Human and Non-Human Primate Genomes Share Hotspots of Positive Selection

Abstract

Among primates, genome-wide analysis of recent positive selection is currently limited to the human species because it requires extensive sampling of genotypic data from many individuals. The extent to which genes positively selected in human also present adaptive changes in other primates therefore remains unknown. This question is important because a gene that has been positively selected independently in the human and in other primate lineages may be less likely to be involved in human specific phenotypic changes such as dietary habits or cognitive abilities. To answer this question, we analysed heterozygous Single Nucleotide Polymorphisms (SNPs) in the genomes of single human, chimpanzee, orangutan, and macaque individuals using a new method aiming to identify selective sweeps genome-wide. We found an unexpectedly high number of orthologous genes exhibiting signatures of a selective sweep simultaneously in several primate species, suggesting the presence of hotspots of positive selection. A similar significant excess is evident when comparing genes positively selected during recent human evolution with genes subjected to positive selection in their coding sequence in other primate lineages and identified using a different test. These findings are further supported by comparing several published human genome scans for positive selection with our findings in non-human primate genomes. We thus provide extensive evidence that the co-occurrence of positive selection in humans and in other primates at the same genetic loci can be measured with only four species, an indication that it may be a widespread phenomenon. The identification of positive selection in humans alongside other primates is a powerful tool to outline those genes that were selected uniquely during recent human evolution. An advantageous mutation spreads from generation to generation in a population until individuals that carry it, because of their higher reproductive success, completely replace those that do not. This process, commonly known as positive Darwinian selection, requires the selected mutation to induce a new non-neutral heritable phenotypic trait, and this has been shown to occur unexpectedly frequently during recent human evolution. Although the exact advantageous mutation is difficult to identify, it leaves a wider footprint on neighbouring linked neutral variation called a selective sweep. We have developed an empirical method that uses whole-genome shotgun sequences of single individuals to detect selective sweeps. By doing so, we were able to extend to chimpanzee, orangutan, and macaque individuals analyses of recent positive selection that until now were only available for human. Comparisons of genes candidates for positive selection between human and non-human primates then revealed an unexpectedly high number of cases where a selective sweep at a gene in humans is mirrored by independent positive selection at the same gene in multiple other primates. This result has future implications for understanding the nature of biological changes that underlie selective sweeps in humans.