The molecular evolution of sperm zonadhesin.

Based on pioneering work of Hardy and Garbers, zonadhesin has become one of the best studied sperm ligands in boreoeutherian mammals, both from a biochemical and evolutionary perspective. Zonadhesin is a mosaic-type protein that localizes to the apical head of spermatozoa. In pig, cattle, rabbit and primates, zonadhesin precursor essentially consists of two or three MAM (meprin/A5 antigen/mu receptor tyrosine phosphatase) domains, one mucin-like domain, one incomplete and four complete D domains (homologous to vWFD). Mouse zonadhesin is distinguished from this general pattern by 20 extra partial D3 domains. While concerted evolution drives the divergence of the mucin-like domain in the ortholog comparison, MAM and D domains mainly diverge under the influence of drift and positive selection, both in the paralog and ortholog comparison. As can be seen particularly well within a putative binding region in the most C-terminal MAM domain, positive selection not only causes amino acid exchanges, but also promotes changes in the pattern of predicted posttranslational modification. Moving window and correlation analyses of sequence evolution and sexual body dimorphism further suggest that sexual selection, especially sperm competition, drives zonadhesin divergence. However, considering its zona pellucida avidity, female cryptic choice might as well contribute to zonadhesin evolution. Despite the general tendency for divergence of zonadhesin, conservation by negative selection dominates the evolution of most codon sites. In accordance, the distribution of EGF (epidermal growth factor)-like motifs, DP-doublets, single cysteines and CGLC motifs suggests a wide conservation of processing, folding and oligomerization of zonadhesin in pig, rabbit and primates.