# Mapping deep evolutionary divergences in cellular models of stress response

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2023 · $10,266

## Abstract

SUMMARY (No Changes from Parent Award)
Understanding how nature builds new traits is a fundamental goal of evolutionary genetics. Unbiased
experimental dissection of trait variation from the wild has to date used linkage or association mapping, which
are suitable only for crosses between compatible individuals of a given species. In the first funding period of
this methods-development R01, PI Brem developed RH-seq, an approach for the unbiased mapping of
natural trait variation that can be applied to reproductively isolated species. Our RH-seq projects in
invertebrate test cases have put the complex genetics of ancient traits within reach for the first time in the
experimental literature. We now want to advance strategies that investigate deeper themes in complex
genetics between species—namely whether evolution uses concerted molecular mechanisms across the loci
underlying a polygenic adaptation, and how these loci work together to drive phenotype. To test-drive these
approaches, in our first Aim we will use an ecologically relevant model system, a thermotolerance divergence
between yeast species that last shared an ancestor five million years ago. In our second Aim, we will port our
ideas and tools for interspecies genetics to mouse primary cells. The latter will use as a testbed a cell-
autonomous, pro-inflammatory aging program called cellular senescence, which we have found to diverge
between between sister species of mice. We will develop RH-seq for unbiased genetic mapping of
senescence traits, and we will pursue epistatic and molecular mechanisms of the underlying loci as a parallel
to our yeast model. Together, our yeast and mouse projects will advance methods for the analysis of
polygenic traits as they differ between species, and accelerate the dissection of such ancient characters in
systems across Eukarya.

## Key facts

- **NIH application ID:** 10810592
- **Project number:** 3R01GM120430-06S2
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Rachel Beth Brem
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $10,266
- **Award type:** 3
- **Project period:** 2017-05-15 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10810592

## Citation

> US National Institutes of Health, RePORTER application 10810592, Mapping deep evolutionary divergences in cellular models of stress response (3R01GM120430-06S2). Retrieved via AI Analytics 2026-06-15 from https://api.ai-analytics.org/grant/nih/10810592. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*