Positive Selection in the Evolution of Mammalian CRISPs
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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.
KeywordsMammalian CRISP Reproduction Positive selection Ion channel Fertility
The authors would like to thank Jose Luis De la Vega, Paulina Torres, Francisco Herrera, and Shirley Ainsworth for technical assistance; Juan Manuel Hurtado, Roberto Rodríguez, David Santiago Castañeda, Omar Arriaga, and Arturo Ocádiz for computing services; and Miguel Arenas for the critical revision of this manuscript. Computational analyses were supported by the cluster of the Instituto de Biotecnología UNAM (http://teopanzolco.ibt.unam.mx//).
This work was supported by Dirección General de Asuntos de Personal Académico/Universidad Nacional Autónoma de México (DGAPA/UNAM) (Contract Grant Number IN203116 to C.T. and postdoctoral fellowship to A.V.), the Alexander von Humboldt Foundation (w/o Grant Number to C.T.), and Juan de la Cierva postdoctoral fellowship (IJCI-2016-29550) from Spanish Government to A.V.
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Conflict of interest
The authors declare that they have no competing interests.
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