Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States
Jeffrey J Lange
Stowers Institute for Medical Research, Kansas City, United States
Jonathan S Yu
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States
Gerald R Smith
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States
Sue L Jaspersen
Stowers Institute for Medical Research, Kansas City, United States; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, United States
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States; Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, United States
Stowers Institute for Medical Research, Kansas City, United States; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, United States
Meiotic drivers are selfish genes that bias their transmission into gametes, defying Mendelian inheritance. Despite the significant impact of these genomic parasites on evolution and infertility, few meiotic drive loci have been identified or mechanistically characterized. Here, we demonstrate a complex landscape of meiotic drive genes on chromosome 3 of the fission yeasts Schizosaccharomyces kambucha and S. pombe. We identify S. kambucha wtf4 as one of these genes that acts to kill gametes (known as spores in yeast) that do not inherit the gene from heterozygotes. wtf4 utilizes dual, overlapping transcripts to encode both a gamete-killing poison and an antidote to the poison. To enact drive, all gametes are poisoned, whereas only those that inherit wtf4 are rescued by the antidote. Our work suggests that the wtf multigene family proliferated due to meiotic drive and highlights the power of selfish genes to shape genomes, even while imposing tremendous costs to fertility.