title: Molecular evolution of the primate α-/θ-defensin multigene family.
abstract: The primate α-/θ-defensin multigene family encodes versatile endogenous cationic and amphipathic peptides that have broad-spectrum antibacterial, antifungal and antiviral activity. Although previous studies have reported that α-/θ-defensin (DEFA/DEFT) genes are under birth-and-death evolution with frequent duplication and rapid evolution, the phylogenetic relationships of the primate DEFA/DEFT genes; the genetic bases for the existence of similar antimicrobial spectra among closely related species; and the evolutionary processes involved in the emergence of cyclic θ-defensins in Old World monkeys and their subsequent loss of function in humans, chimpanzees and gorillas require further investigation. In this study, the DEFA/DEFT gene repertoires from primate and treeshrew were collected, followed by detailed phylogenetic, sequence and structure, selection pressure and comparative genomics analyses. All treeshrew, prosimian and simian DEFA/DEFT genes are grouped into two major clades, which are tissue-specific for enteric and myeloid defensins in simians. The simian enteric and myeloid α-defensins are classified into six functional gene clusters with diverged sequences, variable structures, altered functional constraints and different selection pressures, which likely reflect the antimicrobial spectra among closely related species. Species-specific duplication or pseudogenization within each simian cluster implies that the antimicrobial spectrum is ever-shifting, most likely challenged by the ever-changing pathogen environment. The DEFT evolved from the myeloid DEFA8. The prosegment of θ-defensin is detected with adaptive changes coevolving with the new protein fold of mature peptide, coincident with the importance of the prosegment for the correct folding of the mature peptide. Lastly, a less-is-hitchhiking hypothesis was proposed as a possible explanation for the expansion of pseudogene DEFTP and the loss of functional DEFT, where the gain or loss of the hitchhiker is determined by its adjacent driver gene during the birth-and-death evolutionary process.
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Dong-Qiang
authors.initials: DQ
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China; Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Yaan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China; Kunming Institute of Zoology-Chinese University of Hongkong Joint Research Center for Bio-resources and Human Disease Mechanisms, Kunming, China.
authors.forename: Jing-Fei
authors.initials: JF
authors.lastname: Huang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023082:Defensins / Q000737:chemistry / Q000235:genetics*; D019143:Evolution, Molecular; D023281:Genomics; D006801:Humans; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D011323:Primates / Q000235:genetics*; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D016415:Sequence Alignment; D055672:Static Electricity; D023084:alpha-Defensins / Q000737:chemistry / Q000235:genetics*
chemical_list: D023082:Defensins; D023084:alpha-Defensins; C450142:theta-defensin