# Evolution of Phenotypic Extremes and Mechanisms Governing Inheritance

> **NIH NIH R35** · UNIVERSITY OF WISCONSIN-MADISON · 2021 · $970,385

## Abstract

PROJECT SUMMARY
We propose a research program in evolutionary genetics and genomics that emphasizes two distinct themes.
The first theme focuses on the island rule – the widespread phenomenon of populations evolving unusual body
sizes after colonizing islands. Advances in our laboratory have established mice from Gough Island, the largest
wild house mice in the world, as a tractable system for understanding genetic mechanisms responsible for the
evolution of extreme body size. Through comprehensive characterization of novel congenic strains, we will
identify genes and mutations involved in this instance of the island rule. To elucidate causes and
consequences of gigantism, we will extend this unique system to genetically dissect another trait associated
with evolution on islands: exploratory behavior. This research direction will reveal genetic principles of complex
trait evolution in novel environments.
The second theme centers on recombination, a process that diversifies offspring genomes and ensures proper
chromosomal segregation during meiosis in many species. Using single-cell methods that enable us to quantify
recombination in individuals, we have discovered that house mice evolved substantial differences in genomic
crossover number over short timescales, with females and males showing discordant trajectories. Motivated by
this advance, we will reconstruct the evolutionary dynamics of the recombination landscape in house mice
across genomic scales (from hotspots to whole genomes) and temporal scales (from thousands to millions of
years). To identify cellular processes involved in the evolution of recombination, we will integrate high-
resolution, sex-specific positioning of crossovers with cellular profiling of key meiotic phenotypes. This
research direction will unveil mechanisms that drive the evolution of a primary determinant of genetic variation.
These distinct themes of research showcase a program that exploits the power of genetics and genomics in
house mice to address fundamental evolutionary questions with breadth and depth. Beyond their evolutionary
significance, the traits of interest are connected to common human diseases. Defects in recombination are the
leading genetic cause of birth defects, body size is related to the metabolic syndrome, and exploratory activity
is associated with neurological disorders. Our research offers potential to illuminate these conditions by
deciphering natural variation in the premier genetic model organism for human disease.

## Key facts

- **NIH application ID:** 10084060
- **Project number:** 1R35GM139412-01
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Bret A Payseur
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $970,385
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10084060

## Citation

> US National Institutes of Health, RePORTER application 10084060, Evolution of Phenotypic Extremes and Mechanisms Governing Inheritance (1R35GM139412-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10084060. Licensed CC0.

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