title: Evidence of convergent evolution in humans and macaques supports an adaptive role for copy number variation of the β-defensin-2 gene.
abstract: β-defensins are a family of important peptides of innate immunity, involved in host defense, immunomodulation, reproduction, and pigmentation. Genes encoding β-defensins show evidence of birth-and-death evolution, adaptation by amino acid sequence changes, and extensive copy number variation (CNV) within humans and other species. The role of CNV in the adaptation of β-defensins to new functions remains unclear, as does the adaptive role of CNV in general. Here, we fine-map CNV of a cluster of β-defensins in humans and rhesus macaques. Remarkably, we found that the structure of the CNV is different between primates, with distinct mutational origins and CNV boundaries defined by retroviral long terminal repeat elements. Although the human β-defensin CNV region is 322 kb and encompasses several genes, including β-defensins, a long noncoding RNA gene, and testes-specific zinc-finger transcription factors, the orthologous region in the rhesus macaque shows CNV of a 20-kb region, containing only a single gene, the ortholog of the human β-defensin-2 gene. Despite its independent origins, the range of gene copy numbers in the rhesus macaque is similar to humans. In addition, the rhesus macaque gene has been subject to divergent positive selection at the amino acid level following its initial duplication event between 3 and 9.5 Ma, suggesting adaptation of this gene as the macaque successfully colonized novel environments outside Africa. Therefore, the molecular phenotype of β-defensin-2 CNV has undergone convergent evolution, and this gene shows evidence of adaptation at the amino acid level in rhesus macaques.
authors.affiliation: Department of Genetics, University of Leicester, United Kingdom.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ottolini
authors.affiliation: Department of Microbiology and Immunology, University of California Davis School of Medicine.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hornsby
authors.affiliation: Department of Genetics, University of Leicester, United Kingdom.
authors.forename: Razan
authors.initials: R
authors.lastname: Abujaber
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California San Francisco Present address: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Jacqueline A L
authors.initials: JA
authors.lastname: MacArthur
authors.affiliation: Department of Genetics, University of Leicester, United Kingdom.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Badge
authors.affiliation: Department of Biology, University of Leicester, United Kingdom.
authors.forename: Trude
authors.initials: T
authors.lastname: Schwarzacher
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California San Francisco Present address: Bluestone Center for Clinical Research, New York University College of Dentistry, New York, New York.
authors.forename: Donna G
authors.initials: DG
authors.lastname: Albertson
authors.affiliation: Department of Microbiology and Immunology, University of California Davis School of Medicine.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Bevins
authors.affiliation: Department of Microbiology and Immunology, University of California Davis School of Medicine Department of Medicine, Center for Comparative Medicine, and the California National Primate Research Center, University of California.
authors.forename: Jay V
authors.initials: JV
authors.lastname: Solnick
authors.affiliation: Department of Genetics, University of Leicester, United Kingdom ejh33@le.ac.uk.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Hollox
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000818:Animals; D056915:DNA Copy Number Variations; D019143:Evolution, Molecular; D006801:Humans; D008253:Macaca mulatta; D009154:Mutation; D012641:Selection, Genetic; D023083:beta-Defensins / Q000235:genetics*
chemical_list: D023083:beta-Defensins
keywords: copy number variation; defensin; evolution; genome structure; macaque