windows systems</H3>
3078<P>
3079<B>Compiling with Microsoft Visual C++</B> 
3080<P>
3081Microsoft Visual C++ is used to compile the executables we distribute
3082Windows.  It can compile using a Makefile.  We have supplied this
3083in the source code distrubution as <TT>Makefile.msvc</TT>.
3084You will need to preserve the Unix Makefile by renaming it to, say,
3085<TT>Makefile.unix</TT>, then make a copy of <TT>Makefile.msvc</TT>
3086and call it <TT>Makefile</TT>.
3087<P>
3088<B>Setting the path.</B>
3089Before using <TT>nmake</TT> you will need to have the paths
3090set properly.  For this, use the Start menu to open Command or
3091a Dos Prompt first.  To set the path type<BR>
3092<PRE>
3093set MSVC=Path
3094</PRE>
3095where Path is where Microsoft Visual Studio is installed
3096(e.g. it might be in <TT>c:\Microsoft Visual Studio</TT>).
3097However the path you type should not have any spaces in it.
3098This means that you may have to use the directory's
3099DOS filename.  In general to get a DOS name you take the first six letters of
3100the directory name and follow them by <TT>~1</TT>. For example,
3101<TT>Microsoft Visual Studio</TT> will have a DOS name
3102<TT>Micros~1</TT>, <TT>Program Files</TT> will be <TT>Progra~1</TT>).
3103Depending on what other
3104file are in the directory the DOS name may be the first six letters followed
3105by <TT>~2,~3,~4</TT>, etc... (e.g. <TT>Micros~3</TT> or <TT>Progra~5</TT>).
3106It may take some
3107experimentation to figure it out. With older Versions of Windows (pre-win2000)
3108it may be possible to just right click on the directory icon and select
3109Properties to get the DOS name.
3110<P>
3111Once you have set MSVC, type
3112<PRE>
3113PATH=%PATH%;%MSVC%\VC98\bin
3114</PRE>
3115Then the Makefile will need to be edited.  The line
3116<PRE>
3117MSVCPATH=c:\Micros~1\VC98
3118</PRE>
3119will need to be changed so that
3120It points to whereever Microsoft Visual Studio is installed followed by
3121 <TT>\VC98</TT>.
3122<P>
3123<B>Using the Makefile</B>. The Makefile is invoked using the
3124<TT>nmake</TT> command.  If you simply type <TT>nmake</TT> you
3125will get a list of possible <TT>make</TT> commands.  For example,
3126to compile a single program such as <TT>Dnaml</TT> but not
3127install it, type <TT>make dnaml</TT>.  To compile and install all
3128programs type <TT>make install</TT>.  We have supplied all the
3129support files and icons needed for the compilations.  They are
3130in subdirectory <TT>msvc</TT> of the main source code
3131directory.
3132<P>
3133<B>Compiling with Borland C++</B> 
3134<P>
3135Borland C++ can be downloaded for free from Inprise (Borland)
3136(see their site
3137<A HREF="http://www.borland.com">http://www.borland.com</A>
3138It can compile using a Makefile.  We have supplied this
3139in the source code distrubution as <TT>Makefile.bcc</TT>.
3140You will need to preserve the Unix Makefile by renaming it to, say,
3141<TT>Makefile.unix</TT>, then make a copy of <TT>Makefile.bcc</TT>
3142and call it <TT>Makefile</TT>.  The Makefile is invoked using the
3143<TT>make</TT> command.  If you simply type <TT>make</TT> you
3144will get a list of possible <TT>make</TT> commands.  For example,
3145to compile a single program such as <TT>Dnaml</TT> but not
3146install it, type <TT>make dnaml</TT>.  To compile and install all
3147programs type <TT>make install</TT>.  We have supplied all the
3148the support files and icons needed for the compilations.  They
3149are in subdirectory <TT>bcc</TT> of the main source code
3150directory.  We have had to supply a complete
3151second set of the resource files with names <TT>*.brc</TT>
3152because Borland resource files have a minor incompatibility
3153with Microsoft Visual C++ resource files.
3154<P>
3155If this does not work the <TT>PATH</TT> may need to be set manually.
3156This can be done by opening a Command or DOS window using the Start
3157menu.  To set the path, type
3158<PRE>
3159set BORLAND=Path
3160</PRE>
3161Where <TT>Path</TT> is where Borland is installed, such as
3162<TT>C:\Progra~1\Borland</TT>.
3163Then type
3164<PRE>
3165PATH=%PATH%;%BORLAND%\CBUILD~1\Bin
3166</PRE>
3167<P>
3168<B>Compiling with Metrowerks Codewarrior for Windows</B> 
3169<P>
3170As with Macintosh systems, Metrowerks Codewarrior requires
3171you to have project files for each program you compile.
3172For Metrowerks Codewarrior for Windows we are not providing the projects
3173themselves, but we are providing
3174projects which have been exported as XML files. To open one of these one
3175cannot just click on
3176File/Open but instead on the menu option File/Import Project.
3177Metrowerks will then ask you for the project name.
3178Type in the name of the program (e.g. dnaml). Once this is done Metrowerks will
3179act like this is a regular project file.
3180<P>
3181We have supplied a complete set of these XML project files in the
3182source code distribution.  They are in subdirectory <TT>metro</TT>
3183of the main source code directory.  This is supplied with the
3184source code distribution for Windows (it is not in the source
3185code distributions for other platforms).
3186For Metrowerks Codewarrior for Windows we are not providing the projects
3187themselves, but we are providing
3188projects which have been exported as XML files. To open one of these one
3189cannot just click on
3190File/Open but instead on the menu option File/Import Project.
3191Metrowerks will then ask you for the project name.
3192Type in the name of the program (e.g. dnaml). Once this is done Metrowerks will
3193act like this is a regular project file.
3194<P>
3195To compile the program
3196pull down the <TT>Project</TT> menu and select <TT>Make</TT>.  The
3197program should then compile, possibly with ignorable warning messages.
3198<P>
3199For the moment we are not giving here the details of
3200how to create these projects yourself -- you usually will not need
3201to, as you have the project files we have supplied.
3202<P>
3203<B>Compiling with Cygnus Gnu C++</B>
3204<P>
3205Cygnus Solutions (now a part of Red Hat, Inc.) has adapted the Gnu C compiler
3206to Windows systems and
3207provided an environment, CygWin, which mimics Unix for compiling.
3208This is available for purchase from them, and they also make it
3209available to be downloaded for free.  The download is large.  To get it, go
3210to <A HREF="http://sources.redhat.com/cygwin/download.html">their download site</A> at
3211<CODE>http://sources.redhat.com/cygwin/download.html</CODE> and follow the
3212instructions there.  It is a bit
3213difficult to figure out how to download it -- you need to download
3214their <TT>setup.exe</TT> program and then it will download the rest
3215when it is run.  You will need a lot of disk space for it.
3216<P> 
3217Once you have
3218installed the free Cygnus environment and the associated Gnu C compiler
3219on your Windows system, compiling PHYLIP is essentially identical to
3220what one does for Unix or Linux.  In PHYLIP's <TT>src</TT> directory,
3221change the name of our Unix <TT>Makefile</TT> to something like
3222<TT>Makefile.unx</TT> (so as to keep it around).  There is a special
3223Makefile for the Cygwin
3224compiler called <TT>Makefile.cyg</TT>. Make a copy of it called
3225<TT>Makefile</TT>.
3226<P>
3227This Makefile should contain a compiling command:
3228<P>
3229<TT>CC = gcc</TT>
3230<P>
3231Now enter the Cygwin environment (which you can do using the Windows
3232<TT>Start</TT> menu and its <TT>Programs</TT> menu item.  There should be
3233a <TT>Cygnus</TT> menu choice within that submenu, which you can use to
3234start the Cygnus environment.  This puts you in an imitation of a Unix
3235shell.
3236<P>
3237On entering the CygWin environment you will find yourself in one of the
3238subdirectories of the CygWin directory.  Change to the directory where the
3239PHYLIP programs have been put (for example by issuing the command
3240<P>
3241<TT>cd c:/phylip</TT><BR>
3242<BR>
3243You should then be able to compile PHYLIP
3244by issuing the appropriate make command, such as <TT>make install</TT>.
3245If you have modified one of our source code files such as <TT>dnaml.c</TT>,
3246it would be wise to
3247have saved the original version of it first as, say, <TT>dnaml.c0</TT>.
3248To associate an icon with a program (say DnaML), you need an icon
3249file (say <TT>dna.ico</TT> which contains the icon in standard format.
3250There should also be a file called <TT>dnaml.rc</TT> which contains the single
3251line:
3252<P>
3253<TT>dnaml ICON "dna.ico"</TT>
3254<P>
3255We have provided a subdirectory <TT>icons</TT> in the <TT>src</TT>
3256subdirectory, containing a full set of icons and a full set of resource
3257files (<TT>*.rc</TT>).
3258Our Cygwin Makefile will automatically invoke them.
3259<P>
3260<H3>VMS VAX systems</H3>
3261<P>
3262We have not tried to compile version 3.6 on an OpenVMS system but the
3263following instructions should work.
3264On the OpenVMS operating system with DEC VAX VMS C the programs will compile
3265without alteration.  The commands for compiling a typical program
3266(DNAPARS, which depends on the separately compiled files <TT>phylip.c</TT>
3267and <TT>seq.c</TT>) are:
3268<P>
3269<TT>$ DEFINE LNK$LIBRARY SYS$LIBRARY:VAXCRTL
3270<BR>
3271$ CC DNAPARS.C
3272<BR>
3273$ CC PHYLIP.C
3274<BR>
3275$ CC SEQ.C
3276<BR>
3277$ LINK DNAPARS,PHYLIP,SEQ
3278<BR>
3279</TT>
3280<P>
3281Once you use this <TT>$ DEFINE</TT> statement during a given interactive session,
3282you need not repeat it again as the symbol <TT>LNK$LIBRARY</TT> is thereafter
3283properly defined.  The compilation process leaves a file <TT>DNAPARS.OBJ</TT>
3284in your directory: this can
3285be discarded.  The executable program is named <TT>DNAPARS.EXE</TT>.  To run the program
3286one then uses the command:
3287<P>
3288<TT>$ R DNAPARS</TT>
3289<P>
3290The compiler defaults to the filenames <TT>INFILE.</TT>, <TT>OUTFILE.</TT>, and
3291<TT>TREEFILE.</TT>.
3292If the input file <TT>INFILE.</TT> does not exist the program will prompt you to
3293type in its name.  Note that some commands on VMS such as <TT>TYPE OUTFILE</TT>
3294will fail because the name of the file that it will attempt to type out will be not
3295<TT>OUTFILE.</TT> but <TT>OUTFILE.LIS</TT>.  To get it to type the write file you
3296would have to instead issue the command <TT>TYPE OUTFILE.</TT>.
3297<P>
3298When you are
3299using the interactive previewing feature of DRAWGRAM (or DRAWTREE) on
3300a Tektronix or DEC ReGIS compatible terminal, you will want before
3301running the program to have issued the command:
3302<P>
3303<TT>$ SET TERM/NOWRAP/ESCAPE</TT>
3304<P>
3305so that you do not run into trouble from the VMS line length limit of
3306255 characters or the filtering of escape characters.
3307<P>
3308To know which files to compile together, look at the entries in the
3309<TT>Makefile</TT>.
3310<P>
3311VMS systems are rapidly disappearing, so we will not devote much
3312effort to get PHYLIP working on them.
3313<P>
3314<H3>Parallel computers</H3>
3315<P>
3316As parallel computers become more common, the issue of how to compile
3317PHYLIP for them has become more pressing.  People have been compiling
3318PHYLIP for vector machines and parallel machines for many years.  We
3319have not made a version for parallel machines because there is still
3320no standard parallel programming environment on such machines (or rather,
3321there are many standards, so that one cannot find one that makes
3322a parallel execution version of PHYLIP practical).  However the
3323MPI Message Passing Interface is spreading rapidly, and we will
3324probably support it in future versions of PHYLIP.
3325<P>
3326Although the underlying algorithms of most programs,
3327which treat sites independently, should be amenable to vector and
3328parallel processors,
3329there are details of the code which might best be changed.
3330In certain of the programs (<TT>Dnaml</TT>, <TT>Dnamlk</TT>,
3331<TT>Proml</TT>, <TT>Promlk</TT>) I have put a special
3332comment statement next to the loops in the program where
3333the program will spend most of its time, and which are the places
3334most likely to benefit from parallelization.  This comment statement is:<BR>
3335<PRE>
3336           /* parallelize here */
3337</PRE>
3338In particular
3339within these innermost loops of the programs there are often scalar quantities
3340that are used for temporary bookkeeping.  These quantities, such as
3341<TT>sum1, sum2, zz, z1, yy, y1, aa, bb, cc, sum,</TT> and <TT>denom</TT> in procedure makenewv
3342of DNAML (and similar quantities in procedure nuview) are there to
3343minimize the number of array references.  For vectorizing and parallelizing
3344compilers it will
3345be better to replace them by arrays so that processing can occur
3346simultaneously.
3347<P>
3348If you succeed in making a parallel version of PHYLIP we would like to
3349know how you did it.  In particular, if you can prepare a web page which
3350describes how to do it for your computer system, we would like to have it
3351for inclusion in our PHYLIP web pages.  Please e-mail it to me.  We hope to
3352have a set of pages that give detailed instructions on how to make parallel
3353version of PHYLIP on various kinds of machines.  Alternatively, if we
3354are given your modified version of the program we may be able to
3355figure out how to make modifications to our source code to allow
3356users to compile the program in a way which makes those modifications.
3357<P>
3358<H3>Other computer systems</H3>
3359<P>
3360As you can see from the variety of different systems on which these
3361programs have been successfully run, there are no serious
3362incompatibility problems with most computer systems.  PHYLIP in various
3363past Pascal versions has also been compiled on 8080 and Z80 CP/M Systems, Apple
3364II systems running UCSD Pascal, a variety of minicomputer systems such as
3365DEC PDP-11's and HP 1000's, on 1970's era mainframes such as CDC
3366Cyber systems, and so on.  In a later era
3367it was also compiled on IBM 370 mainframes, and of course on DOS and
3368Windows systems and on Macintosh and PowerMacintosh systems.
3369We have gradually
3370accumulated experience on a wider variety of C compilers.  If you succeed in
3371compiling the C version of PHYLIP on a different machine or a different
3372compiler, I would like to
3373hear the details so that I can consider including the instructions in a future version
3374of this manual.
3375<P>
3376<DIV ALIGN="CENTER">
3377<A NAME="FAQ"><HR><P></A>
3378<H2>Frequently Asked Questions</H2></DIV>
3379<P>
3380This set of Frequently Asked Questions, and their answers, is from the
3381PHYLIP web site.  A more up-to-date version can be found there, at:
3382<P>
3383<DIV ALIGN="CENTER">
3384<A HREF="http://evolution.gs.washington.edu/phylip/faq.html">
3385<TT>http://evolution.gs.washington.edu/phylip/faq.html</TT></A></DIV>
3386<P>
3387<DL>
3388<DT><STRONG>"It doesn't work! <I>It doesn't work!!</I> It says <TT>can't find infile.</TT></STRONG>
3389<DD>Actually, it's working just fine.  Many of the programs look for an input file called <TT>infile</TT>,
3390and if one of that name is not present in the current directory, they then ask
3391you to type in the name of the input file.  That's all that it's doing. This
3392is done so that
3393you can get the program to read the file without you having to type in its
3394name, by making a copy of your input file and calling it <TT>infile</TT>.
3395If you don't do that, then the program issues this message.  It looks
3396alarming, but really all that it is trying to do is to get you to type in
3397the name of the input file.  Try giving it the name of the input file.
3398<DT><STRONG>"The program reads my data file and then says it's has
3399a memory allocation error!"</STRONG>
3400<DD>This is what tends to happen if there is a problem with the format of the data
3401file, so that the programs get confused and think they need to set aside memory
3402for 1,000,000 species or so.  The result is a "memory allocation error".  Check the data file format against the documentation:
3403make sure that the data files have <I>not</I> been saved in the format of
3404your word processor (such as Microsoft Word) but in a "flat ASCII" or "text only"
3405mode.  Note that adding memory to your computer is <I>not</I> the
3406way to solve this problem -- you probably have plenty of memory
3407to run the program once the data file is in the correct format.
3408<DT><STRONG>"On our Macintosh, larger data files fail to run."</STRONG>
3409<DD>We have set the memory allowances on the Macintosh executables
3410to be generous, but not too big.  You therefore may need to
3411increase them.  Use the <TT>Get Info</TT> item on the Finder <TT>File</TT> menu.
3412<DT><STRONG>"I opened the program but I don't see where to create
3413a data file!"</STRONG>
3414<DD>The programs (there are more than one) use data
3415files that have been created outside of the program.  They do not have any
3416data editor within them.  You can create a data file by using an editor,
3417such as Microsoft Word, EMACS, vi, SimpleText, Notepad, etc.  But be sure
3418<I>not</I> to save the file in Microsoft Word's own format.  It should be saved in
3419Text Only format.  You can use the documentation files, including the examples
3420at the end of those files, to figure out the format of the input file.
3421Documentation files such as <TT>main.html</TT>, <TT>sequence.html</TT>,
3422<TT>distance.html</TT> and many others should be consulted.  Many users
3423create their data files by having their alignment program (such as
3424ClustalW), output its alignments in PHYLIP format.  Many alignment programs
3425have options to do that.
3426menu while the program is selected.
3427<DT><STRONG>"I ran PHYLIP, and all it did was say it was extracting a bunch of files!"</STRONG>
3428<DD>
3429There is no executable program
3430named <TT>PHYLIP</TT> in the PHYLIP package!  But in some cases
3431(especially the Windows distribution) there is a file called
3432<TT>phylip.exe</TT>.
3433That file is an archive of documentation and source code.  Once you have
3434run it and extracted the files in it, so that they are in the directory,
3435running it again will just do the extraction again, which is unnecessary.
3436Similarly for the archive files for the Windows executables, which
3437have names like <TT>phylipwx.exe</TT> and <TT>phylipwy.exe</TT>.
3438They are run only once to extract their contents.
3439<DT><STRONG>"One program makes an output file and then the next program crashes while reading it!"</STRONG>
3440<DD>Did you rename the file?  If a program makes a file called <TT>outfile</TT>, and then the
3441next program is told to use <TT>outfile</TT> as its input file, terrible things will
3442happen.  The second program first opens <TT>outfile</TT> as an output file, thus
3443erasing it.  When it then tries to read from this empty <TT>outfile</TT>
3444a psychological
3445crisis ensues.  The solution is simply to rename <TT>outfile</TT> before trying to
3446use it as an input file.
3447<DT><STRONG>"I make a file called infile and then the program can't find it!"</STRONG>
3448<DD>Let me guess.  You are using Windows, right?  You made your file in Word or
3449in Notepad or WordPad, right?  If you made a file in one of these editors, and
3450saved it, not in Word format, but in Text Only format, then you were doing the
3451right thing.  But when you told the operating system to save the file as
3452<TT>infile</TT>, it actually didn't.  It saved it as
3453<TT>infile.txt</TT>. Then just to make
3454life harder for you, the operating system is set up by default to not show
3455that three-letter extension to the file name.  Next to its icon it will show
3456the name <TT>infile</TT>.  So you think, quite reasonably, that
3457there is a file called <TT>infile</TT>.  But there isn't a file of that
3458name, so the program, quite reasonably, can't find a file called
3459<TT>infile</TT>.  If you want to check what the actual file name is, use
3460the <TT>Properties</TT>
3461menu item of the <TT>File</TT> item on your folder (in Windows versions, anyway). 
3462You should be able to get the program to work by telling it that the file name
3463is <TT>INFILE.TXT</TT>.
3464<DT><STRONG>"Consense gives wierd branch lengths! How do I
3465get more reasonable ones?"</STRONG> 
3466<DD>Consense gives branch lengths which are simply the numbers of replicates
3467that support the branch.  This is not a good reflection of how long those
3468branches are estimated to be.  The best way to put better branch lengths on a
3469consensus tree is to use it as a User Tree in a program that will estimate
3470branch lengths for it.  You may need to convert it to being an unrooted tree,
3471using Retree, first.  If the original program you were using was a parsimony
3472program, which does not estimate branch lengths, you may instead have to make
3473some distances between your species (using, for example, DnaDist), and use
3474Fitch to put branch lengths on the user tree.  Here is the sequence of
3475steps you should go through:
3476<OL>
3477<LI>Take the tree and use Retree to make sure it is Unrooted (just
3478read it into Retree and then save it, specifying Unrooted)
3479<LI>Use the unrooted tree as a User Tree (option <TT>U</TT>) in one of
3480our programs (such as Fitch or DnaML).   If you use Fitch, you also
3481need to use one of the distance programs such as DnaDist to
3482compute a set of distances to serve as its input.
3483<LI>Specify that the branch lengths
3484of the tree are not to be used but should be re-estimated.  This
3485is actually the default.
3486</OL>
3487<DT><STRONG>"DrawTree (or DrawGram) doesn't work: it can't find the font file!"</STRONG>
3488<DD>Six font files, called <TT>font1</TT> through <TT>font6</TT>, are
3489distributed with the executables
3490(and with the source code too).  The program looks for a copy of one of them
3491called <TT>fontfile</TT>.  If you haven't made such a copy called
3492<TT>fontfile</TT> it then asks
3493you for the name of the font file.  If they are in the current directory, just
3494type one of <TT>font1</TT> through <TT>font6</TT>.  The reason for
3495having the program look for <TT>fontfile</TT>
3496is so that you can copy your favorite font file, call the copy
3497<TT>fontfile</TT>,
3498and then it will be found automatically without you having to type the name of
3499the font file each time.
3500<DT><STRONG>"Can DrawGram draw a scale beside the tree? Print the branch lengths as numbers?"</STRONG>
3501<DD>It can't do either of these.  Doing so would make the program more complex, and
3502it is not obvious how to fit the branch length numbers into a tree that has
3503many very short internal branches.  If you want these scales or numbers,
3504choose an output plot file format (such as Postscript, PICT or PCX) that can be read by
3505a drawing program such as Adobe Illustrator, Freehand, Canvas, CorelDraw,
3506or MacDraw.
3507Then you can add the scales and branch length numbers yourself by hand.  Note
3508the menu option in DrawTree and DrawGram that specifies the tree size to be
3509a given number of centimeters per unit branch length.
3510<DT><STRONG>"How can I get DrawGram or DrawTree to print the bootstrap values
3511next to the branches?"</STRONG>
3512<DD>When you do bootstrapping and use Consense, it prints the bootstrap
3513values in its output file (both in a table of sets, and on the diagram
3514of the tree which it makes).  These are also in the output tree file of
3515Consense.  There they are in place of branch lengths.  So to get them to
3516be on the output of DrawGram or DrawTree, you must write the tree in the
3517format of a drawing program and use it to put the values in by hand, as
3518mentioned in the answer to the previous question.
3519<DT><STRONG>"I have an HP Laserjet and can't get DrawGram to print on it"</STRONG>
3520<DD>DRAWGRAM and DRAWTREE produce a plot file (called <TT>plotfile</TT>): they
3521do not send it to the printer.  It is up to you to get the plot file to
3522the printer.  If you are running Windows or DOS this can probably be done
3523with the MSDOS command <TT>COPY/B PLOTFILE PRN:</TT>, unless your printer
3524is a networked printer.  The <TT>/B</TT>
3525is important.  If it is omitted the copy command will strip off the
3526highest bit of each byte, which can cause the printing to fail or produce
3527garbage.
3528<DT><STRONG>"DNAML won't read the treefile that is produced by DNAPARS!"</STRONG>
3529<DD>That's because the DnaPars tree file is a rooted tree, and DnaML wants an
3530unrooted tree.  Try using Retree to change the file to be an unrooted tree
3531file.</DD>
3532<DT><STRONG>"In bootstrapping, SEQBOOT makes too large a file"</STRONG>
3533<DD>If there are 1000 bootstrap replicates, it will make a file
35341000 times as long as your original data set.  But for many methods
3535there is another way that uses much less file space.  You can use
3536SEQBOOT to make a file of multiple sets of weights, and use those
3537together with the original data set to do bootstrapping.
3538<DT><STRONG>"In bootstrapping, the output file gets too big."</STRONG>
3539<DD> When running a program such as NEIGHBOR or DNAPARS with multiple data
3540sets (or multiple weights) for purposes of bootstrapping,
3541the output file is usually not needed, as it
3542is the output tree file that is used next.  You can use the menu
3543of the program to turn off the writing of trees into the
3544output file.  The trees will still be written into the tree file.
3545<DT><STRONG>"Why doesn't NEIGHBOR read my DNA sequences correctly?"</STRONG>
3546<DD>Because it  wants
3547to  have as input a distance matrix, not sequences.  You have to use DNADIST to
3548make the distance matrix first.
3549<P>
3550<H3>How to make it do various things</H3>
3551<P>
3552<DT><STRONG>"How do I bootstrap?"</STRONG>
3553<DD>The general method of bootstrapping
3554involves  running  SEQBOOT  to make multiple bootstrapped data sets out of your
3555one data set, then running one of the tree-making programs  with  the  Multiple
3556data  sets option to analyze them all, then running CONSENSE to make a majority
3557rule consensus tree from the resulting tree file.  Read  the  documentation  of
3558SEQBOOT  to  get  further information.  Before, only parsimony methods could be
3559bootstrapped.  With this new system almost any of the  tree-making  methods  in
3560the package can be bootstrapped.  It is somewhat more tedious but you will find
3561it much more rewarding.
3562<DT><STRONG>"How do I specify a multi-species outgroup
3563with your parsimony  programs?"</STRONG> 
3564<DD>It's  not  a  feature  but  is  not too hard to do in many of the programs.  In
3565parsimony programs like MIX, for which the W (Weights) and A (Ancestral states)
3566options are available, and weights can be larger than 1, all you need to do is:
3567<DL COMPACT>
3568<DT><STRONG>(a)</STRONG>
3569<DD>In MIX, make up an extra character with states 0 for  all  the  outgroups
3570and  1  for all the ingroups.  If using DNAPARS the ingroup can have (say)
3571<TT>G</TT> and the outgroup <TT>A</TT>.
3572<DT><STRONG>(b)</STRONG>
3573<DD>Assign this character an enormous weight (such as <TT>Z</TT> for 35) using  the  W
3574option, all other characters getting weight 1, or whatever weight they had
3575before.
3576<DT><STRONG>(c)</STRONG>
3577<DD>If it is available, Use the A (Ancestral states) option to designate that
3578for  that  new  character the state found in the outgroup is the ancestral
3579state.
3580<DT><STRONG>(d)</STRONG>
3581<DD>In MIX do not use the O (Outgroup) option.
3582<DT><STRONG>(e)</STRONG>
3583<DD>After the tree is found, the designated ingroup  should  have  been  held
3584together  by the fake character.  The tree will be rooted somewhere in the
3585outgroup (the program may or may not have a preference for  one  place  in
3586the  outgroup  over  another).  Make sure that you subtract from the total
3587number of steps on the tree all steps in the new character.
3588</DL>
3589<P>
3590In programs like DNAPARS, you cannot use this method as weights  of  sites
3591cannot  be  greater  than  1.   But you do an analogous trick, by adding a
3592largish number of extra sites to the data, with one nucleotide state ("A")
3593for the ingroup and another ("G") for the outgroup.  You will then have to
3594use RETREE to manually reroot the tree in the desired place.
3595<DT><STRONG>"How do I force certain groups to remain  monophyletic in your
3596parsimony programs?"</STRONG> 
3597<DD>By  the same method as in the previous question, using multiple fake characters, any number of
3598groups of species can be forced to be  monophyletic.   In  MOVE,  DOLMOVE,  and
3599DNAMOVE  you  can  specify  whatever  outgroups  you want without going to this
3600trouble.
3601<DT><STRONG>"How can I reroot one of the trees written out by PHYLIP?"</STRONG>
3602<DD>Use the program
3603RETREE.  But keep in mind whether the tree inferred by the original program was
3604already rooted, or whether you are free to reroot it.
3605<DT><STRONG>"What do I do  about  deletions  and  insertions  in  my  sequences?"</STRONG>
3606<DD>The
3607molecular  sequence  programs  will  accept  sequences  that have gaps (the "<TT>-</TT>"
3608character).  They do various things with them,  mostly  not  optimal.   DNAPARS
3609counts  "gap"  as  if it were a fifth nucleotide state (in addition to A, C, G,
3610and T).  Each site counts one change when a  gap  arises  or  disappears.   The
3611disadvantage  of  this  treatment is that a long gap will be overweighted, with
3612one event per gapped site.  So a gap of 10 nucleotides will count as  being  as
3613much  evidence  as  10  single site nucleotide substitutions.  If there are not
3614overlapping gaps, one way to correct this is to recode the first  site  in  the
3615gap  as "<TT>-</TT>" but make all the others be "<TT>?</TT>" so the gap only counts as one event.
3616Other programs such as DNAML and DNADIST count gaps as  equivalent  to  unknown
3617nucleotides  (or  unknown  amino  acids) on the grounds that we don't know what
3618would be there if  something  were  there.   This  completely  leaves  out  the
3619information  from  the presence or absence of the gap itself, but does not bias
3620the gapped sequence to be close  to  or  far  from  other  gapped  or  ungapped
3621sequences.
3622So it is not necessary to remove gapped regions from your
3623sequences, unless the presence of gaps indicates that the region is
3624badly aligned.
3625<DT><STRONG>"How can I produce distances for my data set which
3626has 0's and 1's?"</STRONG> 
3627<DD>You can't do it in a simple and general
3628way, for a straightforward reason.  Distance methods must correct the
3629distances for superimposed changes.  Unless we know specifically how to
3630do this for your particular characters, we cannot accomplish the
3631correction.  There are many formulas we could use, but we can't choose
3632among them without much more information.  There are issues of superimposed
3633changes, as well as heterogeneity of rates of change in different
3634characters.  Thus we have not provided a distance program for 0/1 data.
3635It is up to you to figure out what is an appropriate stochastic model
3636for your data and to find the right distance formulas.
3637<DT><STRONG>"I have RFLP fragment data: which programs should I
3638use?"</STRONG>
3639<DD>This is more difficult question than you may imagine.
3640Here is quick tour of the issues:
3641<UL><LI>You can code fragments are 0 and 1 and use a parsimony program.  It is
3642not obvious in advance whether 0 or 1 is ancestral, though it is likely that
3643change in one direction is more likely than change in the other for each
3644fragment.  One can use either Wagner parsimony (programs <TT>MIX</TT>,
3645<TT>PENNY</TT> or <TT>MOVE</TT>) or use Dollo parsimony
3646(<TT>DOLLOP, DOLPENNY</TT> or <TT>DOLMOVE</TT>)
3647with the ancestral states all set as unknown ("<TT>?</TT>").
3648<LI>You can use a distance matrix method using the RFLP distance of Nei and
3649Li (1979).  Their restriction fragment distance is available in our
3650program RestDist.
3651<LI>You should be very hesitant to bootstrap RFLP's.  The individual
3652fragments do not evolve independently: a single nucleotide substitution
3653can eliminate one fragment and create two (or vice versa).
3654</UL>
3655For restriction <I>sites</I> (rather than fragments) life is a bit
3656easier: they evolve nearly independently so bootstrapping is possible
3657and <TT>RESTML</TT> can be used.  Also directionality of change
3658is less ambiguous when parsimony is used.
3659<DT><STRONG>"Why don't your parsimony programs  print  out  branch  lengths?"</STRONG>
3660<DD>Well, DNAPARS and PARS can.  The others have not yet been upgraded to the
3661same level.  The longer answer is that it is because
3662there  are  problems  defining  the branch lengths.  If you look closely at the
3663reconstructions of the states of the hypothetical ancestral  nodes  for  almost
3664any  data  set  and  almost  any  parsimony method you will find some ambiguous
3665states on those nodes.  There is then usually an ambiguity as to  which  branch
3666the  change  is  actually  on.  Other parsimony programs resolve this in one or
3667another arbitrary fashion, sometimes with the user specifying how (for example,
3668methods  that push the changes up the tree as far as possible or down it as far
3669as possible).  Our older programs leave it to the user to do this.  In
3670DNAPARS and PARS we use an algorithm discovered by Hochbaum and Pathria (1997)
3671(and independently by Wayne Maddison) to compute branch lengths that average
3672over all possible placements of the changes.  But these branch lengths, as
3673nice as they are, do not correct for mulitple superimposed changes.  Few
3674programs  available  from  others  currently  correct  the  branch  lengths for
3675multiple changes of state that may have overlain each other.  One possible  way
3676to  get  branch  lengths  with  nucleotide  sequence  data  is to take the tree
3677topology that you got, use RETREE to convert  it  to  be  unrooted,  prepare  a
3678distance matrix from your data using DNADIST, and then use FITCH with that tree
3679as User Tree and see what branch lengths it estimates.
3680<DT><STRONG>"Why can't your programs handle unordered multistate  characters?"</STRONG>
3681<DD>In this 3.6 release there is a program PARS which does parsimony for
3682undordered multistate characters with up to 8 states, plus <TT>?</TT>.  The
3683other the discrete characters parsimony programs can only handle two states,
3684<TT>0</TT> and <TT>1</TT>.
3685This is mostly because I have not yet had time to modify them to do so  -  the
3686modifications would have to be extensive.  Ultimately I hope to get these done.
3687If you have four or fewer states and need a feature that is not in PARS,
3688you could  recode your states to look like nucleotides
3689and use the parsimony programs in the molecular sequence section of PHYLIP, or
3690you could use one of the excellent parsimony programs produced by others.
3691<P>
3692<H3>Background information needed:</H3>
3693<P>
3694<DT><STRONG>"What file format do I use for the sequences?"<BR>
3695"How do I use the programs?  I can't find any documentation!"</STRONG>
3696<DD>These are discussed in the documentation files.  Do you have them?  If you
3697have a copy of this page you probably do.  They are
3698in a separate archive from the executables (they are in the Documentation and
3699Sources archives, which you should definitely fetch).  Input file formats
3700are discussed in <TT>main.html</TT>, in <TT>sequence.html</TT>, <TT>distance.html</TT>,
3701<TT>contchar.html</TT>, <TT>discrete.html</TT>, and the documentation files for the
3702individual programs.
3703<DT><STRONG>"Where can I find out how to infer
3704phylogenies?</STRONG>
3705<DD>There are few books yet.  For molecular data you could use one of these:
3706<UL>
3707<LI> Graur, D. and W.-H. Li.  2000.  <EM>Fundamentals of Molecular
3708     Evolution.</EM> Sinauer Associates, Sunderland, Massachusetts. (or the earlier edition
3709     by Li and Graur).
3710<LI> Page, R. D. P. and E. C. Holmes.  1998.  <EM>Molecular Evolution:
3711     A Phylogenetic Approach.</EM>  Blackwell, Oxford.
3712<LI> Nei, M. and S. Kumar.  2000.  <EM>Molecular Evolution and
3713     Phylogenetics.</EM> Oxford University Press, Oxford.
3714<LI> Li, W.-H.  1999.  <EM>Molecular Evolution.</EM>  Sinauer Associates,
3715     Sunderland,   Massachusetts.
3716</UL>
3717In addition, one of these three review articles may help:
3718<UL><LI>Swofford, D. L., G. J. Olsen, P. J. Waddell, and D. M. Hillis.  1996.
3719Phylogenetic inference.  pp. 407-514 in <I>Molecular Systematics</I>, 2nd ed.,
3720ed.  D. M. Hillis, C. Moritz, and B. K. Mable.  Sinauer Associates, Sunderland,
3721Massachusetts.
3722<LI>Felsenstein, J. 1988. Phylogenies from molecular sequences: inference and
3723reliability.  <I>Annual Review of Genetics</I> <B>22:</B> 521-565.
3724<LI>Felsenstein, J. 1988. Phylogenies and quantitative
3725characters. <I>Annual Review of Ecology and Systematics</I> <B>19:</B> 445-471.
3726</UL>
3727My own book on phylogenies is due to be published in late 2002.  It
3728will be called "Inferring Phylogenies".  For information on whether it has
3729been published you should check the
3730<A HREF="http://www.sinauer.com">Sinauer Associates web site</A>.
3731<P>
3732<H3>Questions about distribution and citation:</H3>
3733<P>
3734<DT><STRONG>"If I copied PHYLIP from a friend without you knowing, should I try
3735to keep  you from finding out?"</STRONG>
3736<DD>No.  It is to your advantage and mine for you to
3737let me know.  If you did not get PHYLIP "officially" from me  or  from  someone
3738authorized  by me, but copied a friend's version, you are not in my database of
3739users.   You  may also  have  an  old  version  which  has   since   been
3740substantially  improved.  I  don't  mind  you  "bootlegging"
3741PHYLIP (it's free anyway), but
3742you should realize that you may have copied an outdated version. If you are reading this
3743Web page,
3744you can get  the  latest  version  just  as  quickly over Internet.
3745It will help both of us if you get
3746onto my mailing list.  If you are on it, then I will give your  name  to  other
3747nearby  users  when  they ask for the names of nearby users, and they are urged to contact you and
3748update  your  copy.   (I  benefit  by  getting  a  better  feel  for  how  many
3749distributions  there have been, and having a better mailing list to use to give
3750other users local people to contact).  Use the registration form which
3751can be accessed through our web site's registration page.
3752<DT><STRONG>"How do I make a citation  to  the  PHYLIP  package in  the  paper I am
3753writing?"</STRONG> 
3754<DD>One way is like this:
3755<P>
3756Felsenstein, J.  2002.  PHYLIP (Phylogeny Inference Package) version 3.6a3.
3757<I>Distributed by the author.  Department of Genome Sciences, University of
3758Washington, Seattle.</I>
3759<P>
3760or if the editor for whom you are writing insists that the citation must be  to
3761a  printed  publication,  you  could cite a notice for version 3.2 published in
3762Cladistics:
3763<P>
3764Felsenstein, J.  1989.  PHYLIP - Phylogeny Inference Package (Version 3.2).
3765<I>Cladistics</I> <B>5:</B> 164-166.
3766<BR>
3767<P>
3768For a while a printed version of the PHYLIP documentation was available and one
3769could  cite that.  This is no longer true.  Other than that, this is difficult,
3770because I have never written a paper announcing  PHYLIP!   My  1985b  paper  in
3771Evolution on the bootstrap method contains a
3772one-paragraph Appendix describing the availability of this  package,  and  that
3773can  also  be  cited  as  a  reference  for  the  package, although it was
3774distributed since 1980 while the bootstrap paper is 1985.   A paper  on  PHYLIP
3775is needed mostly to give people something to cite, as word-of-mouth, references
3776in other people's papers, and electronic newsgroup  postings  have  spread  the
3777word about PHYLIP's existence quite effectively.
3778<DT><STRONG>"Can I make copies of PHYLIP available to the students in
3779my class?"</STRONG>
3780<DD>Generally, yes.  Read the Copyright notice near the front of
3781this main documentation page.  If you charge money for PHYLIP,
3782or use it in a service for which you charge money, you will need
3783to negotiate a royalty.  But you can make it freely available
3784and you do not need to get any special permission from us to do so.
3785<DT><STRONG>"How many copies of PHYLIP have been distributed?"</STRONG>
3786<DD>On
378727 September, 1996 we reached 5,000 registered installations worldwide.
3788(By now we are well over 15,000 but have lost count for
3789the moment).  Of course there are
3790many more people who have got copies from friends.  PHYLIP is the  most  widely
3791distributed  phylogeny  package. (This situation may reverse itself rapidly
3792once PAUP* is fully released.  During the years it was in full distribution,
3793PAUP was ahead in phylogenies published, and the availability of distance and
3794likelihood methods in PAUP* are making it very popular.)
3795In recent years  magnetic  tape  distribution and e-mail distribution of
3796PHYLIP have disappeared,
3797and there has been a big decrease of diskette distributions (down to only
3798one or two per year).  But all this has
3799been  more  than  offset  by, first, an explosion of distributions by anonymous ftp
3800over Internet, and then a bigger explosion of World Wide Web distributions and
3801registrations (about 6 registrations per day at the moment).
3802<P>
3803<H3>Questions about documentation</H3>
3804<P>
3805<DT><STRONG>"Where can I get a printed version of  the  PHYLIP  documents?"</STRONG>
3806<DD>For  the
3807moment,  you  can  only  get  a  printed  version by printing it yourself.  For
3808versions 3.1 to 3.3 a printed version was sold by Christopher Meacham  and  Tom
3809Duncan,  then  at  the  University Herbarium of the University of California at
3810Berkeley.  But they have had to discontinue this as it was too much work.   You
3811should  be  able to print out the documentation files on almost any printer and
3812make yourself a printed version of whichever of them you need.
3813<DT><STRONG>"Why have I been dropped from your newsletter mailing list?"</STRONG>
3814<DD>You haven't.
3815The  newsletter  was  dropped.  It simply was too hard to mail it out to such a
3816large mailing list.  The last issue of the newsletter  was  Number  9  in  May,
38171987.  The Listserver News Bulletins that we tried for a while have also been dropped
3818as too hard to keep up to date.  I am hoping that our World Wide Web site will take their place.
3819</DL>
3820<P>
3821<DIV ALIGN="CENTER">
3822<H3>Additional Frequently Asked Questions, or:</B>
3823"Why didn't it occur to you to ...</H3></DIV>
3824<DL>
3825<DT><STRONG>... allow the options to be set on the command line?</STRONG>
3826<DD>We could in Unix and Linux, or somewhat differently in Windows.  But
3827there are so many options that this would be difficult, especially
3828when the options require additional information to be supplied such as
3829rates of evolution for many categories of sites.  You may be asking this
3830question because you want to automate the operation of PHYLIP programs
3831using batch files (command files) to run in background.  If that is the
3832issue, see the section of this main documentation page on
3833"Running the programs in background or under control of a command file".
3834It explains how to set the options using input redirection and a file
3835that has the menu responses as keystrokes.
3836<DT><STRONG>... write these programs in Pascal?"</STRONG>
3837<DD>These programs started out
3838in Pascal in 1980.  In 1993 we released both Pascal and C versions.  The
3839present version (3.6) and
3840future versions will be C-only.  I make fewer mistakes in Pascal and do
3841like the language better than C, but C has overtaken Pascal and Pascal
3842compilers are starting to be hard to find on some machines.  Also C is a
3843bit better standardized which makes the number of modifications a user
3844has to make to adapt the programs to their system much less.
3845<DT><STRONG>... write these programs in Java?"</STRONG>
3846<DD>Well, we might.  It is not completely clear which of two contenders,
3847C++ and Java, will become more widespread, and which one will gradually
3848fade away.  Whichever one is more successful, we will probably want to use
3849for future versions of PHYLIP.  As the C compilers that are used to
3850compile PHYLIP are usually also able to compile C++, we will be moving in
3851that direction, but with constant worrying about whether to convert PHYLIP
3852to Java instead.</DD>
3853<DT><STRONG>... forgot about all those inferior systems and just develop PHYLIP for Unix?"</STRONG>
3854<DD>This is self-answering, since the same people first said I should
3855just develop it for Apple II's, then for CP/M Z-80's, then for IBM PCDOS,
3856then for Macintoshes or for Sun
3857workstations, and then for Windows.  If I had listened to them and done any one of these, I would
3858have had a very hard time adapting the package to any of the other ones once
3859these folks changed their mind (and most of them did)!
3860<DT><STRONG>... write these programs in PROLOG
3861(or Ada, or Modula-2, or SIMULA, or BCPL, or PL/I, or APL, or LISP)?"</STRONG>
3862<DD>These are all languages I have considered.  All
3863have advantages, but they are not really widespread (as are C and C++).
3864<DT><STRONG>... include in the package a program to do the Distance Wagner method, (or
3865successive approximations character weighting,
3866or transformation series analysis)?"</STRONG>
3867<DD>In most cases where I have not
3868included other methods, it is because I decided that they had no substantial
3869advantages over methods that were included (such as the programs FITCH,
3870KITSCH, NEIGHBOR, the <TT>T</TT> option of MIX and DOLLOP, and the "<TT>?</TT>" ancestral
3871states option of the discrete characters parsimony programs).
3872<DT><STRONG>... include in the package ordination methods and more
3873clustering algorithms?"</STRONG>
3874<DD>Because this is <I>not</I> a clustering package, it's a
3875package for phylogeny estimation.  Those are different tasks with different
3876objectives and mostly different methods.  Mary Kuhner and Jon Yamato have,
3877however,
3878included in NEIGHBOR an option for UPGMA clustering, which will be very
3879similar to KITSCH in results.
3880<DT><STRONG>... include in the package a program to do nucleotide sequence
3881alignment?"</STRONG>
3882<DD>Well, yes, I should
3883have, and this is scheduled to be in future releases.  But multiple sequence
3884alignment programs, in the era after Sankoff, Morel, and Cedergren's 1973
3885classic paper, need to use substantial computer horsepower to estimate the
3886alignment and the tree together (but see Karl Nicholas's program
3887<TT>GeneDoc</TT> or Ward Wheeler and David Gladstein's <TT>MALIGN</TT>, as
3888well as more approximate methods of tree-based alignment used in
3889<TT>ClustalW</TT> or <TT>TreeAlign</TT>).
3890</DL>
3891<P>
3892<DIV ALIGN="CENTER">
3893<H3>(Fortunately) obsolete questions</H3></DIV>
3894<P>
3895(The following four questions, once
3896common, have finally disappeared, I am pleased to report).
3897<H4>"Why didn't it occur to you to ...</H4></DIV>
3898<DL>
3899<DT><STRONG>... let me log in to your computer in Seattle
3900and copy the files out over a phone line?"</STRONG>
3901<DD>No thanks.  It would cost you for a lot of
3902long-distance telephone time, plus a half hour of my time and yours in which
3903I had to explain to you how to log in and do the copying.
3904<DT><STRONG>... send me a listing of your program?"</STRONG>
3905<DD>Damn it, it's not "a program",
3906it's 35 programs, in a great many files.  What were you
3907thinking of doing, having 1800-line programs typed in by slaves at your
3908end?  If you were going to go to all that trouble why not try network
3909transfer?  If you have these then you can print out all the
3910listings you want to and add them to the huge stack of printed output in
3911the corner of your office.
3912<DT><STRONG>... write a magnetic tape in our computer center's favorite format
3913(inverted Lithuanian EBCDIC at 998 bpi)?"</STRONG>
3914<DD>Because the ANSI standard
3915format is the most widely used one, and even though your computer center
3916may pretend it can't read a tape written this way, if you sniff around
3917you will find a utility to read it.  It's just a <I>lot</I> easier for me to
3918let you do that work.  If I tried to put the tape into your format, I
3919would probably get it wrong anyway.
3920<DT><STRONG>... give us a version of these in FORTRAN?"</STRONG>
3921<DD>Because the
3922programs are <I>far</I> easier to write and debug in C or Pascal, and cannot
3923easily be
3924rewritten into FORTRAN (they make extensive use of recursive calls and
3925of records and pointers).  In any case, C is widely available.  If you don't
3926have a C compiler or don't know
3927how to use it, you are going to have to learn a language like C or
3928Pascal sooner or later, and the sooner the better.
3929</DL>
3930<P>
3931<A NAME="newfeatures"><HR><P></A>
3932<DIV ALIGN="CENTER">
3933<H2>New Features in This Version</H2></DIV>
3934<P>
3935Version 3.6 has many new features:
3936<UL><LI>Faster (well, less, slow) likelihood programs.
3937<LI>The DNA and protein likelihood and distance programs allow
3938for rate variation between sites using a gamma distribution of
3939rates among sites, or using a gamma distribution plus a given
3940fraction of sites which are assumed invariant.
3941<LI>A new multistate discrete characters parsimony program, PARS, that
3942handles unordered multistate characters.
3943<LI>The DNAPARS and PARS parsimony programs can infer multifurcating
3944trees, which sensibly reduces the number of tied trees they find.
3945<LI>A new protein sequence likelihood program, <TT>PROML</TT>,
3946and also a version, <TT>PROMLK</TT> which assumes a molecular clock.
3947<LI>A new restriction sites and restriction fragments distance program,
3948<TT>RESTDIST</TT>, that can also be used to compute distances for RAPD and
3949AFLP data.  It also allows for gamma-distributed rate variation among
3950DNA sites.
3951<LI>In the DNA likelihood programs, you can now specify different
3952categories of rates of change (such as rates for first, second, and
3953third positions of a coding sequence) and assign them to specific sites.
3954This is in addition to the ability of the program to use the Hidden Markov
3955Model mechanism to allow rates of change to vary across sites in a way that
3956does not ask you to assign which rate goes with which site.
3957<LI>The input files for many of the programs are now
3958simpler, in that they do not contain options information such as specification
3959of weights and categories.  That information is now provided in separete
3960files with default names such as <TT>weights</TT> and <TT>categories</TT>.
3961<LI>The DNA likelihood programs can now evaluate multifurcating
3962user trees (option <TT>U</TT>).
3963<LI>All programs that read in user-defined trees now do so from a separate
3964file, whose default name is <TT>intree</TT>, rather than requiring them to
3965be in the input file as before.
3966<LI>The DNA likelihood programs can infer the sequence at ancestral
3967nodes in the interior of the tree.
3968<LI>DNAPARS can now do transversion parsimony.
3969<LI>The bootstrapping program SEQBOOT now can, instead of producing a
3970large file containing multiple data sets, be asked instead
3971to produce a weights file with multiple sets of weights.  Many
3972programs in this release can analyze those multiple weights together with
3973the original data set, which saves disk space.
3974<LI>The bootstrapping program SEQBOOT can pass weights and categories
3975information through to a multiple weights file or a multiple categories
3976file.
3977<LI>SEQBOOT can also convert sequence files from Interleaved to
3978Sequential form, or back.
3979<LI>SEQBOOT can also write a sequence data file into a preliminary version of
3980a new XML format which is being defined for sequence alignments,
3981for use by programs that need XML input
3982(none of the current PHYLIP programs yet need this format, but it
3983will be useful in the future).
3984<LI>RETREE can now write tree out into a preliminary version of a new XML tree
3985file format which is in the process of being defined.
3986<LI>The Kishino-Hasegawa-Templeton (KHT) test which compares user-defined
3987trees (option U) is now joined by the Shimodaira-Hasegawa (SH) test
3988(Shimodaira and Hasegawa, 1999) which corrects for comparisons among
3989multiple tests.  This avoids a statistical problem with multiple user trees.
3990<LI>CONTRAST can now carry out an analysis that takes into account
3991within-species variation, according to a model similar (but not
3992identical) to that introduced by Michael Lynch (1990)
3993<LI>A new program, TREEDIST, computes the Robinson-Foulds symmetric
3994difference distance among trees.  This measures the number of branches in
3995the trees that are present in one but not the other.
3996<LI>FITCH and KITSCH now have an option to make trees by the
3997minimum evolution distance matrix method.
3998<LI>The protein parsimony program PROTPARS now allows you to choose among
3999a number of different genetic codes such as mitochondrial codes.
4000<LI>The consensus tree program CONSENSE
4001can compute the M<SUB>l</SUB> family of consensus tree methods, which
4002generalize the Majority Rule consensus tree method. It can
4003also compute our extended Majority Rule consensus (which is
4004Majority Rule with some additional groups added to resolve the
4005tree more completely), and it can also compute the original
4006Majority Rule consensus tree method which does not add these
4007extra groups.  It can also
4008compute the Strict consensus.
4009<LI>The tree-drawing programs DRAWGRAM and DRAWTREE have a number of new
4010options of kinds of file they can produce, including Windows Bitmap files,
4011files for the Idraw and FIG X windows drawing programs, the POV ray-tracer,
4012and even VRML Virtual Reality Markup Language files that will enable you
4013to wander around the tree using a VRML plugin for your browser, such as
4014Cosmo Player.
4015<LI>DRAWTREE now uses my new Equal Daylight Algorithm to draw unrooted
4016trees.  This gives a much better-looking tree.  Of course, competing programs
4017such as TREEVIEW and PAUP draw trees that look just as good - because they
4018too have started to use my method (with my encouragement).  DRAWTREE also
4019can use another algorithm, the n-body method.
4020<LI>The tree-drawing programs can now produce trees across multiple
4021pages, which is handy for looking at trees with very large numbers
4022of tips, and for producing giant diagrams by pasting together
4023multiple sheets of paper.
4024</UL>
4025<P>
4026There are many more, lesser features added as well.
4027<P>
4028<A NAME="future"><HR><P></A>
4029<DIV ALIGN="CENTER">
4030<H2>Coming Attractions, Future Plans</H2></DIV>
4031<P>
4032There are some obvious deficiencies in this version.  Some of these
4033holes will be filled in the next few releases (leading to version
40344.0).  They include:
4035<OL>
4036<LI>A program to align molecular sequences on a predefined User Tree may
4037ultimately be included.  This will allow alignment and phylogeny
4038reconstruction to procede iteratively by successive runs of two programs, one
4039aligning on a tree and the other finding a better tree based on that alignment.
4040In the shorter run a simple two-sequence alignment program may be included.
4041<LI>An interactive "likelihood explorer" for DNA sequences will be written.
4042This will allow, either with or without the assumption of a molecular
4043clock, trees to be varied interactively so that the user can get a much
4044better feel for the shape of the likelihood surface.  Likelihood will be
4045able to be plotted against branch lengths for any branch.
4046<LI>If possible we will find some way of correcting for purine/pyrimidine
4047richness variations among species, within the framework of the maximum
4048likelihood programs.  That they maximum likelihood programs do not allow
4049for base composition variation is their major limitation at the moment.
4050<LI>The Hidden Markov Model (regional rates) option of DNAML and DNAMLK will
4051be generalized to allow
4052for rates at sites to gradually change as one moves along the tree,
4053in an attempt to implement Fitch and Markowitz's (1970) notion of "covarions".
4054<LI>Obviously we need to start thinking about a more visual mouse/windows
4055interface, but only if that can be used on X windows, Macintoshes, and
4056Windows.
4057<LI>Program PENNY and its relatives will improved so as to run faster
4058and find all most parsimonious trees more quickly.
4059<LI>A more sophisticated compatibility program should be included, if I can
4060find one.
4061<LI>An "evolutionary clock" version of CONTML will be done, and the same
4062may also be done for RESTML.
4063<LI>We are gradually generalizing the tree structures in the programs to
4064infer multifurcating trees as well as bifurcating ones.
4065We should be able to have any program read any tree and know what to do
4066with it, without the user having to fret about whether an unrooted tree was
4067fed to a program that needs a rooted tree.
4068<LI>We are economizing on the size of the source code, and enforcing some
4069standardization of it, by putting frequently used routines in separate
4070files which can be linked into various programs.  This will enforce
4071a rather complete standardization of our code.
4072<LI>We will move our code to an object-oriented
4073language, most lkely C++.  One could describe the language that version
40743.4 was written in as "Pascal", version 3.5 as "Pascal written in C",
4075version 3.6 as "C written in C", and maybe version 4.0 as "C++ written
4076in C" and then 4.1 as "C++ written in C++".  At least that scenario
4077is one possibility.
4078</OL>
4079<P>
4080Much of the future development of the package will be in the DNA and protein
4081likelihood programs and the distance matrix programs.  This is for several
4082reasons.  First, I am more interested in those problems.  Second, collection of
4083molecular data is increasing rapidly, and those programs have the most promise
4084for future development
4085for those data.
4086<P>
4087<A NAME="endorsements"><HR><P></A>
4088<DIV ALIGN="CENTER">
4089<H2>Endorsements</H2></DIV>
4090<P>
4091Here are some comments people have made in print about PHYLIP.  Explanatory
4092material in square brackets is my own.  They fall naturally into two groups:
4093<P>
4094<H3>From the pages of <I>Cladistics</I>:</H3>
4095<P>
4096<BLOCKQUOTE>
4097"Under no circumstances can we recommend PHYLIP/WAG [their name for the
4098Wagner parsimony option of MIX]."
4099<DIV ALIGN="RIGHT">
4100Luckow, M. and R. A. Pimentel (1985)
4101</DIV>
4102</BLOCKQUOTE>
4103<P>
4104<BLOCKQUOTE>
4105"PHYLIP has not proven very effective in implementing parsimony (Luckow and
4106Pimentel, 1985)."
4107<DIV ALIGN="RIGHT">
4108J. Carpenter (1987a)
4109</DIV>
4110</BLOCKQUOTE>
4111<P>
4112<BLOCKQUOTE>
4113"... PHYLIP.  This is the computer program where every newsletter concerning
4114it is mostly bug-catching, some of which have been put there by previous
4115corrections.  As Platnick (1987) documents, through dint of much labor useful
4116results may be attained with this program, but I would suggest an
4117easier way: FORMAT b:"
4118<DIV ALIGN="RIGHT">
4119J. Carpenter (1987b)
4120</DIV>
4121</BLOCKQUOTE>
4122<P>
4123<BLOCKQUOTE>
4124"PHYLIP is bug-infested and both less effective and orders of
4125magnitude slower than other programs ...."
4126<DIV ALIGN="RIGHT">
4127"T. N. Nayenizgani" [J. S. Farris] (1990)
4128</DIV>
4129</BLOCKQUOTE>
4130<P>
4131<BLOCKQUOTE>
4132"Hennig86 [by J. S. Farris] provides such substantial improvements over
4133previously available programs (for both mainframes and microcomputers) that
4134it should now become the tool of choice for practising systematists."
4135<DIV ALIGN="RIGHT">
4136N. Platnick (1989)
4137</DIV>
4138</BLOCKQUOTE>
4139<P>
4140<H3>... and in the pages of other journals:</H3>
4141<P>
4142<BLOCKQUOTE>
4143"The availability, within PHYLIP of distance, compatibility, maximum likelihood,
4144and generalized `invariants' algorithms (Cavender and Felsenstein, 1987) sets
4145it apart from other packages .... One of the strengths of PHYLIP is its
4146documentation ...."
4147<DIV ALIGN="RIGHT">
4148Michael J. Sanderson (1990)
4149</DIV>
4150<EM>(Sanderson also criticizes PHYLIP for slowness and inflexibility of its
4151parsimony algorithms, and compliments other packages on their strengths).</EM>
4152</BLOCKQUOTE>
4153<P>
4154<BLOCKQUOTE>
4155"This package of programs has gradually become a basic necessity to anyone
4156working seriously on various aspects of phylogenetic inference .... The package
4157includes more programs than any other known phylogeny package.  But it is not
4158just a collection of cladistic and related programs.  The package has great
4159value added to the whole, and for this it is unique and of extreme
4160importance .... its various strengths are in the great array of methods
4161provided ...."
4162<DIV ALIGN="RIGHT">
4163Bernard R. Baum (1989)
4164</DIV>
4165</BLOCKQUOTE>
4166<P>
4167(note also W. Fink's critical remarks (1986) on version 2.8 of PHYLIP).
4168<P>
4169<A NAME="references"><HR><P></A>
4170<DIV ALIGN="CENTER">
4171<H2>References for the Documentation Files</H2></DIV>
4172<P>
4173In the documentation files that follow I frequently refer to papers
4174in the literature.  In order to centralize the references they are given
4175in this section.  The chapter by David Swofford,
4176Gary Olsen, Peter Waddell, and David Hillis
4177(1996) is also an excellent review of the issues in phylogeny
4178reconstruction.
4179If you want to find further papers beyond these, my
4180Quarterly Review of Biology review of 1982 and my Annual Review of Genetics
4181review of 1988 list many further references.
4182<P>
4183Adams, E. N.  1972.  Consensus techniques and the comparison of
4184taxonomic trees.  <I>Systematic Zoology</I> <B>21:</B> 390-397.
4185<P>
4186Adams, E. N.  1986.  N-trees as nestings: complexity, similarity, and
4187consensus.  <I>Journal of Classification</I> <B>3:</B> 299-317.
4188<P>
4189Archie, J. W.  1989.  A randomization test for phylogenetic information in
4190systematic data.  <I>Systematic Zoology</I> <B>38:</B> 219-252.
4191<P>
4192Barry, D., and J. A. Hartigan.  1987.  Statistical analysis of hominoid
4193molecular evolution.  <I>Statistical Science</I>  <B>2:</B> 191-210.
4194<P>
4195Baum, B. R.  1989.  PHYLIP: Phylogeny Inference Package. Version 3.2. (Software
4196review).  <I>Quarterly Review of Biology</I> <B>64:</B> 539-541.
4197<P>
4198Bron, C., and J. Kerbosch.  1973.  Algorithm 457: Finding all cliques
4199of an undirected graph.  <I>Communications of the Association for Computing Machinery</I> <B>16:</B> 575-577.
4200<P>
4201Camin, J. H., and R. R. Sokal.  1965.  A method for deducing branching
4202sequences in phylogeny.  <I>Evolution</I> <B>19:</B> 311-326.
4203<P>
4204Carpenter, J.  1987a.  A report on the Society for the Study of Evolution
4205workshop "Computer Programs for Inferring Phylogenies".  <I>Cladistics</I> <B>3:</B>
4206363-375.
4207<P>
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4589Templeton, A. R.  1983.  Phylogenetic inference from restriction endonuclease
4590cleavage site maps with particular reference to the evolution of humans and the
4591apes. <I>Evolution</I> <B>37:</B> 221-244.
4592<P>
4593Thompson, E. A.  1975.  <I>Human Evolutionary Trees.</I>  Cambridge University
4594Press, Cambridge.
4595<P>
4596Wu, C. F. J.  1986.  Jackknife, bootstrap and other resampling plans in
4597regression analysis.  <I>Annals of Statistics</I> <B>14:</B> 1261-1295.
4598<P>
4599Yang, Z. 1993.  Maximum-likelihood estimation of phylogeny from DNA sequences
4600when substitution rates differ over sites.  <I>Molecular Biology and
4601Evolution</I> <B>10:</B> 1396-1401.
4602<P>
4603Yang, Z. 1994.  Maximum likelihood phylogenetic estimation from DNA sequences
4604with variable rates over sites: approximate methods.  <I>Journal of Molecular
4605Evolution</I> <B>39:</B> 306-314.
4606<P>
4607Yang, Z.  1995.  A space-time process model for the evolution of DNA sequences.
4608<I>Genetics</I> <B>139:</B> 993-1005.
4609<P>
4610<DIV ALIGN="CENTER">
4611<H2>Credits</H2></DIV>
4612<P>
4613Over the years various granting agencies have contributed to the
4614support of the PHYLIP project (at first without knowing it).  They are:
4615<P>
4616<TABLE CELLPADDING=3 BORDER="1">
4617<TR><TD ALIGN="LEFT">Years</TD>
4618<TD ALIGN="LEFT">Agency</TD>
4619<TD ALIGN="LEFT">Grant or Contract Number</TD>
4620</TR>
4621<TR><TD ALIGN="LEFT">1999-2002</TD>
4622<TD ALIGN="LEFT">NSF</TD>
4623<TD ALIGN="LEFT">BIR-9527687</TD>
4624</TR>
4625<TR><TD ALIGN="LEFT">1999-2002</TD>
4626<TD ALIGN="LEFT">NIH NIGMS</TD>
4627<TD ALIGN="LEFT">R01 GM51929-04</TD>
4628</TR>
4629<TR><TD ALIGN="LEFT">1999-2001</TD>
4630<TD ALIGN="LEFT">NIH NIMH</TD>
4631<TD ALIGN="LEFT">R01 HG01989-01</TD>
4632</TR>
4633<TR><TD ALIGN="LEFT">1995-1999</TD>
4634<TD ALIGN="LEFT">NIH NIGMS</TD>
4635<TD ALIGN="LEFT">R01 GM51929-01</TD>
4636</TR>
4637<TR><TD ALIGN="LEFT">1992-1995 </TD>
4638<TD ALIGN="LEFT">National Science Foundation</TD>
4639<TD ALIGN="LEFT">DEB-9207558</TD>
4640</TR>
4641<TR><TD ALIGN="LEFT">1992-1994</TD>
4642<TD ALIGN="LEFT">NIH NIGMS Shannon Award</TD>
4643<TD ALIGN="LEFT">2 R55 GM41716-04</TD>
4644</TR>
4645<TR><TD ALIGN="LEFT">
46461989-1992</TD>
4647<TD ALIGN="LEFT">NIH NIGMS</TD>
4648<TD ALIGN="LEFT">1 R01-GM41716-01</TD>
4649</TR>
4650<TR><TD ALIGN="LEFT">
46511990-1992</TD>
4652<TD ALIGN="LEFT">National Science Foundation</TD>
4653<TD ALIGN="LEFT">BSR-8918333</TD>
4654</TR>
4655<TR><TD ALIGN="LEFT">
46561987-1990</TD>
4657<TD ALIGN="LEFT">National Science Foundation</TD>
4658<TD ALIGN="LEFT">BSR-8614807</TD>
4659</TR>
4660<TR><TD ALIGN="LEFT">1979-1987</TD>
4661<TD ALIGN="LEFT">U.S. Department of Energy</TD>
4662<TD ALIGN="LEFT">DE-AM06-76RLO2225 TA DE-AT06-76EV71005</TD>
4663</TR>
4664</TABLE>
4665<P>
4666I am particularly grateful to program administrators William Moore,
4667Irene Eckstrand, Peter Arzberger, and Conrad Istock, who have
4668gone beyond the call of duty to make sure that PHYLIP continued.
4669<P>
4670Booby prizes for funding are awarded to:
4671<UL><LI>The people at the U.S. Department of Energy who, in 1987, decided they
4672were "not interested in phylogenies",
4673<LI>The members of the Systematics Panel of NSF who twice (in 1989 and 1992)
4674positively recommended that my applications <I>not</I> be funded.  I am very
4675grateful to program director William Moore for courageously overruling
4676their decision the first time.  The 1992 NSF Systematics Panel could claim
4677no credit for PHYLIP whatsoever.
4678<LI>The members of the 1992 Genetics Study Section of NIH who rated my
4679proposal in the 53rd percentile (I don't know if that's 53rd from
4680the top or the bottom, but does it matter?), thus denying it funding.  I am,
4681however, grateful to the NIGMS administrators, especially Irene Eckstrand,
4682who supported giving me
4683a "Shannon award" partially funding my work for a period in spite of this
4684rating.
4685</UL>
4686<P>
4687The original Camin-Sokal parsimony program and the polymorphism parsimony
4688program were written by me in 1977 and 1978.  They were Pascal versions of
4689earlier FORTRAN programs I wrote in 1966 and 1967 using the same algorithm to
4690infer phylogenies under the Camin-Sokal and polymorphism parsimony
4691criteria.  Harvey Motulsky worked for me as a programmer in 1971 and wrote
4692FORTRAN programs to carry out the Camin-Sokal, Dollo, and polymorphism
4693methods (he is known these days as the author of the scientific
4694graphing package GraphPad).  But most of the early work on PHYLIP other than my own was by Jerry
4695Shurman and Mark Moehring.  Jerry Shurman worked for me in the summers of
46961979 and 1980, and Mark Moehring worked for me in the summers of 1980 and
46971981.  Both wrote original versions of many of the other programs, based on
4698the original versions of my Camin-Sokal parsimony program and POLYM.  These
4699formed the basis of Version 1 of the Package, first distributed in October,
47001980.
4701<P>
4702Version 2, released in the spring of 1982, involved a fairly complete rewrite
4703by me of many of those programs.  Hisashi Horino for
4704version 3.3 reworked some parts of the programs CLIQUE and CONSENSE
4705to make their output more comprehensible, and has added some code to the
4706tree-drawing programs DRAWGRAM and DRAWTREE as well.  He also worked on
4707some of the Drawtree and Drawgram driver code.
4708<P>
4709My more recent part-time programmers Akiko Fuseki, Sean Lamont,
4710Andrew Keeffe, Daniel Yek, Dan Fineman, Patrick Colacurcio,
4711Mike Palczewski, and Doug Buxton gave
4712me substantial help with the current release, and their excellent work is
4713greatly appreciated.  Akiko in particular did much of the hard work of adding
4714new features and changing old ones in the 3.4 and 3.5 releases,
4715centralized many of the C routines in support files, and is responsible for the
4716new versions of DNAPARS and PARS. Andrew
4717prepared the Macintosh version, wrote RETREE, added the ray-tracing
4718and PICT code to the DRAW programs and has since done much other work.  Sean
4719was central to the conversion to
4720C, and tested it extensively.  My postdoctoral fellow
4721Mary Kuhner and her associate Jon Yamato created NEIGHBOR, the
4722neighbor-joining and UPGMA program, for the current release, for which I am
4723also grateful (Naruya Saitou and Li Jin kindly encouraged us to use some of the
4724code from their own implementation of this method).
4725<P>
4726I am very grateful to over 200
4727users for algorithmic suggestions, complaints about features (or lack of
4728features), and information about the behavior of their operating systems
4729and compilers.  A list of some of their names will be found at the credits page
4730on the PHYLIP web site.
4731<P>
4732A major contribution to this package has been made by others
4733writing programs or parts of programs.  Chris Meacham contributed the
4734important program FACTOR, long demanded by users, and the even more
4735important ones PLOTREE and PLOTGRAM.  Important parts of the code in
4736DRAWGRAM and DRAWTREE were taken over from those two programs.
4737Kent Fiala wrote
4738function "reroot" to do outgroup-rooting, which was an essential part of many
4739programs in earlier versions.  Someone at the Western Australia Institute of
4740Technology suggested the name PHYLIP (by writing it the label on the
4741outside of a magnetic tape), but they all seem to deny having done
4742so (and I've lost the relevant letter).
4743<P>
4744The distribution of the package also owes much to Buz Wilson and Willem Ellis,
4745who put a lot of effort into the early distributions of the PCDOS and
4746Macintosh versions respectively.  Christopher Meacham and Tom Duncan for three
4747versions distributed a printed version of these documentation files (they are no
4748longer able to do so), and I am
4749very grateful to them for those efforts.  William H.E. Day and F. James Rohlf
4750have been very helpful in setting up the listserver news bulletin service which
4751succeeded the PHYLIP newsletter for a time.
4752<P>
4753I also wish to thank the people who have made computer resources available to
4754me, mostly in the loan of use of microcomputers.  These include Jeremy
4755Field, Clem Furlong, Rick Garber, Dan Jacobson, Rochelle Kochin, Monty Slatkin,
4756Jim Archie, Jim Thomas, and George Gilchrist.
4757<P>
4758I should also note the computers used to develop this package:
4759These include a CDC 6400, two DECSystem 1090s, my trusty old SOL-20, my
4760old Osborne-1, a VAX 11/780, a VAX 8600, a MicroVAX I, a DECstation
47613100, my old Toshiba 1100+, my
4762DECstation 5000/200, a DECstation 5000/125, a Compudyne 486DX/33, a
4763Trinity Genesis 386SX, a Zenith Z386, a Mac Classic, a DEC Alphastation 400
47644/233, a Pentium 120, a Pentium 200, a PowerMac 6100, and a Macintosh G3.
4765(One of the reasons
4766we have been successful in achieving compatibility between different computer
4767systems is that I have had to run them myself under so many different operating
4768systems and compilers).
4769<P>
4770<A NAME="otherprograms"><HR><P></A>
4771<DIV ALIGN="CENTER">
4772<H2>Other Phylogeny Programs Available Elsewhere</H2></DIV>
4773<P>
4774A comprehensive list of phylogeny programs is maintained at the PHYLIP
4775web site on the Phylogeny Programs pages:
4776<P>
4777<DIV ALIGN="CENTER">
4778<FONT SIZE=+2><A HREF="http://evolution.gs.washington.edu/phylip/software.html">
4779<TT>http://evolution.gs.washington.edu/phylip/software.html</TT></FONT></A></DIV>
4780<P>
4781Here we will simply mention some of the major general-purpose programs.  For
4782many more and much more, see those web pages.
4783<P>
4784<B>PAUP*</B>&nbsp;&nbsp;  A comprehensive program with parsimony, likelihood, and
4785distance matrix methods.  It competes with PHYLIP to be responsible for
4786the most trees published.  Written by David Swofford and distributed by
4787Sinauer Associates of Sunderland, Massachusetts.
4788It is described in a web pages for
4789<A HREF="http://www.sinauer.com/detail.php?id=8060">the Macintosh version,</A>
4790<A HREF="http://www.sinauer.com/detail.php?id=8079">the Windows version,</A>
4791and
4792<A HREF="http://www.sinauer.com/detail.php?id=8044">the Unix/OpenVMS version.</A>
4793Current prices are $100 for the Macintosh version, $85 for the
4794Windows version, and $150 for Unix versions for many kinds of workstations.
4795<P>
4796<B>MacClade</B>&nbsp;&nbsp;   An interactive Macintosh and PowerMac program to
4797rearrange trees and watch the changes in the fit of the trees to
4798data as judged by parsimony.  MacClade has a great many features including
4799a spreadsheet data editor and many different descriptive statistics
4800for different kinds of data.  It is particularly designed to export and
4801import data to and from PAUP*.
4802MacClade is available for $100 from Sinauer Associates, of Sunderland,
4803Massachusetts.  It is described in a web page at
4804<A HREF="http://www.sinauer.com/detail.php?id=4707">
4805<TT>http://www.sinauer.com/detail.php?id=4707</TT></A>.
4806MacClade is also described on its <A HREF="http://phylogeny.arizona.edu/macclade/macclade.html">
4807Web page</A>, at <CODE>http://phylogeny.arizona.edu/macclade/macclade.html</CODE
4808>.
4809<P>
4810<B>MEGA</B>&nbsp;&nbsp;  A Windows and DOS program by Sudhir Kumar of Arizona State University
4811(written together with Koichiro Tamura and Masatoshi Nei while he was a
4812student in Nei's lab at Pennsylvania
4813State University).  It can carry out parsimony and distance matrix methods
4814for DNA sequence data.  Version 2.1 for Windows
4815can be downloaded from <A HREF="http://www.megasoftware.net">
4816the MEGA web site</A>
4817at <TT>http://www.megasoftware.net</TT>.
4818<P>
4819<B>PAML</B>&nbsp;&nbsp;  Ziheng Yang of the Department of Genetics and Biometry at
4820University College, London has written this package of programs to
4821carry out likelihood analysis of DNA and protein sequence data.  PAML is
4822particularly strong in the options for coping with variability of rates
4823of evolution from site to site, though it is less able than some other
4824packages to search effectively for the best tree.  It is available as
4825C source code and as PowerMac and Windows executables from its web site at
4826<A HREF="http://abacus.gene.ucl.ac.uk/software/paml.html">
4827<TT>http://abacus.gene.ucl.ac.uk/software/paml.html</TT></A>.
4828<P>
4829<B>TREE-PUZZLE</B>&nbsp;&nbsp;  This package by Korbinian Strimmer and Arndt von Haeseler
4830was begun when they were at the Uviversit&auml;t Munchen in Germany.
4831TREE-PUZZLE can carry out likelihood
4832methods for DNA and protein data, searching by the strategy of
4833"quartet puzzling" which they invented.  It can also compute distances.
4834It superimposes trees estimated
4835from many quartets of species.  TREE-PUZZLE is available for Unix, Macintoshes,
4836or Windows from their web site at
4837<A HREF="http://www.tree-puzzle.de/"><TT>http://www.tree-puzzle.de/</TT></A>.
4838<P>
4839<B>DAMBE</B> &nbsp;&nbsp; A package written by Xuhua Xia, then of the
4840Department of
4841Ecology and Biodiversity of the University of Hong Kong.
4842Its initials stand for Data Analysis in Molecular Biology and Evolution.
4843DAMBE is a general-purpose package for DNA and protein sequence phylogenies.
4844It can read and
4845convert a number of file formats, and has many features for
4846descriptive statistics, and can compute a number of commonly-used
4847distance matrix measures and infer phylogenies by parsimony, distance,
4848or likelihood methods, including bootstrapping and jackknifing.  There are
4849a number of kinds of statistical tests of trees available and it
4850can also display phylogenies.  DAMBE includes a copy of ClustalW as well;
4851DAMBE consists of Windows95 executables.  It is available from its
4852web site at <A HREF="http://web.hku.hk/~xxia/software/software.htm">
4853<CODE>http://web.hku.hk/~xxia/software/software.htm</CODE></A>.
4854Xia has now moved to the Department of Biology of the University of Ottawa,
4855Canada, and I suspect the DAMBE web site will soon follow him there.
4856<P>
4857<B>MOLPHY</B>&nbsp;&nbsp;  A package of programs for carrying out likelihood analysis
4858of DNA and protein data, written by Jun Adachi and Masami Hasegawa of the
4859Institute of Statistical Mathematics in Tokyo, Japan.  The source code
4860is available from them at
4861<A HREF="http://www.ism.ac.jp/software/ismlib/softother.e.html">
4862the MOLPHY web site</A> at
4863<CODE>http://www.ism.ac.jp/software/ismlib/softother.e.html</CODE>, and
4864Windows executables are available from Russell Malmberg's web site at
4865<A HREF="http://dogwood.botany.uga.edu/malmberg/software.html">
4866<TT>http://dogwood.botany.uga.edu/malmberg/software.html</TT></A>.
4867<P>
4868<B>Hennig86</B>&nbsp;&nbsp;  A fast parsimony program by J. S. Farris of the
4869Naturhistoriska Riksmuseet in Stockholm, Sweden for discrete characters
4870data (it can handle DNA if its states are recoded to be digits).
4871Reputed to be faster than PAUP*.
4872The program is distributed as an executable and costs $50, plus $5
4873mailing costs ($10 outside of of the U.S.). The user's name should be stated,
4874as copies are personalized as a copy-protection measure. It is
4875distributed by Arnold Kluge, Amphibians and Reptiles, Museum of Zoology,
4876University of
4877Michigan, Ann Arbor, Michigan 48109-1079, U.S.A. (<TT>akluge@umich.edu</TT>) and
4878by Diana Lipscomb at George Washington University (<TT>BIODL@gwuvm.gwu.edu</TT>).
4879<P>
4880<B>RnA</B>&nbsp;&nbsp;  J. S. Farris's very fast program which uses parsimony
4881to carry out jackknifing resampling of DNA sequence data.  This would be
4882nearly equivalent in properties to bootstrapping if the jackknifing were
4883sampling random halves of the data, but Farris prefers to have each
4884jackknife sample delete a fraction 1/<I>e</I> of the data, which will give
4885most groups too much support (he would disagree with this statement).
4886RnA is available from Arnold Kluge, Amphibians and Reptiles, Museum of Zoology,
4887University of
4888Michigan, Ann Arbor, Michigan 48109-1079, U.S.A. (<TT>akluge@umich.edu</TT>)
4889and Diana Lipscomb
4890at George Washington University (<TT>BIODL@gwuvm.gwu.edu</TT>) who may be
4891contacted for details.  The cost is about $30 US.
4892<P>
4893<B>NONA</B>&nbsp;&nbsp;  Pablo Goloboff, of the Instituto Miguel Lillo in
4894Tucuman, Argentina has written these very fast parsimony programs, capable
4895of some relevant forms of weighted parsimony, which can handle either
4896DNA sequence data or discrete characters.  It is available as shareware
4897from <A HREF="http://www.cladistics.com/aboutNona.htm">
4898<TT>http://www.cladistics.com/aboutNona.htm</TT></A>
4899There is a 30 day free trial, after which
4900NONA must be purchased separately by sending a check for $40.00 to
4901either directly to the the author, or to: James M. Carpenter, Attn: NONA,
4902Division of Invertebrate Zoology, American Museum of Natural History,
4903Central Park West at 79th Street, New York, NY 10024.
4904<P>
4905<B>TNT</B> This program, by Pablo Goloboff, J. S. Farris, and Kevin Nixon,
4906is for searching large data sets for most parsimonious trees.
4907The authors are respectively at the Instituto Miguel Lillo in Tucuman,
4908Argentina, the Naturhistoriska Riksmuseet in Stockholm, Sweden, and the
4909Hortorium, Cornell University, Ithaca, New York.
4910TNT is described
4911as faster than other methods, though not faster than NONA for small to
4912medium data sets.  Its distribution status is somewhat uncertain.  The site
4913<A HREF="http://www.cladistics.com/aboutTNT.html">
4914<TT>http://www.cladistics.com/aboutTNT.html</TT></A>
4915describes it as unavailable,
4916while the web site <A HREF="http://www.cladistics.com/webtnt.html">
4917<TT>http://www.cladistics.com/webtnt.html</TT></A> makes a beta version
4918available for download.  The program downloaded is free but needs a password to
4919function, which the user should obtain from Pablo Goloboff (see the latter
4920web page for details).
4921<P>
4922These are only a few of the more than 194 different phylogeny packages that
4923are now available (as of January, 2001 - the number keeps increasing).  The
4924others are described (and web links and ftp addresses provided) at my
4925Phylogeny Programs web pages at the address given above.
4926<P>
4927<A NAME="helpme"><HR><P></A>
4928<DIV ALIGN="CENTER">
4929<H2>How You Can Help Me</H2></DIV>
4930<P>
4931Simply let me know of any problems you have had adapting the
4932programs to your computer.  I can often make "transparent" changes that, by
4933making the code avoid the wilder, woolier, and less standard parts of
4934C, not only help others who have your machine but even improve the
4935chance of the programs functioning on new machines.  I would like fairly
4936detailed information on what gave trouble, on what operating system,
4937machine, and (if relevant) compiler, and what had to be done to make the
4938programs work.  I am sometimes able to do some over-the-telephone
4939trouble-shooting, particularly
4940if I don't have to pay for the call, but electronic mail is a the best
4941way for me to be asked about problems, as you can include your
4942input and output files so I can see what is going on (please do <EM>not</EM>
4943send them as Attachments, but as part of the body of a message).  I'd really
4944like these programs to be
4945able to run with only routine changes on <I>absolutely everything</I>, down to
4946and possibly including the Amana Touchmatic Radarange Microwave Oven
4947which was an Intel 8080 system (in fact, early versions of this package did
4948run successfully on Intel 8080 systems running the CP/M operating system).
4949A PalmPilot version is contemplated too.
4950<P>
4951I would also like to know timings of programs from the package, when
4952run on the three test input files provided above, for various computer and
4953compiler combinations, so that I can provide this information in the
4954section on speeds of this document.
4955<P>
4956For the phylogeny plotting programs DRAWGRAM and DRAWTREE,
4957I am particularly interested in knowing what has to be done
4958to adapt them for other graphic file formats.
4959<P>
4960You can also be helpful to PHYLIP users in your part of the world by
4961helping them get the latest version of PHYLIP from our web site
4962and by helping them with any
4963problems they may have in getting PHYLIP working on their data.
4964<P>
4965Your help is appreciated.  I am always happy to hear suggestions
4966for features and programs that ought to be incorporated in the package,
4967but please do not be upset if I turn out to have already considered the
4968particular possibility you suggest and decided against it.
4969<P>
4970<A NAME="trouble"><HR><P></A>
4971<DIV ALIGN="CENTER">
4972<H2>In Case of Trouble</H2></DIV>
4973<P>
4974<I>Read The (documentation) Files Meticulously</I> ("RTFM").  If that doesn't solve the
4975problem, please check the Frequently Asked Questions web page at the
4976PHYLIP web site:
4977<P>
4978<FONT SIZE=+2>
4979<TT><A HREF="http://evolution.gs.washington.edu/phylip/faq.html">
4980http://evolution.gs.washington.edu/phylip/faq.html</TT></A></FONT>
4981<P>
4982and the PHYLIP Bugs web page at that site:
4983<P>
4984<FONT SIZE=+2>
4985<TT><A HREF="http://evolution.gs.washington.edu/phylip/bugs.html">
4986http://evolution.gs.washington.edu/phylip/bugs.html</TT></A></FONT>
4987<P>
4988If none of these answers your question, get in touch with me.  My electronic mail address
4989is given below.  If you do ask about a problem, please specify the program
4990name, version of the package, computer operating system, and
4991send me your data file so I can test the problem.  Do <I>not</I>
4992send your data file as an e-mail Attachment but instead
4993as the body of a message. I read the e-mail on a Unix system, which makes
4994it impossible to read some formats of attachments without
4995running around to other machines and moving the files there. This
4996is one of my least favorite activities, so please do not use attachments.
4997Also it will help if you
4998have the relevant output and documentation files so that you
4999can refer to them in any correspondence.  I can also be reached by telephone
5000by calling me in my office:
5001+1-(206)-543-0150, or at home: +1-(206)-526-9057 (how's <I>that</I> for user
5002support!).  If I cannot be reached at either place, a message can be left at
5003the office of
5004the Department of Genome Sciences, (206)-221-7377 but I prefer strongly that I not
5005call you, as in any phone consultation the least you can do is pay the phone
5006bill.  Better yet, use electronic mail.
5007<P>
5008Particularly if you are in a part of the world distant from me, you may also
5009want to try to get in touch with other users of PHYLIP nearby.  I can also,
5010if requested, provide a list of nearby users.
5011<P>
5012<DIV ALIGN="RIGHT">
5013<TABLE><TR><TD ALIGN=LEFT>
5014Joe Felsenstein<BR>
5015Department of Genome Sciences<BR>
5016University of Washington<BR>
5017Box 357730<BR>
5018Seattle, Washington 98195-7730, U.S.A.
5019</TD></TR></TABLE>
5020</DIV>
5021<P>
5022Electronic mail addresses: &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;<TT>joe@gs.washington.edu</TT>
5023<BR><HR>
5024</BODY>
5025</HTML>
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