Dr. Melissa Wilson
Melissa Wilson is a computational evolutionary biologist whose main research interests include sex-biased biology and how this affects human health and disease. Atypical sex chromosome copy numbers occur frequently in humans (Turner Syndrome, individuals with a single X, occurs in 1/2500 live female births, and Klinefelter syndrome, XXY, occurs in 1/1000 males). The clinical consequences of sex chromosome copy variation is dramatically influenced by the evolutionary history of the human sex chromosomes. The Wilson lab is focusing on understanding the evolution of sex-linked gene content and how this contributes to human disease. In particular, the Wilson lab studies how to more accurately quantify variation on the sex chromosomes and how to conduct sex-stratified analyses. This work is being applied to study variation in human cancers and in the placenta. The Wilson lab also studies how patterns of variation on the sex chromosomes hold signatures of our evolutionary history as human beings, including sex-biased bottlenecks and selection that may leave some populations more vulnerable to specific diseases. The Wilson lab uses modeling and population genomics analyses of patterns of observed DNA variation to understand human demographic history.
HBES 2021 Plenary Address:
Sex-Biased Genome Evolution
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.