Rapid divergence of a gamete recognition gene promoted macroevolution of Eutheria

Abstract

Background Speciation genes contribute disproportionately to species divergence, but few examples exist, especially in vertebrates. Here we test whether Zan, which encodes the sperm acrosomal protein zonadhesin that mediates species-specific adhesion to the egg’s zona pellucida, is a speciation gene in placental mammals. Results Genomic ontogeny reveals that Zan arose by repurposing of a stem vertebrate gene that was lost in multiple lineages but retained in Eutheria on acquiring a function in egg recognition. A 112-species Zan sequence phylogeny, representing 17 of 19 placental Orders, resolves all species into monophyletic groups corresponding to recognized Orders and Suborders, with <5% unsupported nodes. Three other rapidly evolving germ cell genes (Adam2, Zp2, and Prm1), a paralogous somatic cell gene (TectA), and a mitochondrial gene commonly used for phylogenetic analyses (Cytb) all yield trees with poorer resolution than the Zan tree and inferior topologies relative to a widely accepted mammalian supertree. Zan divergence by intense positive selection produces dramatic species differences in the protein’s properties, with ordinal divergence rates generally reflecting species richness of placental Orders consistent with expectations for a speciation gene that acts across a wide range of taxa. Furthermore, Zan’s combined phylogenetic utility and divergence exceeds those of all other genes known to have evolved in Eutheria by positive selection, including the only other mammalian speciation gene, Prdm9. Conclusions Species-specific egg recognition conferred by Zan’s functional divergence served as a mode of prezygotic reproductive isolation that promoted the extraordinary adaptive radiation and success of Eutheria.

SMA20/PMIS2 Is a Rapidly Evolving Sperm Membrane Alloantigen with Possible Species-Divergent Function in Fertilization

“…In contrast, a comparable word search retrieved annotated Atp4a, Haus5, and Gapdhs from 373, 376, and 294 placental genomes, respectively. Pairwise interrogation of the Atp4a-Haus5 intergenic region with the pig SMA20 cDNA sequence correctly identified the two-exon Pmis2 gene in five representative species (Figure 6), including the previously un-annotated pig locus, as well as Pmis2 from armadillo (Dasypus novemcitus), a relatively primitive species from superorder Xenarthra that diverged from the other species near the base of the placental phylogeny [28,29]. To determine if Pmis2 is conserved in Placentalia, we interrogated, via a pairwise comparison to the armadillo Pmis2 cds, the Atp4a-Haus5 intergenic sequences in the genomes of 20 randomly chosen placental species in which Pmis2 had previously evaded annotation, and we identified the two-exon Pmis2 gene in all 20 species.…”

“…Species variation in fertilization events necessarily require corresponding species differences in the nature or timing of molecular processes that mediate them. Rapid molecular evolution is a common feature of reproductive proteins in general [53] and of fertilization proteins in particular [29,52], with the adaptive divergence of any one protein potentially driving co-evolutionary divergence of its interacting partners [54]. Known sources of species variation in gene products include protein domain and wholegene duplications [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][53][54][55], rapid sequence divergence by positive selection [29,53,54], concerted evolution by gene conversion [53][54][55], and individual variation in pre-mRNA splicing [56].…”

“…Rapid molecular evolution is a common feature of reproductive proteins in general [53] and of fertilization proteins in particular [29,52], with the adaptive divergence of any one protein potentially driving co-evolutionary divergence of its interacting partners [54]. Known sources of species variation in gene products include protein domain and wholegene duplications [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][53][54][55], rapid sequence divergence by positive selection [29,53,54], concerted evolution by gene conversion [53][54][55], and individual variation in pre-mRNA splicing [56]. Our genome ontogeny results showing that Sma20/Pmis2 arose de novo in the lineage leading to extant placental mammals add this relatively rare mode of new gene formation [57,58] to the repertoire of genetic processes that drive the species diversification of fertilization proteins and cellular events.…”

Gamete Recognition Gene Divergence Yields a Robust Eutherian Phylogeny across Taxonomic Levels

“…Accordingly, the divergence of a "speciation gene" may accurately represent species phylogeny because its evolution does not simply serve as a clock, but instead reflects the gene's direct contribution to speciation [58][59][60]. We previously found that Zan is a speciation gene in placental mammals, and its divergence tracks the evolutionary history of Eutheria [61]. Zan encodes the sperm protein zonadhesin, which mediates species-specific recognition of the egg, and rapid Zan evolution by intense positive selection promotes prezygotic reproductive isolation [62][63][64][65][66].…”

“…Zan encodes the sperm protein zonadhesin, which mediates species-specific recognition of the egg, and rapid Zan evolution by intense positive selection promotes prezygotic reproductive isolation [62][63][64][65][66]. Despite being a single character evolving under positive selection, the Zan tree was generally congruent to a eutherian supertree [28,61] but did exhibit significant incongruencies in part, and presumably, because it was more highly resolved [61].…”