Computational tools and quantitative analyses of genome structure evolution

基因组结构进化的计算工具和定量分析

基本信息

批准号：
10686401
负责人：
Rafael F Guerrero
金额：
$ 37.14万
依托单位：
NORTH CAROLINA STATE UNIVERSITY RALEIGH
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-18 至 2027-06-30
项目状态：
未结题

项目摘要

ABSTRACT Understanding the forces that drive structural changes in the genome remains a key challenge in genetics and evolutionary biology. Since the earliest days of genetics, scientists have understood the vast implications that structural variation has on phenotypes. Chromosomal variation is ubiquitous across nature. It has been shown to play a role in several biological processes and is associated with multiple traits, including number of offspring, disease states, and the regulation of gene expression. Yet, despite this ubiquity and importance, several longstanding questions about the evolution of structural variation remain unanswered. Over the next five years, my lab will advance two parallel and complementary research lines that focus on two major features of the genomic landscape: chromosome inversions and sex chromosomes. First, my group will investigate the evolutionary forces maintaining inversions and the specific mutations within inversions that underlie important phenotypes. To this end, I will create and deploy a full-featured open-source software package that simulates whole chromosomes that carry polymorphic inversions and use it to quantify evolutionary forces acting on inversions in the malaria mosquito Anopheles gambiae. This proposed computational infrastructure will deepen our understanding of the biology of inversions and their role in processes like adaptation and speciation, and will motivate further work by allowing the rapid simulation of genome-scale data with chromosomal variation. A second research line uses comparative and population genomics to test theoretical predictions on the evolution of sex chromosomes, perhaps the most dynamically evolving region of the genome. I will focus on two independently evolved sex-chromosome systems in Solanum (a speciose plant genus of agricultural importance and considerable genomic resources), to study the mode and tempo of sex chromosome divergence. I will produce chromosome-level genome assemblies for two dioecious species (i.e., those with separate male and female individuals), characterize their sex chromosomes, and use a comparative approach to test for gene movement on and off the sex chromosomes. Further, I will search for two key features of the sex-linked regions predicted by theoretical models: an enrichment of sex-biased gene expression and an accumulation of sexually antagonistic polymorphism. My research will leverage the benefits of working with evolutionarily recent sex-chromosome systems, gaining a unique perspective on the origin of sex and the dynamics of sex-linked genomic regions, and learning about the conditions that affect the evolution of recombination suppression, subsequent sex-chromosome divergence, and potential degeneration. By developing computational tools necessary for genomic analysis and by testing core hypotheses of the evolution of large genomic features, this research program will make important strides in our understanding of how and why the structure of the genome evolves.

抽象的了解驱动基因组结构变化的力量仍然是遗传学和生物医学领域的一个关键挑战进化生物学。从遗传学的早期开始，科学家们就已经了解了以下方面的巨大影响：结构变异对表型有影响。染色体变异在自然界中普遍存在。已经显示了在多种生物过程中发挥作用，并与多种特征相关，包括数量后代、疾病状态和基因表达的调节。然而，尽管如此普遍且重要，关于结构变异演化的几个长期存在的问题仍未得到解答。在接下来的五年内，我的实验室将推进两条平行且互补的研究路线，重点关注两个主要特征基因组景观：染色体倒位和性染色体。首先，我的小组将进行调查维持倒置的进化力量以及倒置背后的特定突变重要的表型。为此，我将创建并部署一个功能齐全的开源软件包模拟携带多态性倒转的整个染色体并用它来量化进化作用于疟疾蚊子冈比亚按蚊反转的力。这个提议的计算基础设施将加深我们对反转生物学及其在诸如此类的过程中的作用的理解适应和物种形成，并将通过允许快速模拟基因组规模的数据来激发进一步的工作具有染色体变异。第二条研究线使用比较和群体基因组学来测试对性染色体进化的理论预测，也许是进化最动态的基因组的区域。我将重点关注茄属中两个独立进化的性染色体系统（a 具有农业重要性和大量基因组资源的物种植物属），以研究模式和性染色体分歧的速度。我将为两个雌雄异株的染色体水平基因组组装物种（即具有独立男性和女性个体的物种），表征其性染色体，并使用测试性染色体内外基因运动的比较方法。此外，我将寻找理论模型预测的性别连锁区域的两个关键特征：性别偏向基因的富集性拮抗多态性的表达和积累。我的研究将利用这些好处研究进化上最近的性染色体系统，获得关于性染色体起源的独特视角性别和与性别相关的基因组区域的动态，以及了解影响进化的条件重组抑制、随后的性染色体分歧和潜在的退化。经过开发基因组分析所需的计算工具并测试核心假设大基因组特征的进化，这项研究计划将在我们的理解方面取得重要进展基因组结构如何以及为何进化。