title: The evolution of lineage-specific clusters of single nucleotide substitutions in the human genome.
abstract: Genomic regions harboring large numbers of human-specific single nucleotide substitutions are of significant interest since they are potential genomic foci underlying the evolution of human-specific traits as well as human adaptive evolution. Previous studies aimed to identify such regions either used pre-defined genomic locations such as coding sequences and conserved genomic elements or employed sliding window methods. Such approaches may miss clusters of substitutions occurring in regions other than those pre-defined locations, or not be able to distinguish human-specific clusters of substitutions from regions of generally high substitution rates. Here, we conduct a 'maximal segment' analysis to scan the whole human genome to identify clusters of human-specific substitutions that occurred since the divergence of the human and the chimpanzee genomes. This method can identify species-specific clusters of substitutions while not relying on pre-defined regions. We thus identify thousands of clusters of human-specific single nucleotide substitutions. The evolution of such clusters is driven by a combination of several different evolutionary processes including increased regional mutation rate, recombination-associated processes, and positive selection. These newly identified regions of human-specific substitution clusters include large numbers of previously identified human accelerated regions, and exhibit significant enrichments of genes involved in several developmental processes. Our study provides a useful tool to study the evolution of the human genome.
authors.affiliation: School of Biology, Georgia Institute of Technology, 310 Ferst Drive, Atlanta, GA 30332, USA. kexu@gatech.edu
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.forename: Jianrong
authors.initials: J
authors.lastname: Wang
authors.forename: Navin
authors.initials: N
authors.lastname: Elango
authors.forename: Soojin V
authors.initials: SV
authors.lastname: Yi
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics; D000483:Alleles; D000818:Animals; D002874:Chromosome Mapping; D019143:Evolution, Molecular; D015894:Genome, Human; D006801:Humans; D008957:Models, Genetic; D005810:Multigene Family; D059645:Mutation Rate; D002679:Pan troglodytes / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011995:Recombination, Genetic; D012641:Selection, Genetic
keywords: Biased gene conversion; Derived allele frequency; Human-specific single nucleotide substitutions; Maximal segments; Positive selection