Genomic mechanisms behind rapid evolution of sex determining systems

发育系统漂移（Developmental systems drift， DSD）是生物学中普遍存在的一种保守表型遗传机制的变化，但关于DSD如何展开的细节仍然知之甚少。表现出性别分化的一个系统是性别分化：这一核心发育过程的遗传基础在不同物种之间差异很大，但我们还不能完全理解如何或为什么。这项研究的长期目标是了解DSD是如何通过基因介导的。短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（非洲爪蟾）及其近亲来完成这些目标，因为它们具有不同的性别决定遗传系统，并且因为存在强大的实验工具来操纵这些系统。******目标1：在脊椎动物中，性染色体对（X和Y或Z和W）是非常不同的：在一些群体中，它们实际上是无法区分的，而在另一些群体中，它们在结构和功能（细胞学外观，DNA序列和基因含量）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内的性染色体会或不会彼此分化。这项工作将整合来自全基因组和部分基因组序列、实验室杂交和野生捕获的青蛙以及基因表达分析的信息。本研究将成为3篇博士论文的一部分（2篇在读，1篇招收）。******目标2：保守表型（如性别决定）背后的关键遗传相互作用是如何进化的？目标2将探讨关键遗传途径的进化是否通过具有保守功能角色（即与性别决定相关）的基因的选择而发生，以及这种进化是否通过功能突变的获得或丧失而最频繁地发生。这项工作将利用爪蟾基因组编辑技术探索DSD的遗传机制，包括国际合作，并形成3篇博士论文（1篇在读，2篇招收）的一部分。******本提案研究了一种重要表型（性别分化）的遗传基础，这种表型表现为DSD，并且遗传基础相对容易操纵。提出了一种创新的比较基因组学系统，用于在全染色体和个体基因水平上对DSD进行机制探索。这项工作建立在目前和以前BJE HQP的发现基础上，并将为HQP提供生物信息学和分子生物学方面的前沿技能。它将回答关于DSD是如何发生的问题（通过合作和/或涉及功能的获得或丧失？），以及性染色体的DSD和性别决定基因是否有联系（未分化的性染色体是否有新的触发因素，或者这与重组或性对抗有关？）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间如何维持不变表型具有广泛的意义

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.**