Wednesday, January 28, 2026 1/28/2026

The genomic basis of environmental adaptation in house mice

Award Number: R35GM149304
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2023
PERIOD OF PERFORMANCE END DATE: 01/31/2028

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The genomic basis of environmental adaptation in house mice - 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 and 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 28 populations of house mice collected across the Americas from 55° S latitude to 54° N latitude. New inbred lines of mice from different environments form a critical resource for the proposed work. Mice from colder environments 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. We have two major goals for the next five years. First, we will identify the genetic architecture and specific loci underlying complex adaptive traits using (1) QTL mapping with wild-derived inbred lines of mice from different environments, (2) expression studies, including the identification of cis-eQTL, to identify specific genes within broad QTL intervals, (3) studies of chromatin accessibility to identify potential regulatory changes, (4) association studies of traits in large samples of mice from natural populations, and (5) studies of inbred lines reared in different laboratory environments to measure the effects of environmental perturbations on both gene expression and organismal- level traits. Second, we will expand on our previous work studying patterns of SNP variation of wild mice by using a combination of long-read PacBio sequencing of mice from natural populations and long-read PacBio sequencing and Hi-C scaffolding of genomes from wild-derived inbred strains to study structural variation across the genome, including (1) copy-number variation contributing to environmental adaptation, (2) transposable element insertion polymorphisms underlying adaptive differences, and (3) larger structural variants such as inversion polymorphisms. The impact of structural variation on gene expression will be assessed using RNAseq from the same animals. Together this combination of approaches will provide an unparalleled picture of the genomic details underlying polygenic adaptation in mice and will identify the genetic basis of traits likely to be relevant for understanding differences among humans.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $351,875 )
2026	2026	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	000	4	1/7/2026	NON-COMPETING CONTINUATION	$351,875
														Subtotal = $351,875

Issue Date FY: 2025 ( Subtotal = $390,972 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	001	3	2/20/2025	NON-COMPETING CONTINUATION	$351,875
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	002	3	8/5/2025	NON-COMPETING CONTINUATION	$39,097
2025	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	000	2	11/11/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $390,972

Issue Date FY: 2024 ( Subtotal = $390,972 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	000	2	2/8/2024	NON-COMPETING CONTINUATION	$351,875
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	001	2	6/21/2024	NON-COMPETING CONTINUATION	$39,097
														Subtotal = $390,972

Issue Date FY: 2023 ( Subtotal = $390,972 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	000	1	3/24/2023	NEW	$390,972
														Subtotal = $390,972

Grand Total All Awards = $1,524,791

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The genomic basis of environmental adaptation in house mice

Award Number: R35GM149304

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/01/2023

PERIOD OF PERFORMANCE END DATE: 01/31/2028

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