Casting a wider net: Using ray-finned fish genomes to gain novel insights into vertebrate molecular evolution

The past decade has provided unprecedented insights into the molecular evolutionary pathways that have given rise to the present day diversity of vertebrates. Comparative genomic studies have repeatedly revealed that many key ecological traits, novel functional phenotypes, and even disease states are governed by genomic regions characterized by frequent mutations, duplications, or deletion events. However, the evolutionary origins and early diversification history of many of these regions remain poorly understood. My work focuses on providing a resolution to this history, focusing on the evolution of the vertebrate mobilome and a clustered gene family of innate immune receptors with putative links to the origin of the adaptive immune response. To accomplish this, I sequenced the genomes of Polypterus bichir and Lepisosteus osseus, two taxa that fill critical genomic sampling gaps for early diverging vertebrate lineages. Integrating these genomes into a comparative dataset of over 100 genomes that span all major ray-finned fish lineages, I investigated the effect of teleost genome duplication (TGD) on the diversification of the ray-finned fish mobilome. My findings reveal no substantial shift in mobilome composition following the TGD event, in line with a growing body of evidence that this historical ploidy event has not left a signature of a burst of molecular diversification and innovation across half of living vertebrates. I next expanded my taxonomic coverage to include all major vertebrate lineages to investigate the evolutionary origin of signal regulatory proteins (SIRPs) and their ligand CD47. In mammals, SIRPs are essential for regulating macrophage function and have become important targets for cancer therapy. These receptors also contain variable and joining exons and are hypothesized to have arisen in tetrapods out of a complex of innate immune receptor gene families that also gave rise to recombining T-cell receptors and antibody encoding Immunoglobulin domains. My work demonstrates this is not the case. Instead, SIRPs have evolutionary origins coincident with the origin of the adaptive immune response. In contrast, we find no evidence for an ancient origin of the CD47 ligand, which interacts with SIRPs. Instead, CD47 appears to have arisen at the beginning of amniote evolution, suggesting a decoupling of the evolutionary origins of this ligand and receptor pair. These findings provide a new perspective on the origins and diversification of innate immune receptor gene families and their relationship to the emergence of the adaptive immune system.