Genomic mechanisms behind rapid evolution of sex determining systems

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Developmental systems drift (DSD) the change in the genetic mechanisms underlying a conserved phenotype is pervasive in biology, yet details of how DSD unfolds remain poorly understood. One system that exhibits DSD is sexual differentiation: the genetic basis of this core developmental process varies widely among species, yet we don't fully understand how or why. The long term goal of this research is to understand how DSD is mediated genetically. The short term objectives are to explore DSD of sex chromosome structure and gene function (Aim 1) and to explore DSD of sex determining genes (Aim 2). We will use African clawed frogs (Xenopus) and close relatives to accomplish these goals because they have diverse genetic systems for sex determination, and because powerful tools exist to experimentally manipulate these systems. Aim 1: Across vertebrates, sex chromosome pairs (X and Y or Z and W) are strikingly variable: in some groups they are virtually indistinguishable, while in others they have marked differences in structure and function (cytological appearance, DNA sequences, and gene content). Why is this the case? Aim 1 will illuminate why sex chromosomes within a species do or do not diverge from one another. This work will integrate information from whole and partial genome sequences, laboratory crosses and wild-caught frogs, and analysis of gene expression. This research will form portions of 3 PhD theses (2 current, 1 recruited). Aim 2: How do crucial genetic interactions underlying conserved phenotypes, such as sex determination, evolve? Aim 2 will address whether evolution of crucial genetic pathways occurs through cooption of genes with conserved functional roles (i.e., related to sex determination) and whether this evolution occurs most frequently through gain or loss of function mutations. This work will use genome editing in Xenopus to explore genetic mechanisms of DSD, include international collaboration, and form portions of 3 PhD theses (1 current, 2 recruited). This proposal examines the genetic basis of an important phenotype (sexual differentiation) that exhibits DSD, and for which the genetic basis is relatively simple to manipulate. An innovative comparative genomics system is proposed for mechanistic exploration of DSD at a whole-chromosome and individual gene level. This work builds on discoveries by current and previous BJE HQP, and will equip HQP with cutting edge skills in bioinformatics and molecular biology. It will answer questions about how DSD occurs (By cooption and/or by involving gain or loss of function?), and whether DSD of sex chromosomes and sex-determining genes are linked (Do non-diverged sex chromosomes have new triggers, or is this related to recombination or sexual antagonism?). Importantly, results will have broad implications for understanding how invariant phenotypes are maintained across species in the context of variable genetic signals.