use strict; use warnings; $|=1; my @aa=('A','R','N','D','C','Q','E','G','H','I','L','K','M','F','P','S','T','W','Y','V'); #PAM1 #Mutation probability matrix for the evolutionary distance of 1 PAM (i.e., one Accepted Point Mutation per 100 amino acids). #An element of this matrix, [Mij], gives the probability that the amino acid in column j will be replaced by the amino acid #in row i after a given evolutionary interval, in this case 1 PAM. (Adapted from Figure 82. Atlas of Protein Sequence and Structure, Suppl 3, 1978, M.O. Dayhoff, ed. National Biomedical Research Foundation, 1979.) #Thus, there is a 0.56% probability that Asp will be replaced by Glu. #%PAM calculated from upper PAM1 table #Hash Key states from AA1 to AA2 eg. AE means change of changing/evolving from A to E. #Figures are in percentages (DE = 0.56) my 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,0,"YA",0.02000400080016,"YR",0,"YN",0.0400080016003201,"YD",0,"YC",0.03000600120024,"YQ",0,"YE",0.01000200040008,"YG",0,"YH",0.0400080016003201,"YI",0.01000200040008,"YL",0.02000400080016,"YK",0.01000200040008,"YM",0,"YF",0.28005601120224,"YP",0,"YS",0.02000400080016,"YT",0.02000400080016,"YW",0.01000200040008,"YY",99.4698939787958,"YV",0.02000400080016,"VA",0.18,"VR",0.01,"VN",0.01,"VD",0.01,"VC",0.02,"VQ",0.01,"VE",0.02,"VG",0.05,"VH",0.01,"VI",0.33,"VL",0.15,"VK",0.01,"VM",0.04,"VF",0,"VP",0.02,"VS",0.02,"VT",0.09,"VW",0,"VY",0.01,"VV",99.01); #Generate random set of protein of defined length my $length = 1000; srand(time|$$); #array to store random proteins my @random_protein = (); #Generate reference species @random_protein = make_random_protein_set($length,1); my $count = 0; print "PAM,%identity, Sequence\n"; foreach my $eiwit (@random_protein){ $count = $count + 1; #print ">$count,".length($eiwit)."\n"; print "0,100\t$eiwit\n"; } #how many PAM do you have to simulate my $maxpam = 2500; for (my $pg=0;$pg<=$maxpam;$pg++) { my $new_protein = ""; my $dif=0; #simulate evolution my $sum; my $aa_evolution=""; my $amino; #calculate evoluted sequence for (my $aaa=0;$aaa<$length;$aaa++) { $sum = 0; $amino = substr($random_protein[$pg],$aaa,1); #print "($aaa)".substr($random_protein[$pg],$aaa,1)."\n"; my $r = rand(1)*100; my $found = 0; my $key; my %randompam; #make random array of amino acids foreach (@aa) {$randompam{$_}=int(rand(1)*1000);} my @sortedaa = sort {$randompam{$a} <=> $randompam{$b} } keys %randompam; foreach (@sortedaa) { $key = $amino.$_; $sum+=$PAM{$key}; #print "random number = $r\tsum = $sum\tKey =".$key."\tfound3 = $found3 \n"; if ($sum>=$r && $found==0) { $found=1;$aa_evolution=$_; #print "aa_evolution = $aa_evolution\n"; } } if ($amino ne $aa_evolution) { $dif++;}; $new_protein .= $aa_evolution; } $random_protein[$pg+1] = $new_protein; #print "$pg,$dif,"; print ($pg+1); print ","; #print "new protein = ".$new_protein."\n"; #calculate total difference my $tdif=0; for (my $at=0;$at<$length;$at++) { if (substr($random_protein[$pg+1],$at,1) ne substr($random_protein[0],$at,1)) {$tdif++;} } my $percent = ($length-$tdif)*100/$length; print $percent."\t$random_protein[$pg+1]\n"; #print $percent."\n"; } ################################################## #### subroutines for the random protein generation ################################################## sub make_random_protein_set { my($length,$size_of_set) = @_; my $p; my @set; for (my $i = 0; $i < $size_of_set ; ++$i) { $p = make_random_protein($length); push(@set,$p); } return @set; } sub make_random_protein { my($length) = @_; my $p; for (my $i=0 ; $i < $length ; ++$i ){ $p .= randomaminoacid(); } return $p; } sub randomaminoacid { my(@aa) = ('A','R','N','D','C','Q','E','G','H','I','L','K','M','F','P','S','T','W','Y','V'); return randomelement(@aa); } sub randomelement { my (@array) = @_; return $array[rand @array]; }