# The genomic basis of environmental adaptation in house mice

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA BERKELEY · 2024 · $390,972

## Abstract

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 adaptat...

## Key facts

- **NIH application ID:** 10814811
- **Project number:** 5R35GM149304-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** MICHAEL W. NACHMAN
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $390,972
- **Award type:** 5
- **Project period:** 2023-04-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10814811

## Citation

> US National Institutes of Health, RePORTER application 10814811, The genomic basis of environmental adaptation in house mice (5R35GM149304-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10814811. Licensed CC0.

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