I will present research and theory connecting the intersecting evolution of sex chromosomes, the placenta, and pregnancy, and how those combine to result in sex differences in many human diseases

Sex-biased genome evolution. Melissa Wilson. Human Behavior & Evolution Society HBES 2021, Jun-Jul 2021. https://www.hbes.com/hbes-2021-wilson/

Abstract: I will present research and theory connecting the intersecting evolution of sex chromosomes, the placenta, and pregnancy, and how those combine to result in sex differences in many human diseases . I will propose how changes in industrialized society (e.g., having fewer pregnancies, and potentially even that the age at first reproduction is later) may be exacerbating these sex differences. In particular, we hypothesize that, ancestrally, sex-specific immune modulation evolved to facilitate survival of the pregnant person in the presence of an invasive placenta and an immunologically challenging pregnancy – an idea we term the ‘pregnancy compensation hypothesis’ (PCH). Further, we propose that sex differences in immune function are mediated, at least in part, by the evolution of gene content and dosage on the sex chromosomes, and are regulated by reproductive hormones. Finally, we propose that changes in reproductive ecology in industrialized environments exacerbate these evolved sex differences, resulting in the increasing risk of autoimmune disease observed in females, and a counteracting reduction in diseases such as cancer that can be combated by heightened immune surveillance. The PCH generates a series of expectations that can be tested empirically and that may help to identify the mechanisms underlying sex differences in modern human diseases. I will also discuss how the potentially confounding observations of male-biased disease severity and death due to COVID-19, and the female-bias of severe response to the SARS-CoV2 vaccines are consistent with the PCH.