Grant: Discovery Grants Program - Individual

Background: Sex determination is the process by which a bipotential gonad is directed towards becoming a testis or ovary, while sexual differentiation is the suite of downstream events that lead to the eventual production of sperm/eggs as well as secondary sexual traits. In recent years, it has become clear that these processes are more dynamic than previously appreciated. In mammals, sex determination is relatively controlled due to the existence of heteromorphic sex chromosomes (XX/XY) and by the tightly controlled action of genes stimulating male vs female pathways. In lower vertebrates, however, including fish, the mechanisms and genes involved in sex determination are more diverse and often exhibit interactions between environmental and genetic factors. My research group is working on understanding the genes involved in sex determination and differentiation in the oldest lineage of vertebrates, jawless fish, specifically lampreys. Lamprey are fantastic models of the early vertebrate genome and body because they diverged a long time ago from other vertebrates (~ 550 million years), yet harbour many vertebrate specific traits, including core aspects of vertebrate reproduction and gonad development. Long elusive, we recently found that sex determination in lampreys likely revolves around expression of genes in special germline restricted chromosomes (GRCs), which are extra chromosomes present only in the germ cells that will become future egg/sperm. Since GRCs are not expressed in somatic cells, they may evolve in unique ways, like sex chromosomes. Objectives:  The first objective of my research program is to identify the temporal window when sex determination occurs in sea lamprey and then perform single-cell RNA-sequencing of gonads flanking this window to characterize cell-specific changes in gene expression. This molecular data will be combined with histological data to probe the precise location where key genes are expressed in the gonad. Next, I hypothesize that i) genes involved in sex determination and differentiation in lampreys are novel to vertebrates; ii) the GRC's evolve like Y-chromosomes; and iii) gene expression is more constrained during early vs late stages of gonad development. These hypotheses will be explored by i) comparing the genomes of lampreys relative to those in ancestral, older, vertebrates (amphioxus) and to younger ones (e.g. chicken); ii) comparing the evolutionary dynamics of the GRCs in multiple species of northern lampreys and; iii) comparing plasticity in gene expression across gonad development. Impact: This research will strengthen our understanding of the core components of sexual reproduction in vertebrates and contribute to the literature on the complexity and non-binary nature of sex determination and differentiation. From an applied point of view, it aligns with the mission of a governmental agencies to explore strategies to control fertility of invasive sea lampreys in the upper Great Lakes.