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 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.

生殖蛋白是进化速率最快的蛋白质类别之一。其中部分亚型尽管具备至关重要且高度保守的生殖功能，但其快速演化却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必需的精卵融合蛋白，其卵子受体Juno（旧称Folr4）已于近期被成功鉴定。Izumo1雄性敲除小鼠与Juno雌性敲除小鼠均表现为健康但不育的表型。本研究证实，这两种精卵结合蛋白均处于正向达尔文选择的进化压力之下。在哺乳纲类群中，研究还揭示了Izumo1与Juno的协同进化现象，表明相似的进化力量塑造了这对结合伴侣在哺乳纲中的演化历程。此外，基因组分析显示Izumo基因家族起源古老，此前的研究认为该家族仅保守存在于哺乳动物中。本次研究新鉴定出的Izumo1直系同源物，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，同类分析结果仅支持Juno存在于哺乳动物中，这表明祖先叶酸受体发生了一次哺乳纲特异性的近期复制事件，并产生了新功能（neofunctionalization）。尽管二者的生殖互作不可或缺，且在哺乳纲中呈现明显的协同进化，但这一结合蛋白对的演化驱动力却存在显著差异。