
                                 fgendist 



Function

   Compute genetic distances from gene frequencies

Description

   Computes one of three different genetic distance formulas from gene
   frequency data. The formulas are Nei's genetic distance, the
   Cavalli-Sforza chord measure, and the genetic distance of Reynolds et.
   al. The former is appropriate for data in which new mutations occur in
   an infinite isoalleles neutral mutation model, the latter two for a
   model without mutation and with pure genetic drift. The distances are
   written to a file in a format appropriate for input to the distance
   matrix programs.

Algorithm

   This program computes any one of three measures of genetic distance
   from a set of gene frequencies in different populations (or species).
   The three are Nei's genetic distance (Nei, 1972), Cavalli-Sforza's
   chord measure (Cavalli- Sforza and Edwards, 1967) and Reynolds, Weir,
   and Cockerham's (1983) genetic distance. These are written to an
   output file in a format that can be read by the distance matrix
   phylogeny programs FITCH and KITSCH.

   The three measures have somewhat different assumptions. All assume
   that all differences between populations arise from genetic drift.
   Nei's distance is formulated for an infinite isoalleles model of
   mutation, in which there is a rate of neutral mutation and each mutant
   is to a completely new alleles. It is assumed that all loci have the
   same rate of neutral mutation, and that the genetic variability
   initially in the population is at equilibrium between mutation and
   genetic drift, with the effective population size of each population
   remaining constant.

   Nei's distance is:


                                      \   \
                                      /_  /_  p1mi   p2mi
                                       m   i
           D  =  - ln  ( ------------------------------------- ).

                           \   \                \   \
                         [ /_  /_  p1mi2]1/2   [ /_  /_  p2mi2]1/2
                            m   i                m   i

   where m is summed over loci, i over alleles at the m-th locus, and
   where

     p1mi

   is the frequency of the i-th allele at the m-th locus in population 1.
   Subject to the above assumptions, Nei's genetic distance is expected,
   for a sample of sufficiently many equivalent loci, to rise linearly
   with time.

   The other two genetic distances assume that there is no mutation, and
   that all gene frequency changes are by genetic drift alone. However
   they do not assume that population sizes have remained constant and
   equal in all populations. They cope with changing population size by
   having expectations that rise linearly not with time, but with the sum
   over time of 1/N, where N is the effective population size. Thus if
   population size doubles, genetic drift will be taking place more
   slowly, and the genetic distance will be expected to be rising only
   half as fast with respect to time. Both genetic distances are
   different estimators of the same quantity under the same model.

   Cavalli-Sforza's chord distance is given by


                   \               \                        \
     D2    =    4  /_  [  1   -    /_   p1mi1/2 p 2mi1/2]  /  /_  (am  - 1)
                    m               i                        m

   where m indexes the loci, where i is summed over the alleles at the
   m-th locus, and where a is the number of alleles at the m-th locus. It
   can be shown that this distance always satisfies the triangle
   inequality. Note that as given here it is divided by the number of
   degrees of freedom, the sum of the numbers of alleles minus one. The
   quantity which is expected to rise linearly with amount of genetic
   drift (sum of 1/N over time) is D squared, the quantity computed
   above, and that is what is written out into the distance matrix.

   Reynolds, Weir, and Cockerham's (1983) genetic distance is


                       \    \
                       /_   /_  [ p1mi     -  p2mi]2
                        m    i
       D2     =      --------------------------------------

                         \               \
                      2  /_   [  1   -   /_  p1mi    p2mi ]
                          m               i

   where the notation is as before and D2 is the quantity that is
   expected to rise linearly with cumulated genetic drift.

   Having computed one of these genetic distances, one which you feel is
   appropriate to the biology of the situation, you can use it as the
   input to the programs FITCH, KITSCH or NEIGHBOR. Keep in mind that the
   statistical model in those programs implicitly assumes that the
   distances in the input table have independent errors. For any measure
   of genetic distance this will not be true, as bursts of random genetic
   drift, or sampling events in drawing the sample of individuals from
   each population, cause fluctuations of gene frequency that affect many
   distances simultaneously. While this is not expected to bias the
   estimate of the phylogeny, it does mean that the weighing of evidence
   from all the different distances in the table will not be done with
   maximal efficiency. One issue is which value of the P (Power)
   parameter should be used. This depends on how the variance of a
   distance rises with its expectation. For Cavalli-Sforza's chord
   distance, and for the Reynolds et. al. distance it can be shown that
   the variance of the distance will be proportional to the square of its
   expectation; this suggests a value of 2 for P, which the default value
   for FITCH and KITSCH (there is no P option in NEIGHBOR).

   If you think that the pure genetic drift model is appropriate, and are
   thus tempted to use the Cavalli-Sforza or Reynolds et. al. distances,
   you might consider using the maximum likelihood program CONTML
   instead. It will correctly weigh the evidence in that case. Like those
   genetic distances, it uses approximations that break down as loci
   start to drift all the way to fixation. Although Nei's distance will
   not break down in that case, it makes other assumptions about equality
   of substitution rates at all loci and constancy of population sizes.

   qThe most important thing to remember is that genetic distance is not
   an abstract, idealized measure of "differentness". It is an estimate
   of a parameter (time or cumulated inverse effective population size)
   of the model which is thought to have generated the differences we
   see. As an estimate, it has statistical properties that can be
   assessed, and we should never have to choose between genetic distances
   based on their aesthetic properties, or on the personal prestige of
   their originators. Considering them as estimates focuses us on the
   questions which genetic distances are intended to answer, for if there
   are none there is no reason to compute them. For further perspective
   on genetic distances, I recommend my own paper evaluating Reynolds,
   Weir, and Cockerham (1983), and the material in Nei's book (Nei,
   1987).

Usage

   Here is a sample session with fgendist


% fgendist 
Compute genetic distances from gene frequencies
Phylip gendist program input file: gendist.dat
Phylip gendist program output file [gendist.fgendist]: 

Distances calculated for species
    European     .
    African      ..
    Chinese      ...
    American     ....
    Australian   .....

Distances written to file "gendist.fgendist"

Done.


   Go to the input files for this example
   Go to the output files for this example

Command line arguments

   Standard (Mandatory) qualifiers:
  [-infile]            frequencies File containing one or more sets of data
  [-outfile]           outfile    [*.fgendist] Phylip gendist program output
                                  file

   Additional (Optional) qualifiers:
   -method             menu       [n] Which method to use (Values: n (Nei
                                  genetic distance); c (Cavalli-Sforza chord
                                  measure); r (Reynolds genetic distance))
   -[no]progress       boolean    [Y] Print indications of progress of run
   -lower              boolean    [N] Lower triangular distance matrix

   Advanced (Unprompted) qualifiers: (none)
   Associated qualifiers:

   "-outfile" associated qualifiers
   -odirectory2        string     Output directory

   General qualifiers:
   -auto               boolean    Turn off prompts
   -stdout             boolean    Write standard output
   -filter             boolean    Read standard input, write standard output
   -options            boolean    Prompt for standard and additional values
   -debug              boolean    Write debug output to program.dbg
   -verbose            boolean    Report some/full command line options
   -help               boolean    Report command line options. More
                                  information on associated and general
                                  qualifiers can be found with -help -verbose
   -warning            boolean    Report warnings
   -error              boolean    Report errors
   -fatal              boolean    Report fatal errors
   -die                boolean    Report dying program messages

acdDelPhyloFreq '0'

Input file format

   fgendist reads continuous character data

  Continuous character data

   The programs in this group use gene frequencies and quantitative
   character values. One (CONTML) constructs maximum likelihood estimates
   of the phylogeny, another (GENDIST) computes genetic distances for use
   in the distance matrix programs, and the third (CONTRAST) examines
   correlation of traits as they evolve along a given phylogeny.

   When the gene frequencies data are used in CONTML or GENDIST, this
   involves the following assumptions:
    1. Different lineages evolve independently.
    2. After two lineages split, their characters change independently.
    3. Each gene frequency changes by genetic drift, with or without
       mutation (this varies from method to method).
    4. Different loci or characters drift independently.

   How these assumptions affect the methods will be seen in my papers on
   inference of phylogenies from gene frequency and continuous character
   data (Felsenstein, 1973b, 1981c, 1985c).

   The input formats are fairly similar to the discrete-character
   programs, but with one difference. When CONTML is used in the
   gene-frequency mode (its usual, default mode), or when GENDIST is
   used, the first line contains the number of species (or populations)
   and the number of loci and the options information. There then follows
   a line which gives the numbers of alleles at each locus, in order.
   This must be the full number of alleles, not the number of alleles
   which will be input: i. e. for a two-allele locus the number should be
   2, not 1. There then follow the species (population) data, each
   species beginning on a new line. The first 10 characters are taken as
   the name, and thereafter the values of the individual characters are
   read free-format, preceded and separated by blanks. They can go to a
   new line if desired, though of course not in the middle of a number.
   Missing data is not allowed - an important limitation. In the default
   configuration, for each locus, the numbers should be the frequencies
   of all but one allele. The menu option A (All) signals that the
   frequencies of all alleles are provided in the input data -- the
   program will then automatically ignore the last of them. So without
   the A option, for a three-allele locus there should be two numbers,
   the frequencies of two of the alleles (and of course it must always be
   the same two!). Here is a typical data set without the A option:

     5    3
2 3 2
Alpha      0.90 0.80 0.10 0.56
Beta       0.72 0.54 0.30 0.20
Gamma      0.38 0.10 0.05  0.98
Delta      0.42 0.40 0.43 0.97
Epsilon    0.10 0.30 0.70 0.62

   whereas here is what it would have to look like if the A option were
   invoked:

     5    3
2 3 2
Alpha      0.90 0.10 0.80 0.10 0.10 0.56 0.44
Beta       0.72 0.28 0.54 0.30 0.16 0.20 0.80
Gamma      0.38 0.62 0.10 0.05 0.85  0.98 0.02
Delta      0.42 0.58 0.40 0.43 0.17 0.97 0.03
Epsilon    0.10 0.90 0.30 0.70 0.00 0.62 0.38

   The first line has the number of species (or populations) and the
   number of loci. The second line has the number of alleles for each of
   the 3 loci. The species lines have names (filled out to 10 characters
   with blanks) followed by the gene frequencies of the 2 alleles for the
   first locus, the 3 alleles for the second locus, and the 2 alleles for
   the third locus. You can start a new line after any of these allele
   frequencies, and continue to give the frequencies on that line
   (without repeating the species name).

   If all alleles of a locus are given, it is important to have them add
   up to 1. Roundoff of the frequencies may cause the program to conclude
   that the numbers do not sum to 1, and stop with an error message.

   While many compilers may be more tolerant, it is probably wise to make
   sure that each number, including the first, is preceded by a blank,
   and that there are digits both preceding and following any decimal
   points.

   CONTML and CONTRAST also treat quantitative characters (the
   continuous-characters mode in CONTML, which is option C). It is
   assumed that each character is evolving according to a Brownian motion
   model, at the same rate, and independently. In reality it is almost
   always impossible to guarantee this. The issue is discussed at length
   in my review article in Annual Review of Ecology and Systematics
   (Felsenstein, 1988a), where I point out the difficulty of transforming
   the characters so that they are not only genetically independent but
   have independent selection acting on them. If you are going to use
   CONTML to model evolution of continuous characters, then you should at
   least make some attempt to remove genetic correlations between the
   characters (usually all one can do is remove phenotypic correlations
   by transforming the characters so that there is no within-population
   covariance and so that the within-population variances of the
   characters are equal -- this is equivalent to using Canonical
   Variates). However, this will only guarantee that one has removed
   phenotypic covariances between characters. Genetic covariances could
   only be removed by knowing the coheritabilities of the characters,
   which would require genetic experiments, and selective covariances
   (covariances due to covariation of selection pressures) would require
   knowledge of the sources and extent of selection pressure in all
   variables.

   CONTRAST is a program designed to infer, for a given phylogeny that is
   provided to the program, the covariation between characters in a data
   set. Thus we have a program in this set that allow us to take
   information about the covariation and rates of evolution of characters
   and make an estimate of the phylogeny (CONTML), and a program that
   takes an estimate of the phylogeny and infers the variances and
   covariances of the character changes. But we have no program that
   infers both the phylogenies and the character covariation from the
   same data set.

   In the quantitative characters mode, a typical small data set would
   be:

     5   6
Alpha      0.345 0.467 1.213  2.2  -1.2 1.0
Beta       0.457 0.444 1.1    1.987 -0.2 2.678
Gamma      0.6 0.12 0.97 2.3  -0.11 1.54
Delta      0.68  0.203 0.888 2.0  1.67
Epsilon    0.297  0.22 0.90 1.9 1.74

   Note that in the latter case, there is no line giving the numbers of
   alleles at each locus. In this latter case no square-root
   transformation of the coordinates is done: each is assumed to give
   directly the position on the Brownian motion scale.

   For further discussion of options and modifiable constants in CONTML,
   GENDIST, and CONTRAST see the documentation files for those programs.

  Input files for usage example

  File: gendist.dat

    5    10
2 2 2 2 2 2 2 2 2 2
European   0.2868 0.5684 0.4422 0.4286 0.3828 0.7285 0.6386 0.0205
0.8055 0.5043
African    0.1356 0.4840 0.0602 0.0397 0.5977 0.9675 0.9511 0.0600
0.7582 0.6207
Chinese    0.1628 0.5958 0.7298 1.0000 0.3811 0.7986 0.7782 0.0726
0.7482 0.7334
American   0.0144 0.6990 0.3280 0.7421 0.6606 0.8603 0.7924 0.0000
0.8086 0.8636
Australian 0.1211 0.2274 0.5821 1.0000 0.2018 0.9000 0.9837 0.0396
0.9097 0.2976

Output file format

   fgendist output simply contains on its first line the number of
   species (or populations). Each species (or population) starts a new
   line, with its name printed out first, and then and there are up to
   nine genetic distances printed on each line, in the standard format
   used as input by the distance matrix programs. The output, in its
   default form, is ready to be used in the distance matrix programs.

  Output files for usage example

  File: gendist.fgendist

    5
European    0.000000  0.078002  0.080749  0.066805  0.103014
African     0.078002  0.000000  0.234698  0.104975  0.227281
Chinese     0.080749  0.234698  0.000000  0.053879  0.063275
American    0.066805  0.104975  0.053879  0.000000  0.134756
Australian  0.103014  0.227281  0.063275  0.134756  0.000000

Data files

   None

Notes

   None.

References

   None.

Warnings

   None.

Diagnostic Error Messages

   None.

Exit status

   It always exits with status 0.

Known bugs

   None.

See also

   Program name                        Description
   egendist     Genetic Distance Matrix program
   fcontml      Gene frequency and continuous character Maximum Likelihood

Author(s)

   This program is an EMBOSS conversion of a program written by Joe
   Felsenstein as part of his PHYLIP package.

   Although we take every care to ensure that the results of the EMBOSS
   version are identical to those from the original package, we recommend
   that you check your inputs give the same results in both versions
   before publication.

   Please report all bugs in the EMBOSS version to the EMBOSS bug team,
   not to the original author.

History

   Written (2004) - Joe Felsenstein, University of Washington.

   Converted (August 2004) to an EMBASSY program by the EMBOSS team.

Target users

   This program is intended to be used by everyone and everything, from
   naive users to embedded scripts.
