title: A scan for human-specific relaxation of negative selection reveals unexpected polymorphism in proteasome genes.
abstract: Environmental or genomic changes during evolution can relax negative selection pressure on specific loci, permitting high frequency polymorphisms at previously conserved sites. Here, we jointly analyze population genomic and comparative genomic data to search for functional processes showing relaxed negative selection specifically in the human lineage, whereas remaining evolutionarily conserved in other mammals. Consistent with previous studies, we find that olfactory receptor genes display such a signature of relaxation in humans. Intriguingly, proteasome genes also show a prominent signal of human-specific relaxation: multiple proteasome subunits, including four members of the catalytic core particle, contain high frequency nonsynonymous polymorphisms at sites conserved across mammals. Chimpanzee proteasome genes do not display a similar trend. Human proteasome genes also bear no evidence of recent positive or balancing selection. These results suggest human-specific relaxation of negative selection in proteasome subunits; the exact biological causes, however, remain unknown.
authors.affiliation: Department of Integrative Biology, University of California, Berkeley, CA, USA. somel.mehmet@gmail.com
authors.forename: Mehmet
authors.initials: M
authors.lastname: Somel
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Wilson Sayres
authors.forename: Gregory
authors.initials: G
authors.lastname: Jordan
authors.forename: Emilia
authors.initials: E
authors.lastname: Huerta-Sanchez
authors.forename: Matteo
authors.initials: M
authors.lastname: Fumagalli
authors.forename: Anna
authors.initials: A
authors.lastname: Ferrer-Admetlla
authors.forename: Rasmus
authors.initials: R
authors.lastname: Nielsen
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D005787:Gene Frequency; D015894:Genome, Human; D006801:Humans; D002679:Pan troglodytes; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D046988:Proteasome Endopeptidase Complex / Q000235:genetics*; D012641:Selection, Genetic
chemical_list: D046988:Proteasome Endopeptidase Complex
keywords: human evolution; negative selection; olfactory transduction; proteasome; relaxation of constraints