Genomic mechanisms behind rapid evolution of sex determining systems

发育系统漂移（DSD）保守表型背后的遗传机制的变化在生物学中是普遍存在的，但DSD如何展开的细节仍然知之甚少。表现出DSD的一个系统是性别分化：这一核心发育过程的遗传基础在物种之间差异很大，但我们并不完全了解如何或为什么。这项研究的长期目标是了解DSD是如何遗传介导的。近期目标是探索性染色体结构和基因功能的DSD（目标1）和性别决定基因的DSD（目标2）。我们将使用非洲爪蛙（Xenopus）及其近亲来实现这些目标，因为它们具有不同的性别决定遗传系统，并且存在强大的工具来实验性地操纵这些系统。目标1：在脊椎动物中，性染色体对（X和Y或Z和W）的变化非常明显：在某些群体中，它们几乎无法区分，而在另一些群体中，它们在结构和功能（细胞学外观，DNA序列和基因内容）上有显著差异。为什么会这样呢？目的1将阐明为什么一个物种的性染色体彼此之间会或不会发生分化。这项工作将整合来自全基因组和部分基因组序列、实验室杂交和野生青蛙以及基因表达分析的信息。本研究将形成3篇博士论文的一部分（2篇当前，1篇招募）。**目的2：如何关键的遗传相互作用下保守的表型，如性别决定，演变？目标2将解决关键遗传途径的进化是否通过具有保守功能作用的基因的共选择发生（即，与性别决定有关）以及这种进化是否最常通过功能突变的获得或丧失而发生。这项工作将使用非洲爪蟾的基因组编辑来探索DSD的遗传机制，包括国际合作，并形成3篇博士论文的一部分（1篇当前，2篇招募）。这项建议检查了一个重要的表型（性分化），表现出DSD，遗传基础是相对简单的操纵的遗传基础。本文提出了一个创新的比较基因组学系统，用于在全染色体和单个基因水平上探索DSD的机制。这项工作建立在当前和以前的BJE HQP发现的基础上，并将为HQP提供生物信息学和分子生物学方面的尖端技能。它将回答有关DSD如何发生的问题（通过选择和/或通过涉及功能的获得或丧失？），以及性染色体和性别决定基因的DSD是否连锁（非分歧性染色体是否有新的触发因素，或者这与重组或性拮抗有关？）。重要的是，这些结果将对理解在可变遗传信号的背景下，物种之间如何保持不变的表型产生广泛的影响。

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.**