Evolution of Phenotypic Extremes and Mechanisms Governing Inheritance

项目摘要 我们提出了一个进化遗传学和基因组学的研究计划，强调两个不同的主题。 第一个主题集中在海岛法则--种群进化的普遍现象异常体 殖民岛屿后的大小。我们实验室的进步已经建立了来自戈夫岛的小鼠， 野生家鼠在世界上，作为一个易于处理的系统，了解遗传机制负责 极端体型的进化通过对新型同源菌株的全面表征，我们将 确定与这个岛屿规则有关的基因和突变。阐明原因， 我们将扩展这个独特的系统，从基因上剖析另一个与之相关的特征。 探索性行为。这一研究方向将揭示复杂的遗传学原理 新环境中的性状进化 第二个主题是重组，这是一个使后代基因组多样化并确保适当的基因组的过程。 许多物种减数分裂时染色体分离。使用单细胞方法，使我们能够量化 在个体中的重组，我们发现家鼠在基因组中进化出了实质性的差异， 在短时间尺度上的交叉数量，女性和男性显示出不一致的轨迹。出于 这一进展，我们将重建家鼠重组景观的进化动力学 跨基因组尺度（从热点到整个基因组）和时间尺度（从数千到数百万）， 年）。为了确定参与重组进化的细胞过程，我们将整合高- 分辨率，性别特异性定位的交叉与细胞分析的关键减数分裂表型。这 研究方向将揭示驱动遗传变异主要决定因素进化的机制。 这些独特的研究主题展示了一个利用遗传学和基因组学的力量， 以广泛和深入地解决基本的进化问题。超越其进化 重要的是，感兴趣的性状与常见的人类疾病有关。重组中的缺陷是 导致出生缺陷的遗传原因，身体大小与代谢综合征，探索活动有关 与神经系统疾病有关我们的研究提供了通过以下方式阐明这些条件的潜力： 破译人类疾病的首要遗传模式生物的自然变异。

PROJECT SUMMARY We propose a research program in evolutionary genetics and genomics that emphasizes two distinct themes. The first theme focuses on the island rule – the widespread phenomenon of populations evolving unusual body sizes after colonizing islands. Advances in our laboratory have established mice from Gough Island, the largest wild house mice in the world, as a tractable system for understanding genetic mechanisms responsible for the evolution of extreme body size. Through comprehensive characterization of novel congenic strains, we will identify genes and mutations involved in this instance of the island rule. To elucidate causes and consequences of gigantism, we will extend this unique system to genetically dissect another trait associated with evolution on islands: exploratory behavior. This research direction will reveal genetic principles of complex trait evolution in novel environments. The second theme centers on recombination, a process that diversifies offspring genomes and ensures proper chromosomal segregation during meiosis in many species. Using single-cell methods that enable us to quantify recombination in individuals, we have discovered that house mice evolved substantial differences in genomic crossover number over short timescales, with females and males showing discordant trajectories. Motivated by this advance, we will reconstruct the evolutionary dynamics of the recombination landscape in house mice across genomic scales (from hotspots to whole genomes) and temporal scales (from thousands to millions of years). To identify cellular processes involved in the evolution of recombination, we will integrate high- resolution, sex-specific positioning of crossovers with cellular profiling of key meiotic phenotypes. This research direction will unveil mechanisms that drive the evolution of a primary determinant of genetic variation. These distinct themes of research showcase a program that exploits the power of genetics and genomics in house mice to address fundamental evolutionary questions with breadth and depth. Beyond their evolutionary significance, the traits of interest are connected to common human diseases. Defects in recombination are the leading genetic cause of birth defects, body size is related to the metabolic syndrome, and exploratory activity is associated with neurological disorders. Our research offers potential to illuminate these conditions by deciphering natural variation in the premier genetic model organism for human disease.