# High-throughput precision genome editing to characterize natural genetic variants

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $451,671

## Abstract

Project summary
 A major goal of genetics and evolutionary biology is to understand how changes in genotype affect
phenotype. Genetic variants affecting fitness are especially informative for investigating evolution, since natural
selection acts exclusively on these variants. By identifying specific variants that influence fitness, we can begin
to understand the molecular mechanisms driving the incredible adaptations of all organisms to their respective
environments.
 We recently developed an approach that allows us to edit genomes with unprecedented efficiency
(~100%) and throughput. In our initial screen, we measured the fitness effects of 16,000 natural genetic
variants differing between two strains of Saccharomyces cerevisiae. In this pilot experiment, we measured the
effects of each variant in isolation, in a single condition. We found that nearly all strong fitness effects were
from promoter variants, rather than protein-coding regions, and these were especially enriched at transcription
factor binding sites.
 Here we propose to utilize this powerful system to investigate two types of interactions of fundamental
importance: gene-by-environment (GxE) in Aim 1, and gene-by-gene (GxG, or epistasis) in Aim 2.
Understanding the context-dependence of fitness effects will reveal key insights into the evolutionary process
that would be unapproachable without our high-throughput precision genome editing technology.
!

## Key facts

- **NIH application ID:** 9978846
- **Project number:** 5R01GM134228-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Hunter B Fraser
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $451,671
- **Award type:** 5
- **Project period:** 2019-08-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978846

## Citation

> US National Institutes of Health, RePORTER application 9978846, High-throughput precision genome editing to characterize natural genetic variants (5R01GM134228-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9978846. Licensed CC0.

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