Izumo1 and Juno: the evolutionary origins and coevolution of essential sperm–egg binding partners

Abstract

Reproductive proteins are among the most rapidly evolving classes of proteins. For a subset of these, rapid evolution is driven by positive Darwinian selection despite vital, well-conserved, reproductive functions. Izumo1 is the only essential sperm–egg fusion protein currently known on mammalian sperm, and its egg receptor (Juno; formerly Folr4) was recently discovered. Male knockout mice for Izumo1 and female knockout mice for Juno are both healthy but sterile. Here, both sperm–egg binding proteins are shown to be evolving under positive selection. Within mammals, coevolution of Izumo1 and Juno is also uncovered, suggesting that similar forces have shaped the evolutionary histories of these binding partners within Mammalia. Additionally, genomic analyses reveal an ancient origin for the Izumo gene family, initially reported as conserved exclusively in mammals. Newly identified Izumo1 orthologues could serve reproductive functions in birds, fish and reptiles. Surprisingly, these same analyses support Juno's presence in mammals alone, suggesting a recent mammalian-specific duplication and neofunctionalization of the ancestral folate receptor. Despite the indispensability of their reproductive interaction, and their apparent coevolution within Mammalia, this binding pair arose through strikingly different evolutionary forces.

BaP exposure causes oocyte meiotic arrest and fertilization failure to weaken female fertility

“…After penetration of the zona pellucida, the sperm fuses with the egg membrane to complete the spermegg interaction. Juno, a recently identified egg membrane protein, functions as a recognizer and acceptor of the sperm fusion protein Izumo-1 (69)(70)(71)(72). Mice lacking either Juno or Izumo-1 exhibit sex-specific sterility, because their gametes cannot fuse to their wild-type Figure 6.…”

The molecular mechanisms mediating mammalian fertilization

“…Additional evidence suggests that after gamete adhesion, a transmembrane region of IZUMO1 is involved in protein dimerization, which allows dimeric IZUMO1 to interact with a putative oocyte receptor (Inoue et al, 2015). To date, JUNO and IZUMO1 are the only egg receptor and sperm ligand known to interact directly to guarantee sperm-egg adhesion and this binding ability is conserved in several mammalian species (Bianchi and Wright, 2015;Grayson, 2015).…”

Epigenetic reprogramming of the zygote in mice and men: on your marks, get set, go!

“…Moreover, the sperm membrane protein IZUMO1 and its oocyte receptor JUNO have been recently identified as critical factors for mammalian sperm-oocyte interaction, fusion, fertilisation and polyspermy prevention (Bianchi & Wright 2014, Bianchi et al . 2014, Grayson 2015). Finally, the formation of the maternal and paternal pronuclei delineates the completion of mammalian fertilisation (Swain & Pool 2008).…”

“…Firstly, there is a fusion of membrane vesicle, with successive incorporation of the nuclear pore complexes into the emergent NE, followed by transportation of lamins to create the underlying nuclear lamina scaffold (Macaulay & Forbes 1996, Swain & Pool 2008). The male PN forms centrally within the human oocyte, and the female PN forms adjacent to the second polar body (Grayson 2015). Subsequently, the female PN moves towards the central location of the male PN, which increases in size as a result of oocyte-derived vesicle membrane aggregation and fusion, as well as the addition of lamin B (Swain & Pool 2008).…”