Computational tools and quantitative analyses of genome structure evolution

摘要 理解驱动基因组结构变化的力量仍然是遗传学和 进化生物学。从遗传学最早的日子起，科学家们就已经理解了 结构变异对表型有影响。染色体变异在自然界中无处不在。它已经被证明了 在几个生物过程中发挥作用，并与多种特征有关，包括数量 后代、疾病状态和基因表达的调节。然而，尽管这种无处不在和重要， 关于结构变异演化的几个长期问题仍未得到解答。在接下来的时间 五年来，我的实验室将推进两条平行和互补的研究路线，专注于两个主要特征 基因组图景：染色体倒置和性染色体。首先，我的团队将调查 维持反转的进化力量和反转中的特定突变 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 它模拟携带多态倒置的整个染色体，并用它来量化进化 作用于疟疾蚊子冈比亚按蚊的倒置的力量。这一建议的计算 基础设施将加深我们对倒置生物学及其在以下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推动进一步的工作 伴随着染色体变异。第二条研究路线使用比较基因组学和群体基因组学来测试 关于性染色体进化的理论预测，可能是进化最动态的 基因组的区域。我将把重点放在茄子的两个独立进化的性染色体系统上(a 具有重要农业价值和丰富的基因组资源的特殊植物属)，研究模式和 性染色体分化的节奏。我将为两个雌雄异株生产染色体水平的基因组组件 物种(即那些具有独立的男性和女性个体的物种)，描述他们的性染色体，并使用 比较方法测试基因在性染色体上和在性染色体外的运动。更进一步，我会搜索 理论模型预测的性别相关区域的两个关键特征：性别偏见基因的丰富 表达和积累性拮抗的多态。我的研究将充分利用 利用进化上最新的性染色体系统，获得了关于人类起源的独特视角 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，随之而来的性染色体分裂，以及潜在的退化。通过 开发基因组分析所需的计算工具，并通过测试 大基因组特征的进化，这一研究计划将在我们对 基因组结构是如何以及为什么进化的。

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.