Genetics and evolution of extreme body size in an island population of house mice

描述（由申请人提供）：家鼠（小家鼠）是了解复杂表型遗传变异的最重要的哺乳动物模型系统。由于体型的核心生物学作用以及与形态、生理和生活史特征（包括肥胖和癌症等人类疾病）的普遍相关性，体型已经得到了特别深入的研究。虽然体型变异的遗传学主要是在经典的近交系中研究的，但野生家鼠在广泛的栖息地中也表现出体型的实质性变化。一个特别戏剧性的例子来自岛上的老鼠，它们通常比大陆上的老鼠大得多或小得多。这种现象（称为“岛屿综合症”）在多种哺乳动物中都可以观察到，这就提出了一种普遍机制的可能性。家鼠提供了基因工具和自然变异的强大组合，使其成为了解岛屿综合征的绝佳系统。拟议的研究将使用来自高夫岛的野生家鼠种群，这些家鼠经历了一个特别戏剧性的（大约两倍），快速的，最近的体型增长，来解剖岛上体型进化的遗传学，有三个目的。首先，利用近似贝叶斯方法从微卫星变异的基因组模式重建高夫岛小鼠的殖民历史。其次，来自高夫岛的老鼠和一个密切相关的种群将在一个共同的环境中繁殖，以确认体型差异有遗传成分。第三，利用数量性状位点作图技术，确定Gough岛小鼠体大小快速进化的基因组区域。这项研究将提供一些关于普遍观察到的进化模式的第一个遗传学见解，并有助于将野生小鼠的大小变化遗传学与实验室小鼠和人类的大小变化遗传学联系起来。相关性：这项研究与公共卫生相关，因为它将促进我们对生物医学模式生物体型变化的遗传基础的理解，并为人类体型相关疾病（如肥胖和癌症）提供候选基因组区域。

DESCRIPTION (provided by applicant): The house mouse (Mus musculus) is the foremost mammalian model system for understanding genetic variation in complex phenotypes. Body size has been especially well studied because of its central biological role and pervasive correlations with morphological, physiological and life-history traits, including human diseases such as obesity and cancer. Although the genetics of body size variation has been mostly studied in classical inbred strains, wild house mice also show substantial variation in body size across a wide range of habitats. A particularly dramatic example comes from mice on islands, which are usually much larger or smaller than their mainland counterparts. This phenomenon (termed the "island syndrome") is observed across a diversity of mammals, raising the possibility of a general mechanism. The house mouse offers a powerful combination of genetic tools and natural variation, making it an excellent system for understanding the island syndrome. The proposed research will use a wild population of house mice from Gough Island that has experienced an especially dramatic (approximately twofold), rapid, and recent increase in body size to dissect the genetics of body size evolution on islands, with three aims. First, the colonization history of Gough Island mice will be reconstructed from genomic patterns of microsatellite variation using an approximate Bayesian approach. Second, mice from Gough Island and a closely related population will be bred in a common environment to confirm that body size differences have a genetic component. Third, genomic regions responsible for the rapid evolution of body size in mice from Gough Island will be identified using quantitative trait locus mapping. This research will provide some of the first genetic insights into a commonly observed evolutionary pattern and help connect the genetics of size variation in wild mice to that in laboratory mice and humans. Relevance: This study is relevant to public health because it will advance our understanding of the genetic basis of body size variation in a biomedical model organism and provide candidate genomic regions for size-related diseases, such as obesity and cancer, in humans.