Why are human bodies vulnerable to disease? Evolutionary medicine approaches this question through principles that clinical research alone does not capture — genetic conflict between parent and offspring, trade-offs between competing fitness demands, mismatches between the environment our genomes evolved in and the one we now inhabit, and the legacy of natural selection acting differently across populations. We apply these principles to two areas: the placenta, where maternal-fetal conflict has driven rapid evolution with consequences for pregnancy and cancer, and the human genome, where the imprint of selection and demographic history explains population differences in disease risk.

The placenta is one of the most rapidly evolving organs in mammals. W. D. Hamilton's theory of inclusive fitness and Robert Trivers's theory of parent–offspring conflict explain why: the fetal genome is selected to extract more resources from the mother than is in her own reproductive interest, while the maternal genome is selected to resist. The placenta is the battleground where this conflict plays out, and the result is an evolutionary arms race that has driven extraordinary diversity in placental structure — from the deeply invasive hemochorial placenta of humans, where fetal cells breach the uterine wall and remodel maternal blood vessels, to the non-invasive epitheliochorial placenta of cows and pigs, where maternal and fetal tissues barely touch.

This diversity offers a natural experiment for understanding how the maternal-fetal interaction has evolved and how it affects health and disease on both sides. By comparing gene regulation across placental types, we can ask how evolution has repeatedly tuned the balance between fetal demand and maternal control, and what happens when that balance breaks down. Pregnancy disorders such as preeclampsia and gestational diabetes arise when the regulatory balance between fetal demand and maternal control breaks down, a direct consequence of the conflict that drives placental evolution in the first place. At the same time, the regulatory programs underlying placental function share deep signatures with those co-opted by cancer — both involve tissue remodelling, immune modulation and angiogenesis — raising the possibility that placental evolution has shaped cancer vulnerability in ways that differ across mammalian lineages. We are using single-cell transcriptomics and cross-species comparisons to map how the maternal-fetal regulatory dialogue has been rewired across mammals, with the aim of tracing how evolutionary changes in this dialogue predispose to disease.

The human genome carries a record of every selective pressure, demographic event and mutational process in our evolutionary history. With complete, haplotype-resolved genome assemblies now available at population scale, we can begin to read that record at the resolution of individual base pairs — reconstructing when and where each variant arose, how it spread, and whether natural selection favoured, opposed or ignored it.

This evolutionary reconstruction matters for medicine because natural selection has not acted uniformly across human populations. As human groups dispersed across the globe, they encountered different climates, diets and pathogens, and selection left different marks on their genomes. Some of these marks explain population differences in disease risk and drug response that cannot be understood from association studies alone. At the same time, regions of the genome that have been accelerated or constrained along the human lineage point to the genetic basis of traits that distinguish us from other primates — brain size, language, extended lifespan — and to the regulatory networks whose disruption underlies neurodevelopmental and psychiatric disorders. By combining pangenome assemblies, structural variant catalogues and evolutionary rate analyses, we aim to connect the deep history of every segment of the human genome to its present-day consequences for health and disease.