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The genomic basis of environmental adaptation in mice

小鼠环境适应的基因组基础

基本信息

批准号：
10166869
负责人：
MICHAEL W. NACHMAN
金额：
$ 33.45万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-21 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10166869
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

项目摘要

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的遗传基础的理解大多来自于对简单性状的研究，大部分的表型变异是由一个或几个主效基因控制的。然而，许多进化的过程涉及到复杂性状的变化，这些性状由许多影响小到中等的基因控制。复杂的性状也是人类之间大多数表型差异的基础，包括与人类遗传相关的那些。健康这项拟议中的研究将研究家鼠环境适应的遗传基础， musculus，最好的哺乳动物模型为人类。家鼠最近已经扩展到美洲来自西欧的原生地通过结合自然界中遗传和表型变异的研究，该项目将在实验室中进行杂交的群体中建立基因型和表型之间的明确联系，几个复杂的特征这项工作将利用最近对20个家鼠种群的大规模调查从南纬55°到北纬54°的美洲采集。新的近交系小鼠从不同的环境将用于在普通实验室环境中测量表型，控制十字架来自美洲寒冷环境的老鼠已经进化得越来越大（伯格曼规则）和四肢较短（艾伦规则），符合两个最好的记录生态- 哺乳动物的地理模式此外，来自不同环境的小鼠在许多代谢特征上存在差异，包括活动水平、体重指数和血液化学方面。在这里，我们建立在最近的一个基因组扫描，以四种方式在北美东部的50只小鼠中进行选择。(1)外显子组将是在中等覆盖率下测序，全基因组将在低覆盖率下测序，来自两个横断面的小鼠，一个在北美西部，一个在南美，以确定基因座的基础上，环境适应使用的模型，占人口结构。复制模式在不同的样带将提供更多的选择证据。(2)基因表达的模式将在两个研究野生捕获的小鼠和实验室杂交。顺式作用表达数量性状基因座（cis- eQTL）将有助于查明适应的基因。(3)基因座潜在的表型差异将是利用来自不同环境的小鼠的后代的实验室杂交绘制。(4)最后，将在两个群体中进行关联研究，以更精确地定位潜在的特定基因。表型性状关联也将与等位基因年龄的估计结合使用，以测试多基因几种性状的适应模式。总之，实验室交叉和协会研究将提供联系基因型和表现型之间的关系，在单个基因的水平上进行分辨。的组合本研究采用数量遗传学和群体遗传学方法，适应小鼠，并将确定可能与理解代谢相关的性状的遗传基础人类之间的差异。