Revisiting the evolutionary analysis of mammalian CRISPs reveals positive selection

Abstract

Cysteine-rich secretory proteins (CRISPs) constitute a versatile family, with functions that include being components of reptilian venom and participation in mammalian reproduction. While non-mammalian vertebrates express a single CRISP gene, mammals generally express three CRISP paralogs. A previous study assessing the molecular evolution of vertebrate CRISPs revealed strong positive selection in reptilian CRISP and negative selection in mammalian CRISPs. In this study, we re-assessed molecular adaptation of mammalian CRISPs through an analysis of larger sequence datasets that represent mammalian diversity. Our analyses show evidence of recent episodes of positive selection for all mammalian CRISPs. Intensity of positive selection was heterogeneous both among CRISP paralogs (being stronger in CRISP3 than in CRISP1 and CRISP2) and across functional domains (having more impact on CRD or PR-1 domain). Analysis of episodic selection did not yield strong signatures of adaptive evolution in any particular mammalian group, suggesting that positive selection was more pervasive on mammalian CRISPs. Our findings provide evidence of adaptive evolution in a family of reproduction-related proteins, and offer interesting insights regarding the role of mammalian CRISPs in fertility and speciation.