Immunoglobulin-Like Domains Have an Evolutionarily Conserved Role During Gamete Fusion in C. elegans and Mouse

Abstract

The spe-9 class genes are predominantly or exclusively expressed in the C. elegans male germline and play critical roles during gamete fusion. However, it is a challenge to identify mammalian orthologs that exhibit similar functions to those of the spe-9 class, since reproductive genes evolve much faster than somatic genes. In the mouse, Izumo1 gene encodes a sperm-specific transmembrane (TM) protein with the immunoglobulin (Ig)-like domain that indispensably acts during gamete fusion. The C. elegans gene spe-45 was recently identified by forward and reverse genetic approaches. It shows male germline-enriched expression and encodes an Ig-like TM protein like IZUMO1. Worms lacking spe-45 produce otherwise normal spermatozoa that are incapable of fusing with oocytes. Thus, spe-45 is a new member of the spe-9 class, and the phenotype of spe-45 mutant worms is essentially the same as that of Izumo1-knockout mice. Moreover, the Ig-like domains of SPE-45 and IZUMO1 possess similar roles to each other during gamete fusion. This indicates that C. elegans spe-45 is functionally equivalent to mouse Izumo1 and that their roles during gamete fusion have been conserved for ~1 billion years. Intriguingly, diverged organisms also have TM proteins with Ig-like domains that are involved during gamete interactions. This suggests the evolutionarily conserved roles of the Ig-like domains during fertilization, which are presumably related to associating with cis- and/or trans-partners.