Significance of Population Size on the Fixation of Nonsynonymous Mutations in Genes Under Varying Levels of Selection Pressure

摘要

Previous studies observed a higher ratio of divergences at nonsynonymous and synonymous sites (omega = d(N)/d(S)) in species with a small population size compared to that estimated for those with a large population size. Here we examined the theoretical relationship between v, effective population size (N-e), and selection coefficient (s). Our analysis revealed that when purifying selection is high, omega of species with small N-e is much higher than that of species with large N-e. However the difference between the two omega reduces with the decline in selection pressure (s -> 0). We examined this relationship using primate and rodent genes and found that the v estimated for highly constrained genes of primates was up to 2.9 times higher than that obtained for their orthologous rodent genes. Conversely, for genes under weak purifying selection the omega of primates was only 17% higher than that of rodents. When tissue specificity was used as a proxy for selection pressure we found that the omega of broadly expressed genes of primates was up to 2.1-fold higher than that of their rodent counterparts and this difference was only 27% for tissue specific genes. Since most of the nonsynonymous mutations in constrained or broadly expressed genes are deleterious, fixation of these mutations is influenced by N-e. This results in a higher omega of these genes in primates compared to those from rodents. Conversely, the majority of nonsynonymous mutations in less-constrained or tissue-specific genes are neutral or nearly neutral and therefore fixation of them is largely independent of N-e, which leads to the similarity of omega in primates and rodents.