Distributionofthestrengthofselectionagainstamino：选择对氨基酸的强度分布.pptVIP

Distribution of the strength of selection against amino acid replacements in human protein L.Y. Yamplosky, F.A. Kondrashov and A.S. Kondrashov Human Molecular Genetics, 2005, vol.14, no.21, 3191-3201 Background Selection (against) coefficient s =1-P(survival|substitution) Nonsense mutation Missense mutation Non-synonymous SNPs Goals Ascertain the whole distribution of coefficients of selection against amino acid replacement Characteristics of selection strength; impact of chemical properties of amino acids, reciprocal replacement Data Pathogenic missense muation (causing Mendelian Disease): Human Genetic Mutation Database Human non-synonymous SNPs: dbSNP Human-chimpanzee divergence of orthologous proteins: UCSC Methods..FMD m(1~4): mutational classes (non-CpG transversions, non-CpG transitions, CpG transversions and CpG transitions) D≈1-exp(-E), E estimated from nonsense data Methods..FMD(2) Same approach used for calculations of FSNP and FEVOL Distribution of coefficients Goals Ascertain the whole distribution of coefficients of selection against amino acid replacement Characteristics of selection strength; impact of chemical properties of amino acids, reciprocal replacement Distribution of s within across polarity classes Distribution of s of non-polar to polar reciprocal Summary Distribution of selection coefficient encompasses several orders of magnitude, thus cannot be inferred from any one kind of data Distribution of log s is, very roughly, flat: each order of magnitude is populated by 10-20% of s On average, strength of selection against a replacement is substantially higher when chemically dissimilar, but still the impact of replacement depends on its context within the protein more than on its own nature Reciprocal replacements are often associated with different selection coefficient * * ) , Pr( ) , , Pr( ) , Pr( ) , , Pr( ) , , , 1 Pr( ) , , , 1 Pr( ) , Pr( ) , , | 1 Pr( ) , , , 1 Pr( ) , | Pr( B A m B A m pathogenic B A m B A m pathogenic