The genomic basis of environmental adaptation in mice

小鼠环境适应的基因组基础

• 批准号: 9926918
• 负责人: MICHAEL W. NACHMAN
• 金额: $ 33.5万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-21 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9926918
• 关键词: Age; Alberta province; Alleles; Americas; Arizona; Biology; Blood Chemical Analysis; Body Size; Body mass index; Brazil; Candidate Disease Gene; Chromosome Mapping; Climate; Complex; Disease; Ear; Environment; Evolution; Exhibits; Florida; Foundations; Gene Expression; Gene Expression Profile; Gene Expression Regulation; Generations; Genes; Genetic; Genetic Variation; Genetic study; Genome Scan; Genomic Segment; Genomics; Genotype; Geography; Goals; Health; House mice; Human; Inbreeding; Individual; Laboratories; Limb structure; Link; Linkage Disequilibrium Mapping; Liver; Mammals; Maps; Measures; Metabolic; Metabolic Diseases; Metabolism; Modeling; Morphology; Mus; New York; North America; Pattern; Phenotype; Physiology; Population; Population Genetics; Quantitative Genetics; Quantitative Trait Loci; RNA Sequences; Research; Resolution; Role; Sampling; South America; Structure; Study models; Surveys; System; Tail; Testing; Tissues; Variant; Western Europe; Work; environmental adaptation; exome; experimental study; genetic approach; genomic data; insight; novel; trait; whole genome

PROJECT SUMMARY Much of our understanding of the genetic basis of adaptation derives from studies of simple traits in which a large proportion of the phenotypic variation is controlled by one or a few genes of major effect. However, much of evolution involves changes in complex traits that are controlled by many genes of small to modest effect. Complex traits also underlie most phenotypic differences among humans, including those related to human health. The proposed research will study the genetic basis of environmental adaptation in house mice, Mus musculus, the best mammalian model for humans. House mice have recently expanded into the Americas from their native range in Western Europe. By combining studies of genetic and phenotypic variation in natural populations with crosses in the lab, this project will make explicit links between genotype and phenotype for several complex traits. This work will utilize recent large-scale surveys of 20 populations of house mice collected across the Americas from 55° S latitude to 54° N latitude. New inbred lines of mice from different environments will be used to measure phenotypes in a common laboratory environment and to perform controlled crosses. Mice from colder environments in the Americas have evolved to become larger (Bergmann's rule) and have shorter extremities (Allen's rule), conforming to two of the best-documented eco- geographic patterns in mammals. In addition, mice from different environments differ in many metabolic traits, including activity levels, body mass index, and aspects of blood chemistry. Here, we build on a recent genome-scan for selection among 50 mice in Eastern North America in four ways. (1) Exomes will be sequenced at moderate coverage and whole genomes will be sequenced at low coverage in an additional 150 mice from two transects, one in Western North America and one in South America, to identify loci underlying environmental adaptation using models that account for population structure. Replicated patterns in separate transects will provide additional evidence of selection. (2) Patterns of gene expression will be studied in both wild-caught mice and in laboratory crosses. Identification of cis-acting expression quantitative trait loci (cis- eQTL) will help pinpoint genes underlying adaptation. (3) Loci underlying phenotypic differences will be mapped using laboratory crosses of progeny derived from mice from different environments. (4) Finally, association studies will be conducted in two populations to more precisely map specific genes underlying phenotypic traits. Associations will also be used in combination with estimates of allele age to test polygenic modes of adaptation for several traits. Together, laboratory crosses and association studies will provide links between genotype and phenotype with resolution at the level of individual genes. The combination of quantitative-genetic and population-genetic approaches in this study will identify loci underlying polygenic adaptation in mice and will identify the genetic basis of traits likely to be relevant for understanding metabolic differences among humans.

项目摘要 我们对适应遗传基础的大部分理解来自对简单特征的研究 表型变异的很大比例由一个或几个具有重大作用的基因控制。但是，很多 进化涉及复杂性状的变化，这些特征由许多小到适中效应的基因控制。 复杂的特征也是人类中大多数表型差异的基础，包括与人有关的差异 健康。拟议的研究将研究房屋小鼠环境适应的遗传基础 Musculus，人类的最佳哺乳动物模型。房屋老鼠最近扩展到美洲 来自他们在西欧的土著范围。通过结合自然遗传和表型变异的研究 实验室中有十字架的种群，该项目将在基因型和表型之间明确联系 几个复杂的特征。这项工作将利用最近对20只房屋老鼠人群的大规模调查 从55°的纬度到54°n的纬度收集。来自不同的小鼠的新近交系 环境将用于在共同的实验室环境中测量表型并执行 受控十字架。来自美洲寒冷环境的小鼠已经发展起来变得更大 （伯格曼的统治）并有较短的四肢（艾伦的统治），符合两个最有记录的生态 哺乳动物中的地理模式。此外，来自不同环境的小鼠在许多代谢特征中不同， 包括活性水平，体重指数和血液化学方面。在这里，我们建立在最近的 基因组扫描以四种方式在北美东部的50只小鼠中进行选择。 （1）EXOMES将是 在中等覆盖范围和整个基因组中测序将在低覆盖范围内测序150 来自两个横断面的小鼠，一只在北美西部，一只在南美，用于识别基因座的基础 使用解释人口结构的模型的环境适应。单独的复制模式 样带将提供其他选择的证据。 （2）基因表达的模式将在两者中研究 野生的小鼠和实验室十字架。鉴定顺式作用表达定量性状局部（顺式） EQTL）将有助于确定适应性的基因。 （3）基因座的基础表型差异将是 使用来自不同环境的小鼠衍生的后代实验室杂交映射。 （4）最后， 关联研究将在两个人群中进行，以更精确地绘制基础的特定基因 表型特征。关联也将与等位基因年龄的估计值结合使用以测试多基因 多种特征的适应模式。实验室十字和协会研究将共同​​提供联系 在基因型和表型之间具有分辨率在单个基因水平上的分辨率。结合 本研究中的定量遗传和种群遗传学方法将确定局部基础多基因 小鼠的适应，将确定可能与理解代谢有关的特征的遗传基础 人类之间的差异。