Journal Article

Purifying selection shapes the coincident SNP distribution of primate coding sequences

Hung, Li-Yuan, Chuang, Trees-Juen, Chen, Chia-Ying, Wu, Chan-Shuo

2016

Overview

Genome-wide analysis has observed an excess of coincident single nucleotide polymorphisms (coSNPs) at human-chimpanzee orthologous positions and suggested that this is due to cryptic variation in the mutation rate. While this phenomenon primarily corresponds with non-coding coSNPs, the situation in coding sequences remains unclear. Here we calculate the observed-to-expected ratio of coSNPs (coSNP O/E ) to estimate the prevalence of human-chimpanzee coSNPs and show that the excess of coSNPs is also present in coding regions. Intriguingly, coSNP O/E is much higher at zero-fold than at nonzero-fold degenerate sites; such a difference is due to an elevation of coSNP O/E at zero-fold degenerate sites, rather than a reduction at nonzero-fold degenerate ones. These trends are independent of chimpanzee subpopulation, population size, or sequencing techniques; and hold in broad generality across primates. We find that this discrepancy cannot fully explained by sequence contexts, shared ancestral polymorphisms, SNP density and recombination rate and that coSNP O/E in coding sequences is significantly influenced by purifying selection. We also show that selection and mutation rate affect coSNP O/E independently and coSNPs tend to be less damaging and more correlated with human diseases than non-coSNPs. These suggest that coSNPs may represent a “signature” during primate protein evolution.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 45/23 / 45/43 / 631/114/2785 / 631/181/2474 / Animals / Databases, Genetic / Evolution, Molecular / Humanities and Social Sciences / Humans / multidisciplinary / Mutation Rate / Pan troglodytes - genetics / Polymorphism, Single Nucleotide / Science / Selection, Genetic / Sequence Analysis, DNA - methods