Mechanisms of sperm dysfunction by meiotic drive

Meiosis ordinarily ensures the fair segregation of alleles to gametes. Meiotic drivers are selfish genetic elements that subvert this normally fair process and bias their transmission to the next generation, violating the principles of Mendelian inheritance. Drivers are pervasive in sexually reproducing organisms and can spread in populations, even when they harm the host. We know little about the molecular mechanisms of drive but themes emerging from studies of sperm-killing male meiotic drivers implicate chromatin regulation and small RNAs as important factors. This project proposes to study the molecular mechanism of drive in a powerful model system: Segregation Distorter (SD), a sperm killer found in natural populations of Drosophila melanogaster. SD causes sperm dysfunction by inducing a chromatin defect in wild type spermatids containing a sensitive allele of its target—a large block of tandem satellite DNA repeats called Responder (Rsp)—through an unknown mechanism. This proposal studies the molecular basis of the SD- induced sperm chromatin defect and the role of the target in drive sensitivity. The project has two specific aims: 1) to determine the role of Rsp satellite-derived RNA in the mechanism of SD; and 2) to determine the timing and nature of the chromatin phenotype associated with sperm dysfunction. The proposal combines gene editing techniques to manipulate Rsp satellite-derived RNA, with genetic and cytological approaches to quantify the effects on drive strength and chromatin phenotypes. To study the chromatin defect in detail and pinpoint its timing, the proposal uses long-read-based epigenomic assays to study the dynamics of histone marks in driving testes and their controls. The fulfillment of these aims will shed light on mechanisms of drive, dynamic changes in chromatin states in testes, and how satellite DNAs are regulated in the male germline. These insights have broad implications for our understanding of factors influencing male fertility in general and how spermatogenesis is vulnerable to selfish genetic elements. Project Number: 1F31HD121176-01 | Fiscal Year: 2026 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: Logan Edvalson | Institution: UNIVERSITY OF ROCHESTER, ROCHESTER, NY | Award Amount: $50,114 | Activity Code: F31 | Study Section: Special Emphasis Panel[ZRG1 F06A-D (20)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11313173