# The mechanisms of segregation distortion in Drosophila

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2022 · $305,000

## Abstract

Project Summary
Segregation distorters are selfish genetic elements that operate by over-representing themselves in the mature
gamete pool, thus fundamentally violating Mendel’s law. The evolutionary arms races triggered between
distorter genes and their suppressors have long been recognized as a powerful force that shapes the evolution
of genomes, cells, and species. Despite the ubiquity and importance of segregation distorters, we understand
very little about the genetic basis and molecular mechanisms of this class of selfish genetic elements. A key
barrier in understanding the mechanisms of segregation distorters is that they are present in non-model
systems that lack genetic tools, and are almost always associated with chromosomal inversions that thwart
traditional genetic approaches to gene discovery. Without characterizing the underlying genetic basis and
molecular mechanisms it remains impossible to directly connect the arms race initiated by selfish elements to
broader phenomena in the evolution of meiosis and sex chromosome systems.
Here, we develop two independent methods to side-step traditional barriers presented by chromosomal
inversions to gene discovery, and dissect the genetic basis underlying this selfish behavior in closely related
Drosophila species. In our first aim, we develop a mutagenesis approach to identify the genes causing Sex-
Ratio distortion in D. pseudoobscura. Through a combination of sequencing, in silico complementation, bulked-
segregant mapping, and CRISPR/ Cas9 based editing, we are poised to resolve the complex genetic
architecture that underlies distortion and to identify the complete set of genes, including modifiers and
enhancers, that drive the selfish behavior of the D. pseudoobscura Sex-Ratio chromosome. In our second aim,
we uncover cryptic variation within species for suppressors of distortion. Here, we aim to understand the
molecular arms races between distorters and their suppressors through the identification of the genes and
mechanisms of suppression of segregation distortion, and suppressors of suppressors-of-distortion. In our third
aim, we engineer a synthetic chromosomal inversion to allow recombination mapping of Sex-Ratio distortion in
D. persimilis. This approach adapts the Flp/FRT site-specific recombination tools to generate a perfectly
collinear non-driving chromosome to allow free recombination in the region containing all necessary and
sufficient genes for SR distortion. Once candidate genes are mapped, validated, and organized into a
functional pathway for D. persimilis, a comparative analysis of these two systems will test whether SR
mechanisms are unique or shared. Together, this work will provide the most complete genetic architecture of
sex-linked segregation distorters to date, open the door to understanding the molecular mechanisms of
distortion in two Sex-Ratio systems, and for the first time explicitly test independent or shared origins and
mechanisms of Sex-Ratio distortion i...

## Key facts

- **NIH application ID:** 10369698
- **Project number:** 5R01GM141422-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Nitin Phadnis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $305,000
- **Award type:** 5
- **Project period:** 2021-03-15 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10369698

## Citation

> US National Institutes of Health, RePORTER application 10369698, The mechanisms of segregation distortion in Drosophila (5R01GM141422-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10369698. Licensed CC0.

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