Abstract
BackgroundThe recent increase in human polymorphism data, together with the availability of genome sequences from several primate species, provides an unprecedented opportunity to investigate how natural selection has shaped human evolution.ResultsWe compared human branch-specific substitutions with variation data in the current human population to measure the impact of adaptive evolution on human protein coding genes. The use of single nucleotide polymorphisms (SNPs) with high derived allele frequencies (DAFs) minimized the influence of segregating slightly deleterious mutations and improved the estimation of the number of adaptive sites. Using DAF ≥ 60% we showed that the proportion of adaptive substitutions is 0.2% in the complete gene set. However, the percentage rose to 40% when we focused on genes that are specifically accelerated in the human branch with respect to the chimpanzee branch, or on genes that show signatures of adaptive selection at the codon level by the maximum likelihood based branch-site test. In general, neural genes are enriched in positive selection signatures. Genes with multiple lines of evidence of positive selection include taxilin beta, which is involved in motor nerve regeneration and syntabulin, and is required for the formation of new presynaptic boutons.ConclusionsWe combined several methods to detect adaptive evolution in human coding sequences at a genome-wide level. The use of variation data, in addition to sequence divergence information, uncovered previously undetected positive selection signatures in neural genes.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-599) contains supplementary material, which is available to authorized users.
Highlights
The recent increase in human polymorphism data, together with the availability of genome sequences from several primate species, provides an unprecedented opportunity to investigate how natural selection has shaped human evolution
For single nucleotide polymorphisms (SNPs) with derived allele frequency (DAF) ≥60%, we obtained α = 0.002, which corresponds to 0.2% adaptive substitutions
The fixation index (FI) gradually increased as we considered higher frequency SNPs, reaching a value of 1 for SNPs with derived allele frequency (DAF) ≥60% (Table 1, and Additional file 1: Tables S4 to S7)
Summary
The recent increase in human polymorphism data, together with the availability of genome sequences from several primate species, provides an unprecedented opportunity to investigate how natural selection has shaped human evolution. A powerful approach to identify positive selection in coding sequences is the comparison of substitutions and polymorphic sites using the McDonald and Kreitman (MK) test [6]. This test builds on previously developed approaches to detect deviations from neutral evolution using divergence and polymorphism data [7,8]. The MK test compares the number of non-synonymous (Dn) and synonymous (Ds) substitutions in a pair of species to the Several authors have used the MK test to estimate the importance of positive selection in diverse genomes, with contrasting results depending on the species studied [5]. Most deleterious mutations are expected to be present at low frequencies in the population; removing low frequency variants should improve the estimation of FI and other similar statistics [13,19]
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