Characterization of Recent Evolutionary Signatures of Genetic Elements involved in Human Pregnancy

Abstract

Eutherian pregnancy is characterized by relatively prolonged gestation and early establishment of direct maternal-fetal contact. In order to support extended growth of a genetically distinct fetus, the maternal immune system experiences immune modulations to allow both effective host defense as well as establishment and maintenance of pregnancy. Involved in such modulations are reproductive immunity genes and potentially, regulatory elements such as enhancers that are expressed in reproductive tissues. Since the origin of modern humans approximately 200,000 to 250,000 years ago, humans have experienced several major events, which have exposed them to novel selective agents. The effects of such events can be found within the genomes of present day humans and therefore, studying the genetic variation within human populations could provide insights into the recent evolution of the genetic elements involved in human pregnancy. In my dissertation, I have used population genetics methods to study the patterns of recent evolution of genetic elements that are associated with human pregnancy. More specifically, I utilized several metrics with power to detect distinct genomic signatures resulting from incidences of recent positive selection. I first studied the patterns of recent evolution in a set of genes that participate in sialic acid biology, to determine if reproductive immunity genes show significant evidence of recent positive selection. While the majority of the sialic acid biology genes do not exhibit significant evidence of recent positive selection, I found that different genes have experienced temporally and spatially varying selection events. Next, I moved my focus to enhancers that are active in 41 tissues, including both reproductive and somatic tissues. I found that approximately 5.90% of enhancers exhibit evidence of recent positive selection. Furthermore, the putative target genes of these enhancers were enriched for immunity-related functions. Together, my work sheds light on the evolutionary history of some of the genetic elements involved in human pregnancy, as well as suggest interesting directions for future research on the evolution of human reproduction.