TY - JOUR T1 - Epistatic selection on a selfish <em>Segregation Distorter</em> supergene: drive, recombination, and genetic load JF - bioRxiv DO - 10.1101/2021.12.22.473781 SP - 2021.12.22.473781 AU - Beatriz Navarro-Domínguez AU - Ching-Ho Chang AU - Cara L. Brand AU - Christina A. Muirhead AU - Daven C. Presgraves AU - Amanda M. Larracuente Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/12/24/2021.12.22.473781.abstract N2 - Meiotic drive supergenes are complexes of alleles at linked loci that together subvert Mendelian segregation to gain preferential transmission. In males, the most common mechanism of drive involves the disruption of sperm bearing alternative alleles. While at least two loci are important for male drive— the driver and the target— linked modifiers can enhance drive, creating selection pressure to suppress recombination. In this work, we investigate the evolution and genomic consequences of an autosomal multilocus, male meiotic drive system, Segregation Distorter (SD) in the fruit fly, Drosophila melanogaster. In African populations, the predominant SD chromosome variant, SD-Mal, is characterized by two overlapping, paracentric inversion on chromosome arm 2R and nearly perfect (~100%) transmission. We study the SD-Mal system in detail, exploring its components, chromosomal structure, and evolutionary history. Our findings reveal a recent chromosome-scale selective sweep mediated by strong epistatic selection for haplotypes carrying Sd, the main driving allele, and one or more factors within the double inversion. While most SD-Mal chromosomes are homozygous lethal, SD-Mal haplotypes can recombine with other, complementing haplotypes via crossing over and with wildtype chromosomes only via gene conversion. SD-Mal chromosomes have nevertheless accumulated lethal mutations, excess non-synonymous mutations, and excess transposable element insertions. Therefore, SD-Mal haplotypes evolve as a small, semi-isolated subpopulation with a history of strong selection. These results may explain the evolutionary turnover of SD haplotypes in different populations around the world and have implications for supergene evolution broadly. ER -