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 #
5R01GM074245-09
Application #
8600696
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Eckstrand, Irene A
Project Start
2005-02-01
Project End
2015-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
9
Fiscal Year
2014
Total Cost
$350,421
Indirect Cost
$126,510
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
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
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
Mack, Katya L; Campbell, Polly; Nachman, Michael W (2016) Gene regulation and speciation in house mice. Genome Res 26:451-61
Suzuki, Taichi A; Nachman, Michael W (2015) Speciation and reduced hybrid female fertility in house mice. Evolution 69:2468-81
Phifer-Rixey, Megan; Nachman, Michael W (2015) Insights into mammalian biology from the wild house mouse Mus musculus. Elife 4:
Carneiro, Miguel; Albert, Frank W; Afonso, Sandra et al. (2014) The genomic architecture of population divergence between subspecies of the European rabbit. PLoS Genet 10:e1003519
Sheehan, Michael J; Nachman, Michael W (2014) Morphological and population genomic evidence that human faces have evolved to signal individual identity. Nat Commun 5:4800
Campbell, Polly; Nachman, Michael W (2014) X-y interactions underlie sperm head abnormality in hybrid male house mice. Genetics 196:1231-40
Lüke, Lena; Campbell, Polly; Varea Sánchez, María et al. (2014) Sexual selection on protamine and transition nuclear protein expression in mouse species. Proc Biol Sci 281:20133359
Phifer-Rixey, Megan; Bomhoff, Matthew; Nachman, Michael W (2014) Genome-wide patterns of differentiation among house mouse subspecies. Genetics 198:283-97

Showing the most recent 10 out of 37 publications