title: Recent coselection in human populations revealed by protein-protein interaction network.
abstract: Genome-wide scans for signals of natural selection in human populations have identified a large number of candidate loci that underlie local adaptations. This is surprising given the relatively short evolutionary time since the divergence of the human population. One hypothesis that has not been formally examined is whether and how the recent human evolution may have been shaped by coselection in the context of complex molecular interactome. In this study, genome-wide signals of selection were scanned in East Asians, Europeans, and Africans using 1000 Genome data, and subsequently mapped onto the protein-protein interaction (PPI) network. We found that the candidate genes of recent positive selection localized significantly closer to each other on the PPI network than expected, revealing substantial clustering of selected genes. Furthermore, gene pairs of shorter PPI network distances showed higher similarities of their recent evolutionary paths than those further apart. Last, subnetworks enriched with recent coselection signals were identified, which are substantially overrepresented in biological pathways related to signal transduction, neurogenesis, and immune function. These results provide the first genome-wide evidence for association of recent selection signals with the PPI network, shedding light on the potential mechanisms of recent coselection in the human genome.
authors.affiliation: Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Qian
authors.affiliation: Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China tangkun@picb.ac.cn.
authors.forename: Kun
authors.initials: K
authors.lastname: Tang
mesh_terms: D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D019143:Evolution, Molecular; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D006239:Haplotypes; D016045:Human Genome Project; D006801:Humans; D007107:Immune System; D055495:Neurogenesis; D020641:Polymorphism, Single Nucleotide; D060066:Protein Interaction Maps / Q000235:genetics*; D012641:Selection, Genetic / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D044465:White People / Q000235:genetics
keywords: PPI network; coevolution; coselection; network topology; pathway selection; recent positive selection