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

岛上家鼠种群极端体型的遗传和进化

• 批准号: 7800077
• 负责人: Melissa Marie Gray
• 金额: $ 4.56万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7800077
• 关键词: Address; Age; Animal Model; Bayesian Analysis; Biological; Biological Models; Body Size; Breeding; Complex; Coronary heart disease; DNA; Disease; Dissection; Dwarfism; Employee Strikes; Environment; Evolution; Fertility; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Genetic screening method; Genomics; Gigantism; Goals; Habitats; House mice; Human; Inbred Strain; Individual; Island; Laboratories; Laboratory mice; Malignant Neoplasms; Mammals; Maps; Microsatellite Repeats; Mus; Mutation; Obesity; Pattern; Phenotype; Physiological; Population; Public Health; Quantitative Trait Loci; Recording of previous events; Research; Role; Syndrome; System; Time; Variant; base; experience; genetic evolution; human disease; insight; life history; pleiotropism; survivorship; tool; trait

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.

描述（由申请人提供）：家鼠（Mus musculus）是用于理解复杂表型遗传变异的最重要的哺乳动物模型系统。体型因其重要的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）的普遍相关性而得到了特别深入的研究。尽管体型变异的遗传学主要在经典近交系中进行研究，但野生家鼠在广泛的栖息地中也表现出体型的巨大差异。一个特别引人注目的例子来自岛屿上的老鼠，它们通常比大陆上的老鼠大或小得多。这种现象（称为“岛屿综合症”）在多种哺乳动物中都被观察到，这提高了普遍机制的可能性。家鼠提供了遗传工具和自然变异的强大组合，使其成为了解岛屿综合症的绝佳系统。这项拟议的研究将利用来自戈夫岛的一群野生家鼠来剖析岛屿上体型进化的遗传学，这些小鼠的体型最近经历了特别显着（大约两倍）、快速的增长，其目的有三个。首先，将使用近似贝叶斯方法根据微卫星变异的基因组模式重建高夫岛小鼠的定植历史。其次，来自戈夫岛的小鼠和一个密切相关的种群将在共同的环境中繁殖，以确认体型差异具有遗传因素。第三，将使用数量性状基因座作图来识别负责戈夫岛小鼠体型快速进化的基因组区域。这项研究将为常见的进化模式提供一些初步的遗传学见解，并有助于将野生小鼠体型变异的遗传学与实验室小鼠和人类的体型变异联系起来。相关性：这项研究与公共卫生相关，因为它将增进我们对生物医学模型生物体体型变异遗传基础的理解，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。