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生物学领域的一个关键挑战。 进化生物学从遗传学的早期开始，科学家们就已经理解了 结构变异对表型的影响。染色体变异在自然界中普遍存在。已经表明 在几个生物过程中发挥作用，并与多种性状，包括数量相关， 后代、疾病状态和基因表达的调节。然而，尽管这种普遍性和重要性， 关于结构变异的演变的几个长期存在的问题仍然没有答案。在未来 五年来，我的实验室将推进两条平行和互补的研究路线，重点关注两个主要特征 染色体倒位和性染色体。首先，我的小组会调查 维持倒位的进化力量和倒位中的特定突变， 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 它模拟了携带多态倒位的整个染色体，并用它来量化进化 在疟疾蚊子冈比亚按蚊中作用于倒位的力。这个计算的 基础设施将加深我们对倒位生物学及其在诸如 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励进一步的工作 染色体变异。第二条研究路线使用比较和人口基因组学来测试 对性染色体进化的理论预测，也许是最动态进化的 基因组的区域。我将集中在两个独立进化的性染色体系统在茄属（a 物种属的农业重要性和可观的基因组资源），研究模式和 性染色体分化的克里思。我将制作两个雌雄异株的染色体水平的基因组组合 物种（即，那些有单独的男性和女性个体的人），描述他们的性染色体，并使用 比较的方法来测试基因的运动和关闭性染色体。此外，我将寻找 理论模型预测的性连锁区的两个关键特征：性偏基因的富集 表达和性拮抗多态性的积累。我的研究将利用 研究进化上最近的性染色体系统，获得了关于性染色体起源的独特视角。 性别和性连锁基因组区域的动态，并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。通过 开发基因组分析所需的计算工具，并通过测试 大型基因组特征的进化，这项研究计划将在我们对 基因组结构如何以及为何进化。

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.