title: Natural selection has driven population differentiation in modern humans.
abstract: The considerable range of observed phenotypic variation in human populations may reflect, in part, distinctive processes of natural selection and adaptation to variable environmental conditions. Although recent genome-wide studies have identified candidate regions under selection, it is not yet clear how natural selection has shaped population differentiation. Here, we have analyzed the degree of population differentiation at 2.8 million Phase II HapMap single-nucleotide polymorphisms. We find that negative selection has globally reduced population differentiation at amino acid-altering mutations, particularly in disease-related genes. Conversely, positive selection has ensured the regional adaptation of human populations by increasing population differentiation in gene regions, primarily at nonsynonymous and 5'-UTR variants. Our analyses identify a fraction of loci that have contributed, and probably still contribute, to the morphological and disease-related phenotypic diversity of current human populations.
authors.affiliation: Human Evolutionary Genetics Unit, Centre National de la Recherche Scientifique-Unité de Recherche Associée (CNRS-URA3012), Institut Pasteur, 25 rue Dr. Roux, Paris 75015, France.
authors.forename: Luis B
authors.initials: LB
authors.lastname: Barreiro
authors.forename: Guillaume
authors.initials: G
authors.lastname: Laval
authors.forename: Hélène
authors.initials: H
authors.lastname: Quach
authors.forename: Etienne
authors.initials: E
authors.lastname: Patin
authors.forename: Lluís
authors.initials: L
authors.lastname: Quintana-Murci
mesh_terms: D005796:Genes; D005828:Genetics, Population; D015894:Genome, Human; D006239:Haplotypes; D006801:Humans; D008962:Models, Theoretical; D020641:Polymorphism, Single Nucleotide; D044382:Population Groups / Q000235:genetics*; D012641:Selection, Genetic; D020506:Untranslated Regions / Q000235:genetics
chemical_list: D020506:Untranslated Regions