Understanding how evolutionary forces shape genomic imprinting and affect healthy development

SUMMARY Genomic imprinting, the parent-of-origin-specific monoallelic expression of a subset of genes, is critically important to human gene regulation and the healthy development of the embryo and placenta. Proper regulation of imprinted gene dosage is a key challenge for assisted reproductive technologies. Moreover, several human diseases that affect as many as one in ten thousand live births result from genetic alterations that change the dosage of imprinted genes. Although essential for development, imprinting is thought to evolve rapidly, raising the possibility that the evolution of imprinting affects mammalian development and human disease. Despite a rich body of theory on the evolutionary forces that shape genomic imprinting, almost nothing is known empirically, especially at the molecular level. My overarching goal is to uncover the forces, mechanisms, and molecules underpinning the evolution of imprinting, which will provide novel insights into how this important process works. I will take two approaches to this question. First, I will leverage population genetic tools and publicly available sequencing data to empirically characterize how these evolutionary forces drive the evolution of genomic imprinting. Second, I will perform a focused experimental dissection of disrupted imprinting in deer mouse hybrids. This work will be crucial for understanding gene regulation across generations and within individuals.