The molecular evolution of acrosin in placental mammals.
Acrosin is thought to fulfill several different roles in fertilization including that of a serine protease and in secondary zona pellucida (ZP) binding. However, acrosin's importance as a fertilization protein has been questioned. Especially since it was discovered that acrosin knockout mice are fertile. In this study, we explored the sites involved in serine protease activity and secondary binding. We also assessed conservation in functional sites across species and examined whether amino acid changes present in the human population have the potential to affect fertility. In addition, since many mammalian reproduction proteins have been found to evolve rapidly, we tested for positive selection. Sequences from 43 mammals from all 19 placental orders, which included a total of 828 nucleotides from acrosin exons 2, 3, 4, and a portion of exon 5, were obtained. We found that all sites of the serine catalytic triad as well as three other sites linked to catalytic activity were completely conserved. Five of six sites proposed to play a role in secondary binding were 100% conserved as basic residues. These results support an evolutionary conserved role for acrosin as a serine protease and secondary binding protein across placental mammals. We found statistically significant support for positive selection within acrosin, but no single amino acid site reached the significance level of P > 0.95 for inclusion within the category omega > 1. Based upon two amino acid mutation scoring systems, three out of seven human residue changing single nucleotide polymorphisms (SNPs) were found to be potentially protein-altering mutations.
Raterman
Denise
D
Department of Biology, University of California-Riverside, Riverside, California 92521, USA. gansed01@student.ucr.edu
Springer
Mark S
MS
D000176:Acrosin / Q000235:genetics*; D000818:Animals; D002417:Cattle; D019143:Evolution, Molecular; D005260:Female; D005306:Fertilization; D006801:Humans; D008297:Male; D008322:Mammals; D051379:Mice; D002679:Pan troglodytes; D010920:Placenta / Q000502:physiology*; D011247:Pregnancy; D013094:Spermatozoa / Q000502:physiology; D015044:Zona Pellucida
D000176:Acrosin