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

Abstract

Meiotic drivers are selfish alleles that can 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 for meiotic drive phenotypes. 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% of gametes when heterozygous. We also identify three wtf genes that suppress other wtf drivers, including two that also act as autonomous drivers. Additionally, we find that wtf genes do not underlie a weak (64% allele transmission) meiotic driver 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.

Atypical meiosis can be adaptive in outcrossedS. pombedue towtfmeiotic drivers

“…We refer to this diploid as the “double driver heterozygote” (Figure 2B). Importantly, all four of the drivers in this strain are functional and cannot fully suppress any of the other three drivers (Figure 2—figure supplement 1) (Bravo Núñez et al, 2018; Bravo Núñez et al, 2020; Nuckolls et al, 2017). Consistent with our hypothesis, we found that 62% of the viable spores generated by the double driver heterozygote inherited both of the parental alleles at ade6 , compared to 4% of the viable spores generated by the control diploid (Figure 2C, compare diploid 13 to 14).…”

“…* indicates p-value <0.05 (G-test [allele transmission and Nat R Hyg R progeny] and Wilcoxon test [fertility]). The data for diploid 14 were previously published in Bravo Núñez et al, 2020. Raw data can be found in Figure 2—figure supplement 4 and Figure 2—figure supplement 5.…”

“…To further determine the contribution of competing wtf drivers to the high level of disomic spores, we decided to test our model in a strain background with more extensive heterozygosity, like those generated by outcrossing. For these experiments, we started with an Sp/Sk mosaic diploid strain that is heterozygous for eight known or predicted wtf meiotic drivers (Bravo Núñez et al, 2020; Eickbush et al, 2019). This mosaic diploid is homozygous for Sk chromosomes 1 and 2 but is heterozygous for most of chromosome 3 for Sp and Sk -derived sequences (Figure 3A).…”

“…In this work, we explore the potential selective pressures meiotic drivers can impose on the evolution of gametogenesis. We use the fission yeast S. pombe as it is infested with multiple meiotic drive genes belonging to the wtf ( w ith Tf ) gene family (Bravo Núñez et al, 2020; Eickbush et al, 2019; Hu et al, 2017; Nuckolls et al, 2017). Each wtf meiotic driver encodes two proteins from two largely overlapping transcripts with distinct start sites: a poison (Wtf poison ) and an antidote (Wtf antidote ) (Hu et al, 2017; Nuckolls et al, 2017).…”

“…Strikingly, even a mistmatch of two amino acids within the C-terminus can disrupt the ability of a Wtf antidote to neutralize a Wtf poison (Bravo Núñez et al, 2018). The antidote of a given wtf gene generally does not neutralize poisons produced by other wtf drivers with distinct sequences (Bravo Núñez et al, 2018; Bravo Núñez et al, 2020; Hu et al, 2017). In diploids heterozygous for wtf loci, these drivers can be described as ‘competing’ as they exist on separate haplotypes.…”