An evolutionary perspective helps us understand human history and can also provide insight into important aspects of human health. My current research focuses on the evolution of genes expressed during pregnancy, a critical developmental period for mammals.
Molecular adaptation in the primate placenta
Differences in the form and function of the placenta directly impact fitness by influencing nutrient transfer from mother to offspring. By facilitating greater nutrient transfer, increased placental invasion has been long thought to underlie key primate adaptations including the uniquely large human brain. My work links evolutionary changes in the Matrix Metalloproteinase 9 gene (MMP9) to increased placental invasion in primates. This provides an adaptive molecular basis for shifts in invasiveness that have important implications for changes in primate brain size and life history patterns.
Evolution of human MMP9MMP9 has evolved adaptively coincident with major shifts in placental invasion in primates. However, the selection pressures acting on MMP9 may have changed during human evolution. Humans are subject to a much higher cancer burden than other primates, largely due to our recent increase in longevity. In addition to underlying placental invasion, MMP9 is an important component of cancer metastasis. This study uses patterns of human genetic variation to determine whether the selection pressures shaping human MMP9 are the same or different than those acting in primates.
Co-evolution of placental invasion and inhibition
Pathologies of insufficient and excessive placental invasion are both leading causes of maternal mortality. The high fitness costs of these disorders indicate the importance of regulating placental invasion. This project aims to determine whether TIMPs, the endogenous inhibitors of MMPs, have co-evolved with MMP9. In addition to characterizing the evolutionary history of the TIMPs, this study has implications for potential tradeoffs between placental invasion and cancer metastasis.
Reconstructing placental evolution
The tremendous amount of morphological variation among mammalian placentae makes it difficult to reconstruct placental evolution, which is important for the way we think about adaptive change. This project uses morphological, genetic, and developmental perspectives to reconstruct patterns of placental evolution in mammals.