Molecular population genetics of the gene encoding the human fertilization protein zonadhesin reveals rapid adaptive evolution.
A hallmark of positive selection (adaptive evolution) in protein-coding regions is a d(N)/d(S) ratio >1, where d(N) is the number of nonsynonymous substitutions/nonsynonymous sites and d(S) is the number of synonymous substitutions/synonymous sites. Zonadhesin is a male reproductive protein localized on the sperm head, comprising many domains known to be involved in cell-cell interaction or cell adhesion. Previous studies have shown that VWD domains (homologous to the D domains of the von Willebrand factor) are involved directly in binding to the female zona pellucida (ZP) in a species-specific manner. In this study, we sequenced 47 coding exons in 12 primate species and, by using maximum-likelihood methods to determine sites under positive selection, we show that VWD2, membrane/A5 antigen mu receptor, and mucin-like domains in zonadhesin are rapidly evolving and, thus, may be involved in binding to the ZP in a species-specific manner in primates. In addition, polymorphism data from 48 human individuals revealed significant polymorphism-to-divergence heterogeneity and a significant departure from equilibrium-neutral expectations in the frequency spectrum, suggesting balancing selection and positive selection occurring in zonadhesin (ZAN) within human populations. Finally, we observe adaptive evolution in haplotypes segregating for a frameshift mutation that was previously thought to indicate that ZAN was a potential pseudogene.
Gasper
Joe
J
Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Swanson
Willie J
WJ
D000818:Animals; D019143:Evolution, Molecular; D005091:Exons; D005260:Female; D005828:Genetics, Population; D006801:Humans; D007438:Introns; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D010802:Phylogeny; D011110:Polymorphism, Genetic; D011323:Primates / Q000235:genetics; D017434:Protein Structure, Tertiary; D012641:Selection, Genetic; D013045:Species Specificity; D013094:Spermatozoa / Q000737:chemistry / Q000502:physiology
D008565:Membrane Proteins; C096806:zonadhesin