简介：Theratioofnonsynonymoussubstitutionrate(Ka)tosynonymoussubstitutionrate(Ks)iswidelyusedasanindicatorofselectivepressureatsequencelevelamongdifferentspecies,anddiversemutationmodelshavebeenincorporatedintoseveralcomputingmethods.Wehavepreviouslydevelopedanewγ-MYNmethodbycapturingakeydynamicevolutiontraitofDNAnucleotidesequences,inconsiderationofvaryingmutationratesacrosssites.WenowreportafurtherimprovementofNG,LWL,MLWL,LPB,MLPB,andYNmethodsbasedonanintroductionofgammadistributiontoillustratethevariationofrawmutationrateoversites.Thenoveltycomesintwoways:(1)weincorporateanoptimalgammadistributionshapeparameteraintoγ-NG,γ-LWL,γ-MLWL,γ-LPB,γ-MLPB,andγ-YNmethods;(2)weinvestigatehowvariablesubstitutionratesaffectthemethodsthatadoptdifferentmodelsaswellastheinterplayamongfourevolutionalfeatureswithrespecttoKa/Kscomputations.Ourresultssuggestthatvariablesubstitutionratesoversitesundernegativeselectionexhibitanoppositeeffectonωestimatescomparedwiththoseunderpositiveselection.WebelievethatthesensitivityofournewmethodshasbeenimprovedthanthatoftheiroriginalmethodsunderdiverseconditionsanditisadvantageoustointroducenovelparametersforKa/Kscomputation.