My research aims to identify the mechanisms that underpin the evolution of complex phenotypes, such as placentation. My research program integrates genomics, developmental biology, and ecophysiology to understand the mechanism that give rise to the selectable variation that has resulted in the evolution of complex traits. My current project uses transcriptomics to identify the genes underpinning placental functions in live bearing lizards. This research is conducted in a comparative framework to identify if complex placental functions have evolved in independent lineages using the same or different genetic mechanism.
The placenta and the evolution of new organs
Large animals such as humans, are composed of complex organs. Many of our organs, such as the liver, heart, and eye are found in most living vertebrates and therefore originated hundreds of millions of years ago in ancestors that we share with fishes. As these organs evolved a long time ago it is difficult to understand how they originated and what molecular processes were involved in their evolution.
The placenta is a unique example of an organ that has evolved many times independently in animals and evolved relatively recently in some organisms. Whilst the placenta is present in live bearing mammals, placentae are also present in live bearing reptiles and fishes. In each lineage that live birth has evolved, a placenta has evolved to support pregnancy.
By studying the physiology, development, and genomic underpinning of the placenta in vertebrates, my research aims to understand how placentae evolve. By comparing how placentae evolve in different lineages I try to understand what the origins of the placenta allow us to infer about the origin and evolution of organs more broadly in animals.
The evolutionary origin of embryo implantation in mammals
In humans, pregnancy is characterised by dynamic changes in the way the maternal immune system responds to the presence of an embryo. Through the middle of pregnancy, the maternal immune system is suppressed at the maternal-fetal interface, to protect the embryo from the potential rejection by the maternal immune system. However, at the beginning and end of pregnancy, perhaps counter-intuitively, the uterus uses inflammation (a maternal immune response) to regulate key physiological components of implantation and birth. The use of inflammation to regulate the normal physiological processes of implantation and parturition can be seen as a paradox because in the middle of gestation inflammation is the single biggest threat to the maintenance of pregnancy.
To identify why human implantation is facilitated by inflammation my research has looked at marsupials, relatives of eutherian mammals, which have a more ancestral mode of pregnancy. Marsupial pregnancy is short and through most of gestation the embryo is shielded from maternal tissue by the presence of an eggshell coat. At Yale, I have shown that the loss of this eggshell barrier not only coincides with the intimate association of maternal and fetal tissues forming a placenta, but with a complete maternal inflammation response (Griffith et al. 2017, PNAS). Along with molecular signatures of inflammation, I identified other markers of implantation at the fetal maternal interface and showed that global transcriptome changes in the uterus significantly overlap with those changes that happen in the uterus of women at implantation. Together these results have allowed us to identify that implantation is homologous to the uterine changes that occur at term in the opossum.
Parent offspring conflict as a driver of major evolutionary change
During pregnancy, the developing embryo of placental mammals relies entirely on the nutrients provided to it by its mother across the placenta. In egg laying reptiles the embryo relies not on placental nutrients but the provision of egg yolk. Whilst in lizards that give birth to live young, an embryo relies on both the yolk it is provided before development and the nutrients it is provided across the placenta. As the placenta is a combination of both maternal and embryonic tissue, both the mother and embryo have some control over how much nutrients are provided by the mother to the embryo, hence there is room for conflict between these two parties. The embryos want as much nutrients as they can get to make themselves big and strong and the mothers want to make sure they have enough nutrients to give birth to as many fit offspring as they can. Through my research I examine the function and evolution of placental gene expression to understand how conflict has contributed to the evolution of placental nutrition, and how a maternal-embryo arms race may explain some of the current mysteries of placental diversity.