title: Sequence diversity of Pan troglodytes subspecies and the impact of WFDC6 selective constraints in reproductive immunity.
abstract: Recent efforts have attempted to describe the population structure of common chimpanzee, focusing on four subspecies: Pan troglodytes verus, P. t. ellioti, P. t. troglodytes, and P. t. schweinfurthii. However, few studies have pursued the effects of natural selection in shaping their response to pathogens and reproduction. Whey acidic protein (WAP) four-disulfide core domain (WFDC) genes and neighboring semenogelin (SEMG) genes encode proteins with combined roles in immunity and fertility. They display a strikingly high rate of amino acid replacement (dN/dS), indicative of adaptive pressures during primate evolution. In human populations, three signals of selection at the WFDC locus were described, possibly influencing the proteolytic profile and antimicrobial activities of the male reproductive tract. To evaluate the patterns of genomic variation and selection at the WFDC locus in chimpanzees, we sequenced 17 WFDC genes and 47 autosomal pseudogenes in 68 chimpanzees (15 P. t. troglodytes, 22 P. t. verus, and 31 P. t. ellioti). We found a clear differentiation of P. t. verus and estimated the divergence of P. t. troglodytes and P. t. ellioti subspecies in 0.173 Myr; further, at the WFDC locus we identified a signature of strong selective constraints common to the three subspecies in WFDC6-a recent paralog of the epididymal protease inhibitor EPPIN. Overall, chimpanzees and humans do not display similar footprints of selection across the WFDC locus, possibly due to different selective pressures between the two species related to immune response and reproductive biology.
authors.affiliation: National Human Genome Research Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Zélia
authors.initials: Z
authors.lastname: Ferreira
authors.forename: Belen
authors.initials: B
authors.lastname: Hurle
authors.forename: Aida M
authors.initials: AM
authors.lastname: Andrés
authors.forename: Warren W
authors.initials: WW
authors.lastname: Kretzschmar
authors.forename: James C
authors.initials: JC
authors.lastname: Mullikin
authors.forename: Praveen F
authors.initials: PF
authors.lastname: Cherukuri
authors.forename: Pedro
authors.initials: P
authors.lastname: Cruz
authors.forename: Mary Katherine
authors.initials: MK
authors.lastname: Gonder
authors.forename: Anne C
authors.initials: AC
authors.lastname: Stone
authors.forename: Sarah
authors.initials: S
authors.lastname: Tishkoff
authors.forename: Willie J
authors.initials: WJ
authors.lastname: Swanson
authors.forename: Eric D
authors.initials: ED
authors.lastname: Green
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Clark
authors.forename: Susana
authors.initials: S
authors.lastname: Seixas
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019143:Evolution, Molecular; D014644:Genetic Variation; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D008297:Male; D002679:Pan troglodytes / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012098:Reproduction / Q000235:genetics*; D012641:Selection, Genetic; D029607:Seminal Vesicle Secretory Proteins / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: D029607:Seminal Vesicle Secretory Proteins; C424482:seminal vesicle-specific antigen
keywords: WFDC; chimpanzees; innate immunity; natural selection; reproduction; serine protease inhibitor