Maggs X 

There is a current lack of consensus on the ancestral parity mode, oviparity (egg-laying) and viviparity (live-birth), of amniotes and squamates (snakes and lizards). How transitions between parity modes occur at the genomic level has primary importance on how science conceptualizes the origin of amniotes, and highly variable parity modes in Squamata. Within the context of interdisciplinary literature—medical, poultry science, reproductive biology, and evolutionary biology—I review the genomics and physiology of five broad processes (Main Five) expected to change during transitions between parity modes: eggshell formation, embryonic retention, placentation, calcium transport, and maternal-fetal immune dynamics. Throughout, I offer alternative perspectives and testable hypotheses regarding proximate causes of parity mode evolution in amniotes and squamates. Should viviparity have evolved early in the history of Lepidosaurs, I offer the basal cap hypothesis as a proximate explanation. The framework of this hypothesis can be extended to amniotes to infer their ancestral state. Medawar’s paradigm contextualizes embryos as analogous to allografts. However, an abundance of research across mammals, birds, and reptiles demonstrates that the maternal immune response to gestation/gravidity cannot be explained by immunosuppression, inertness, evasion, or immunological barriers. However, a rare example of a species with an apparently inert response to oviparous gravidity is Lampropholis guichenoti, an oviparous skink that differentially expresses zero genes during gravidity—making it a reasonable model for the original amniote egg. Overall, this review grounds itself in the historical literature while offering a modern perspective on a subject that has fascinated scientists for centuries—the origin of amniotes. Based on the cumulative evidence across the Main Five, I provide a mechanism through which squamates may reverse back to oviparity; and make predictions on the directionality of transitions in three reproductively bimodal species. I encourage the scientific community to utilize this manuscript as a resource in comparative genomics studies, embrace the complexity of the system, and thoughtfully consider the framework proposed.