
                                 eprotpars 



Function

   Conversion of PHYLIP's protpars

Description

   EPROTPARS -- Embossified Protein Sequence Parsimony Method

   This program infers an unrooted phylogeny from protein sequences,
   using a new method intermediate between the approaches of Eck and
   Dayhoff (1966) and Fitch (1971). Eck and Dayhoff (1966) allowed any
   amino acid to change to any other, and counted the number of such
   changes needed to evolve the protein sequences on each given
   phylogeny. This has the problem that it allows replacements which are
   not consistent with the genetic code, counting them equally with
   replacements that are consistent. Fitch, on the other hand, counted
   the minimum number of nucleotide substitutions that would be needed to
   achieve the given protein sequences. This counts silent changes
   equally with those that change the amino acid.

   The present method insists that any changes of amino acid be
   consistent with the genetic code so that, for example, lysine is
   allowed to change to methionine but not to proline. However, changes
   between two amino acids via a third are allowed and counted as two
   changes if each of the two replacements is individually allowed. This
   sometimes allows changes that at first sight you would think should be
   outlawed. Thus we can change from phenylalanine to glutamine via
   leucine in two steps total. Consulting the genetic code, you will find
   that there is a leucine codon one step away from a phenylalanine
   codon, and a leucine codon one step away from glutamine. But they are
   not the same leucine codon. It actually takes three base substitutions
   to get from either of the phenylalanine codons UUU and UUC to either
   of the glutamine codons CAA or CAG. Why then does this program count
   only two? The answer is that recent DNA sequence comparisons seem to
   show that synonymous changes are considerably faster and easier than
   ones that change the amino acid. We are assuming that, in effect,
   synonymous changes occur so much more readily that they need not be
   counted. Thus, in the chain of changes UUU (Phe) --> CUU (Leu) --> CUA
   (Leu) --> CAA (Glu), the middle one is not counted because it does not
   change the amino acid (leucine).

   To maintain consistency with the genetic code, it is necessary for the
   program internally to treat serine as two separate states (ser1 and
   ser2) since the two groups of serine codons are not adjacent in the
   code. Changes to the state "deletion" are counted as three steps to
   prevent the algorithm from assuming unnecessary deletions. The state
   "unknown" is simply taken to mean that the amino acid, which has not
   been determined, will in each tree that is evaluated be assumed be
   whichever one causes the fewest steps.

   The assumptions of this method (which has not been described in the
   literature), are thus something like this:

       1.  Change in different sites is independent.

       2.  Change in different lineages is independent.

       3.  The probability of a base substitution that changes the  amino  acid
          sequence  is  small  over the lengths of time involved in a branch of
          the phylogeny.

       4.  The  expected  amounts  of  change  in  different  branches  of  the
          phylogeny  do  not  vary  by  so much that two changes in a high-rate
          branch are more probable than one change in a low-rate branch.

       5.  The expected amounts of change do not vary enough among  sites  that
          two changes in one site are more probable than one change in another.

       6.  The probability of a base change that is synonymous is  much  higher
          than the probability of a change that is not synonymous.

   That these are the assumptions of parsimony methods has been
   documented in a series of papers of mine: (1973a, 1978b, 1979, 1981b,
   1983b, 1988b). For an opposing view arguing that the parsimony methods
   make no substantive assumptions such as these, see the works by Farris
   (1983) and Sober (1983a, 1983b, 1988), but also read the exchange
   between Felsenstein and Sober (1986).

   The protein sequences are given by the one-letter code used by
   described in the Molecular Sequence Programs documentation file. Note
   that if two polypeptide chains are being used that are of different
   length owing to one terminating before the other, they should be coded
   as (say)

             HIINMA*????
             HIPNMGVWABT

   since after the stop codon we do not definitely know that there has
   been a deletion, and do not know what amino acid would have been
   there. If DNA studies tell us that there is DNA sequence in that
   region, then we could use "X" rather than "?". Note that "X" means an
   unknown amino acid, but definitely an amino acid, while "?" could mean
   either that or a deletion. The distinction is often significant in
   regions where there are deletions: one may want to encode a six-base
   deletion as "-?????" since that way the program will only count one
   deletion, not six deletion events, when the deletion arises. However,
   if there are overlapping deletions it may not be so easy to know what
   coding is correct.

   One will usually want to use "?" after a stop codon, if one does not
   know what amino acid is there. If the DNA sequence has been observed
   there, one probably ought to resist putting in the amino acids that
   this DNA would code for, and one should use "X" instead, because under
   the assumptions implicit in this parsimony method, changes to any
   noncoding sequence are much easier than changes in a coding region
   that change the amino acid, so that they shouldn't be counted anyway!

Usage

   Here is a sample session with eprotpars using the data:-
     5    10
Alpha     ABCDEFGHIK
Beta      AB--EFGHIK
Gamma     ?BCDSFG.??
Delta     CIKDEFGHIK
Epsilon   DIKDEFGHIK


% eprotpars

Command line arguments

  eprotpars

Data files

Notes

   Multiple sequences sets not implemented yet!.

References

Warnings

Diagnostics

Exit status

Known bugs

See also

Author(s)

   (c) Copyright 1986-1993 by Joseph Felsenstein and by the University of
   Washington. Written by Joseph Felsenstein. Permission is granted to
   copy this document provided that no fee is charged for it and that
   this copyright notice is not removed.

   This application was modified for inclusion in EMBOSS by Ian Longden
   (il@sanger.ac.uk) Informatics Division, The Sanger Centre, Wellcome
   Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.

Priority

Target users

Comments
