# Investigating the evolutionary genetics and genomic consequences of sex-ratio meiotic drive in Drosophila > **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2024 · $308,000 ## Abstract Project Summary Eukaryotic genomes contain a diversity of evolutionarily “selfish” genetic elements (SGEs) that obtain transmission advantages at the expense of their host carriers. SGEs tend to use one of two broad strategies: over-replicate relative to the host genome (e.g., transposable elements) or distort fair Mendelian transmission (e.g., meiotic drive elements). Sex chromosomes are especially susceptible to the invasion and accumulation of meiotic drive elements that, by distorting X versus Y chromosome transmission via selective sperm-killing, bias progeny sex ratios. Such “sex-ratio drive” can potentiate evolutionary conflicts of interest between drive genes and drive-suppressors at X-linked, Y-linked, and autosomal loci. Molecular arms races arising from recurrent bouts of such drive-mediated conflict can have far reaching consequences for male fertility, for demography (including the potential risk of unisexual population extinction), for genome evolution, and for speciation. Understanding the genetics, molecular mechanisms, evolutionary dynamics, and genomic consequences of sex-ratio drive is therefore of paramount importance. Here we propose to investigate a system of sex-ratio drive and suppression that evolved recently and then, as expected under molecular arms race dynamics, rapidly diversified among three closely related species of Drosophila— D. simulans, D. mauritiana, and D. sechellia. Our previous work revealed that, while these species diverged ~250 Kya and are today reproductively isolated by numerous genetic incompatibilities, some gene flow has nevertheless occurred among all three. We discovered that the so-called Winters sex- ratio drive system is part of a family of X-linked, satellite DNA-associated, Dox-like (Dxl) drive genes that amplified in copy number and diversified in sequence. These Dxl genes encode predicted DNA-binding sperm-specific histones, which we predict differentially disrupt chromatin remodeling of X- versus Y-bearing spermatid pronuclei during spermiogenesis. Furthermore, we found that each species possesses two hairpin RNA-producing autosomal suppressor genes that produce endogenous small interfering RNAs (esiRNAs) predicted to specialize in the silencing of different subsets of the Dxl gene family. Finally, we discovered that some Dxl genes and suppressors show population genetic signatures of strong recent selection and interspecies gene flow. Our research project aims to combine experimental genetics, molecular biology, third-generation sequencing, and evolutionary genomics methods to dissect Dxl driver- hpRNA suppressor interactions; to determine the genomic binding targets of the Dxl-encoded histones and its implications for the evolution of Y chromosome sequence content; and to infer the evolutionary history and dynamics of Dxl-mediated molecular arms races, including its implications for the evolution of hybrid sterility and interspecific gene flow. ## Key facts - **NIH application ID:** 10892286 - **Project number:** 5R01GM148442-02 - **Recipient organization:** UNIVERSITY OF ROCHESTER - **Principal Investigator:** DAVEN C PRESGRAVES - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $308,000 - **Award type:** 5 - **Project period:** 2023-07-22 → 2027-06-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10892286 ## Citation > US National Institutes of Health, RePORTER application 10892286, Investigating the evolutionary genetics and genomic consequences of sex-ratio meiotic drive in Drosophila (5R01GM148442-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10892286. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*