Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico.
Department of Biochemistry, Genetics and Immunology, School of Biology, University of Vigo, Vigo, Spain.
J Mol Evol. 2018 Dec;86(9):635-645. doi: 10.1007/s00239-018-9872-6. Epub 2018 Oct 28.
Cysteine-RIch Secretory Proteins (CRISPs) constitute a versatile family, with functions in reptilian venom and mammalian reproduction. Mammals generally express three CRISPs, four in mice, and all are highly expressed in male reproductive tissues, either testis or accessory organs. Because reproductive proteins often evolve adaptively in response to post-copulatory sexual selection, we hypothesized that mammalian CRISPs, with important roles in male reproduction, could have undergone positive selection promoting their divergence. We explored the molecular adaptation of mammalian CRISPs applying phylogenetic methods. Our analyses revealed the evidence of positive selection in all mammalian CRISPs. The intensity of positive selection was heterogeneous among CRISP members, being stronger in CRISP3 than in CRISP1 and CRISP2, and also across functional domains, having stronger impact on Pathogenesis-Related 1 (PR-1) in CRISP2 and on Ion Channel Regulator (ICR) in CRISP1 and CRISP3. In addition, we discovered a new CRISP in some rodent species, suggesting that the acquisition of new CRISP components could contribute to male reproductive success or to acquire new physiological roles. Signatures of positive selection were not focused on any particular mammalian group, suggesting that adaptive evolution is a recurrent pattern in mammalian CRISPs. Our findings support a model of CRISP family diversification driven by episodes of duplication and posterior neofunctionalization, and provide potential adaptive changes responsible for interspecific differences in CRISPs activity.
半胱氨酸丰富分泌蛋白（CRISPs）构成了一个多功能家族，在爬行动物毒液和哺乳动物生殖中具有功能。哺乳动物通常表达三种 CRISPs，在老鼠中则表达四种，所有这些蛋白在雄性生殖组织中高度表达，无论是睾丸还是附属器官。由于生殖蛋白经常在适应交配后性选择方面进化，因此我们假设在雄性生殖中具有重要作用的哺乳动物 CRISPs 可能经历了正选择，促进了它们的分化。我们应用系统发育方法探索了哺乳动物 CRISPs 的分子适应。我们的分析表明，所有哺乳动物 CRISPs 都存在正选择的证据。CRISP 成员之间的正选择强度存在异质性，CRISP3 比 CRISP1 和 CRISP2 更强，并且在功能域之间也存在差异，在 CRISP2 中对病原体相关蛋白 1（PR-1）和在 CRISP1 和 CRISP3 中对离子通道调节剂（ICR）的影响更强。此外，我们在一些啮齿动物物种中发现了一种新的 CRISP，表明获得新的 CRISP 成分可能有助于雄性生殖成功或获得新的生理功能。正选择的特征并没有集中在任何特定的哺乳动物群体上，这表明适应性进化是哺乳动物 CRISPs 的一种反复出现的模式。我们的研究结果支持了由重复和新功能化事件驱动的 CRISP 家族多样化模型，并提供了导致 CRISPs 活性种间差异的潜在适应性变化。
