Reka K. Kelemen

The t -haplotype is a selfish variant of the mouse chromosome 17. It reaches 90-100% transmission rates in heterozygous (+/ t ) males through a poison-antidote system that disables sperm carrying the homologous (+) haplotype. While several poisons and one antidote have been identified, how these mediate drive, and what additional molecular players are involved, is not fully understood. Here, we characterized patterns of gene expression throughout spermatogenesis in +/ t versus +/+ males using single nucleus RNA sequencing. Genes differentially expressed in early spermatogenesis, when poisons are assumed to be expressed, were enriched for key regulators of sperm motility. These included dyneins, which provide the motor function of sperm flagella, and protein phosphatase 1 (PP1) complex genes, which regulate protein activity through dephosphorylation. Phosphoproteomics of +/ t versus +/+ testes revealed changes in phosphorylation levels of several spermatogenesis proteins, supporting a contribution of dysregulated phosphorylation to the biology of the t -haplotype. In particular, the PP1 component PPP1CC2 itself showed significantly decreased phosphorylation in +/ t testes. Further, we found that dyneins located on both the t -haplotype and the corresponding standard version of chromosome 17 have undergone large increases in sperma-tocyte expression in the house mouse lineage. We argue that this may result from an ongoing arms race between the homologs for transmission rates. Together, these results extend our understanding of the molecular changes associated with the t -haplotype, and highlight the value of integrating various OMICS approaches to investigate the mechanisms and evolutionary consequences of transmission distortion.

Meiotic drivers are selfish genetic elements that gain transmission advantages by distorting equal, Mendelian segregation. For decades, biologists have considered meiotic drivers as interesting, albeit esoteric, case studies. It is now clear, however, that meiotic drive is more common and phylogenetically widespread than previously supposed. Indeed, intensive study of a few well-known cases has begun to reveal the evolutionary genomic consequences of meiotic drive. We argue here that many features of genome evolution, content, and organization that are seemingly inexplicable by organismal adaptation or nearly neutral processes are instead best accounted for by recurrent histories of meiotic drive. We review how meiotic drive can affect the evolution of sequences, gene copy numbers, genes with functions in meiosis and gametogenesis, signatures of “selection,” chromosome rearrangements, and karyotype evolution. We also explore the interactions of meiotic drive elements with other classes of selfish genetic elements, including satellite DNAs, transposable elements, and with the endogenous host genes involved in drive suppression. Finally, we argue that some aspects of drive-mediated genome evolution are now sufficiently well established that we might reverse the direction of discovery—rather than ask how drive affects genome evolution, we can use genome data to discover new putative drive elements.

Rapid prophase chromosome movements ensure faithful alignment of the parental homologous chromosomes and successful synapsis formation during meiosis. These movements are driven by cytoplasmic forces transmitted to the nuclear periphery, where chromosome ends are attached through transmembrane proteins. During many developmental stages a specific genome architecture with chromatin nuclear periphery contacts mediates specific gene expression. Whether chromatin is removed from the nuclear periphery as a consequence of chromosome motions or by a specific mechanism is not fully understood. Here, we identify a mechanism to remove chromatin from the nuclear periphery through vaccinia related kinase (VRK-1)–dependent phosphorylation of Barrier to Autointegration Factor 1 (BAF-1) in Caenorhabditis elegans early prophase of meiosis. Interfering with chromatin removal delays chromosome pairing, impairs synapsis, produces oocytes with abnormal chromosomes and elevated apoptosis. Long read sequencing reveals deletions and duplications in offspring lacking VRK-1 underscoring the importance of the BAF-1–VRK-1 module in preserving genome stability in gametes during rapid chromosome movements.

The t -haplotype of mice is a classical model for autosomal transmission distortion. A largely non-recombining variant of the proximal region of chromosome 17, it is transmitted to more than 90% of the progeny of heterozygous males through the disabling of sperm carrying a standard chromosome. While extensive genetic and functional work has shed light on individual genes involved in drive, much less is known about the evolution and function of the rest of its hundreds of genes. Here, we characterize the sequence and expression of dozens of t -specific transcripts and of their chromosome 17 homologues. Many genes showed reduced expression of the t -allele, but an equal number of genes showed increased expression of their t -copy, consistent with increased activity or a newly evolved function. Genes on the t -haplotype had a significantly higher non-synonymous substitution rate than their homologues on the standard chromosome, with several genes harbouring dN/dS ratios above 1. Finally, the t -haplotype has acquired at least two genes from other chromosomes, which show high and tissue-specific expression. These results provide a first overview of the gene content of this selfish element, and support a more dynamic evolutionary scenario than expected of a large genomic region with almost no recombination.