Data from: Izumo1 and Juno: the evolutionary origins and coevolution of essential sperm-egg binding partners

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 conserved essential reproductive function. 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 orthologs 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.

生殖蛋白是进化速率最快的蛋白质类群之一。其中部分亚群尽管核心生殖功能高度保守，但其进化速度仍由正向达尔文选择驱动。Izumo1是目前已知的哺乳动物精子表面唯一的必需精卵融合蛋白，其卵子受体Juno（旧称Folr4）已于近期被发现。Izumo1敲除雄性小鼠与Juno敲除雌性小鼠均表现为健康但不育。本研究证实，这两种精卵结合蛋白均处于正向选择压力下发生进化。在哺乳动物类群中，Izumo1与Juno的协同进化特征也被揭示，表明相似的进化压力塑造了这对结合伴侣在哺乳纲内的进化历程。此外，基因组分析显示Izumo基因家族起源古老，此前研究认为该家族仅在哺乳动物中保守存在。本次新鉴定的Izumo1同源基因在鸟类、鱼类与爬行动物中可能具备生殖功能。令人意外的是，上述分析结果证实Juno仅存在于哺乳动物中，这表明祖先叶酸受体在近期发生了哺乳动物特异性的基因复制与新功能化事件。尽管二者的生殖互作不可或缺，且在哺乳纲内呈现明显的协同进化特征，但这对结合伴侣的起源却受到了截然不同的进化压力作用。