# Dissecting the genetic basis of selfish sex chromosomes

> **NIH NIH F32** · STOWERS INSTITUTE FOR MEDICAL RESEARCH · 2020 · $65,310

## Abstract

Sex-Ratio (SR) chromosomes are X chromosome variants that subvert the transmission of Y chromosomes,
distort the sex ratio of progeny and gain an evolutionary advantage at a cost to organismal fitness. SR
chromosomes initiate intense genetic conflict between X-linked distorters, Y-linked targets, and an array of
autosomal suppressors. This evolutionary arms race provides a powerful explanation of meiotic sex chromosome
inactivation, turnover of sex chromosomes, and evolution of sex determination systems. SR chromosomes are
thought to target satellite repeats and heterochromatic regions found on degenerate Y chromosomes, yet very
little is known about the specific genetic basis or molecular mechanisms of distortion. This is because SR
systems are primarily known from non-model organisms and are often bound up in complex genomic
rearrangements. 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. I develop two independent methods to circumvent the
confounding effects of chromosomal inversions and dissect the genetic basis underlying this selfish
behavior in closely related Drosophila species.
Specific Aim 1: Developing a mutagenesis approach to identify the genes causing Sex-Ratio distortion
in D. pseudoobscura. Through saturation mutagenesis of SR chromosomes, I identify X-linked of genes
contributing to distortion by screening for reduced transmission. To date, >5,000 lines have been screened (95%
saturation), with 33 lines exhibiting reduced distortion. Using CRISPR-Cas9 genome editing, I propose to test
the necessary and sufficient conditions of resulting candidate loci and place them into a functional pathway for
SR distortion. Specific Aim 2: Engineering 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, these two methods 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 species, and for the first time explicitly test both the evolutionary
conservation hypothesis and the population genetic hypothesis that Sex-Ratio distortion is determined by
epistatically interacting X-linked genes bound together by chromosomal inversions. The proposed research
provides training opportunities in both genomic analyses and genetic engineering, and establishes a stro...

## Key facts

- **NIH application ID:** 10327780
- **Project number:** 7F32GM134707-02
- **Recipient organization:** STOWERS INSTITUTE FOR MEDICAL RESEARCH
- **Principal Investigator:** Spencer A Koury
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,310
- **Award type:** 7
- **Project period:** 2021-03-15 → 2022-03-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10327780

## Citation

> US National Institutes of Health, RePORTER application 10327780, Dissecting the genetic basis of selfish sex chromosomes (7F32GM134707-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10327780. Licensed CC0.

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