Zanders, S. | bioRxiv Science

bioRxiv2021

S. pombe wtf genes use dual transcriptional regulation and selective protein exclusion from spores to cause meiotic drive

Meiotic drivers bias gametogenesis to ensure their transmission into more than half the offspring of a heterozygote. In Schizosaccharomyces pombe, wtf meiotic drivers destroy the meiotic products (spores) that do not inherit the driver from a heterozygote, thereby reducing fertility. wtf drivers encode both a Wtfpoison protein and a Wtfantidote protein using alternative transcriptional start sites. Here, we analyze how the expression and localization of the Wtf proteins are regulated to achieve drive. We show that transcriptional timing and selective protein exclusion from developing spores ensure that all spores are exposed to Wtf4poison, but only the spores that inherit wtf4 receive a dose of Wtf4antidote sufficient for survival. In addition, we show that the Mei4 transcription factor, a master regulator of meiosis, controls the expression of the wtf4poison transcript. This dual transcriptional regulation, which includes the use of a critical meiotic transcription factor, likely complicates the universal suppression of wtf genes without concomitantly disrupting spore viability. We propose that these features contribute to the evolutionary success of the wtf drivers. Author SummaryKiller meiotic drivers are one type of selfish DNA sequence. When only one copy of a killer meiotic driver is found in a genome, the driver is expected to be transmitted to only half of the gametes (e.g. eggs or sperm). Killer meiotic drivers, however, kill developing gametes that do not inherit them, giving the driver a transmission advantage into the next generation. The molecular mechanisms used by these killers are not well understood. In this work, we analyzed how one killer meiotic driver, wtf4 from fission yeast, ensures targeted gamete (spore) killing. Previous work showed that wtf meiotic drivers encode a poison protein that is transmitted to all spores and an antidote protein that rescues only spores that inherit the locus. Here, we show that different timing of the expression of the two proteins, combined with differential inclusion of the proteins in developing spores, both contribute to targeted spore killing. We also demonstrate that wtf4 exploits an essential gene expression pathway, making it difficult for the genome to prevent this locus from being expressed and killing. This extends our knowledge both of how these genetic parasites act and how they are equipped to evade host suppression mechanisms.

genetics↗

bioRxiv2019

Dramatically diverse S. pombe wtf meiotic drivers all display high gamete-killing efficiency

Meiotic drivers are selfish genetic loci that force their transmission into more than 50% of the viable gametes made by heterozygotes. Meiotic drivers are known to cause infertility in a diverse range of eukaryotes and are predicted to affect the evolution of genome structure and meiosis. The wtf gene family of Schizosaccharomyces pombe includes both meiotic drivers and drive suppressors and thus offers a tractable model organism to study drive systems. Currently, only a handful of wtf genes have been functionally characterized and those genes only partially reflect the diversity of the wtf gene family. In this work, we functionally test 22 additional wtf genes. We identify eight new drivers that share between 30-90% amino acid identity with previously characterized drivers. Despite the vast divergence between these genes, they generally drive into >85% gametes when heterozygous. We also find three new wtf genes that suppress drive, including two that also act as autonomous drivers. Additionally, we find that wtf genes do not underlie a weak (64%) transmission bias caused by a locus or loci on chromosome 1. Finally, we find that some Wtf proteins have expression or localization patterns that are distinct from the poison and antidote proteins encoded by drivers and suppressors, suggesting some wtf genes may have non-meiotic drive functions. Overall, this work expands our understanding of the wtf gene family and the burden selfish driver genes impose on S. pombe.\n\nArticle SummaryDuring gametogenesis, the two gene copies at a given locus, known as alleles, are each transmitted to 50% of the gametes (e.g. sperm). However, some alleles cheat so that they are found in more than the expected 50% of gametes, often at the expense of fertility. This selfish behavior is known as meiotic drive. Some members of the wtf gene family in the fission yeast, Schizosaccharomyces pombe, kill the gametes (spores) that do not inherit them, resulting in meiotic drive favoring the wtf allele. Other wtf genes act as suppressors of drive. However, the wtf gene family is diverse and only a small subset of the genes has been characterized. Here we analyze the functions of other members of this gene family and found eight new drivers as well as three new suppressors of drive. Surprisingly, we find that drive is relatively insensitive to changes in wtf gene sequence as highly diverged wtf genes execute gamete killing with similar efficiency. Finally, we also find that the expression and localization of some Wtf proteins are distinct from those of known drivers and suppressors, suggesting that these proteins may have non-meiotic drive functions.

genetics↗