A major goal of evolutionary genetics is to understand how selection shapes patterns of DNA sequence variation, and ultimately, to connect DNA sequence variants to phenotypes that affect fitness. One promising approach to this problem is to study species that have recently expanded their ranges into new environments, to look for correlated changes in allele frequencies and environmental variables. This approach to studying environmental adaptation has been used successfully in Drosophila melanogaster where clinal variation is seen for a variety of different molecular and phenotypic traits across broad latitudinal transects. Recent work on humans has also linked changes in allele frequency to climatic variables in candidate genes for common metabolic disorders, suggesting that this approach may also allow us to identify important disease genes. The house mouse, Mus musculus, provides a unique opportunity to study environmental adaptation in the best mammalian model for humans. The proposed research will sample 260 wild mice representing 26 populations across a range of latitudes and altitudes in both North and South America. The sampling design includes paired transects for both altitude and latitude. All mice will be genotyped using a new Affymetrix SNP chip to identify candidate regions of the genome harboring genes underlying adaptation to different environments and climates. Select genomic regions will then be resequenced to identify allelic variants. Mice offer specific opportunities for functional tests not available in humans. Thus, the proposed work will also establish 16 new inbred strains of mice from extreme environments, sequence their genomes, and provide a preliminary description of their phenotypes. These resources will set the stage for future work linking particular adaptive variants to specific phenotypes, many of which are likely to be relevant for human metabolic disorders.

Public Health Relevance

Genes underlying human metabolic disorders show variation that correlates with climate, suggesting a link between environmental adaptation and disease. Mice are the premier model for humans. Here, we will study environmental adaptation in mice, identify candidate genes, and establish resources for future functional tests of the effects of variants at these genes.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM074245-10
Application #
8789166
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Janes, Daniel E
Project Start
2005-02-01
Project End
2015-12-31
Budget Start
2015-01-01
Budget End
2015-12-31
Support Year
10
Fiscal Year
2015
Total Cost
$350,978
Indirect Cost
$127,068
Name
University of California Berkeley
Department
Zoology
Type
Schools of Arts and Sciences
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Moeller, Andrew H; Suzuki, Taichi A; Phifer-Rixey, Megan et al. (2018) Transmission modes of the mammalian gut microbiota. Science 362:453-457
Mack, Katya L; Ballinger, Mallory A; Phifer-Rixey, Megan et al. (2018) Gene regulation underlies environmental adaptation in house mice. Genome Res 28:1636-1645
Phifer-Rixey, Megan; Bi, Ke; Ferris, Kathleen G et al. (2018) The genomic basis of environmental adaptation in house mice. PLoS Genet 14:e1007672
Mo?kovský, Libor; Janoušek, Václav; Reif, Ji?í et al. (2018) Genomic islands of differentiation in two songbird species reveal candidate genes for hybrid female sterility. Mol Ecol 27:949-958
Suzuki, Taichi A; Martins, Felipe M; Nachman, Michael W (2018) Altitudinal variation of the gut microbiota in wild house mice. Mol Ecol :
Moeller, Andrew H; Suzuki, Taichi A; Lin, Dana et al. (2017) Dispersal limitation promotes the diversification of the mammalian gut microbiota. Proc Natl Acad Sci U S A 114:13768-13773
Mack, Katya L; Nachman, Michael W (2017) Gene Regulation and Speciation. Trends Genet 33:68-80
Sheehan, Michael J; Lee, Victoria; Corbett-Detig, Russell et al. (2016) Selection on Coding and Regulatory Variation Maintains Individuality in Major Urinary Protein Scent Marks in Wild Mice. PLoS Genet 12:e1005891
Suzuki, Taichi A; Nachman, Michael W (2016) Spatial Heterogeneity of Gut Microbial Composition along the Gastrointestinal Tract in Natural Populations of House Mice. PLoS One 11:e0163720
Holmes, Michael W; Hammond, Talisin T; Wogan, Guinevere O U et al. (2016) Natural history collections as windows on evolutionary processes. Mol Ecol 25:864-81

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