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• W1985436299 endingPage "626" @default.
• W1985436299 startingPage "616" @default.
• W1985436299 abstract "The impact of synonymous nucleotide substitutions on fitness in mammals remains controversial. Despite some indications of selective constraint, synonymous sites are often assumed to be neutral, and the rate of their evolution is used as a proxy for mutation rate. We subdivide all sites into four classes in terms of the mutable CpG context, nonCpG, postC, preG, and postCpreG, and compare four-fold synonymous sites and intron sites residing outside transposable elements. The distribution of the rate of evolution across all synonymous sites is trimodal. Rate of evolution at nonCpG synonymous sites, not preceded by C and not followed by G, is ∼10% below that at such intron sites. In contrast, rate of evolution at postCpreG synonymous sites is ∼30% above that at such intron sites. Finally, synonymous and intron postC and preG sites evolve at similar rates. The relationship between the levels of polymorphism at the corresponding synonymous and intron sites is very similar to that between their rates of evolution. Within every class, synonymous sites are occupied by G or C much more often than intron sites, whose nucleotide composition is consistent with neutral mutation–drift equilibrium. These patterns suggest that synonymous sites are under weak selection in favor of G and C, with the average coefficient s∼0.25/Ne∼10−5, where Ne is the effective population size. Such selection decelerates evolution and reduces variability at sites with symmetric mutation, but has the opposite effects at sites where the favored nucleotides are more mutable. The amino-acid composition of proteins dictates that many synonymous sites are CpGprone, which causes them, on average, to evolve faster and to be more polymorphic than intron sites. An average genotype carries ∼107 suboptimal nucleotides at synonymous sites, implying synergistic epistasis in selection against them." @default.
• W1985436299 created "2016-06-24" @default.
• W1985436299 creator A5023448826 @default.
• W1985436299 creator A5072121403 @default.
• W1985436299 creator A5077908609 @default.
• W1985436299 date "2006-06-01" @default.
• W1985436299 modified "2023-09-23" @default.
• W1985436299 title "Selection in favor of nucleotides G and C diversifies evolution rates and levels of polymorphism at mammalian synonymous sites" @default.
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• W1985436299 doi "https://doi.org/10.1016/j.jtbi.2005.10.020" @default.

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