@article{21409,
  abstract     = {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.},
  author       = {Presgraves, Daven C. and Dawe, R. Kelly and Dyer, Kelly A. and Fishman, Lila and Bhide, Soumitra A. and Bradshaw, Sasha L. and Brady, Meghan J. and Burga, Alejandro and Courret, Cécile and Fagen, Brandon L. and Machado Ferretti, Ana Beatriz Stein and Kelemen, Réka K and Kitano, Jun and Liu, Yiran and Martí, Emiliano and Erlenbach, Theresa and Reinhardt, Josephine A. and Ross, Laura and Runge, Jan Niklas and Swanepoel, Callie M. and Vicoso, Beatriz and Vogan, Aaron A. and Lindholm, Anna K. and Larracuente, Amanda M. and Unckless, Robert L.},
  issn         = {1537-1719},
  journal      = {Molecular Biology and Evolution},
  number       = {2},
  publisher    = {Oxford University Press},
  title        = {{The evolutionary genomics of meiotic drive}},
  doi          = {10.1093/molbev/msag020},
  volume       = {43},
  year         = {2026},
}

@article{20796,
  abstract     = {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.},
  author       = {Paouneskou, Dimitra and Baudrimont, Antoine and Kelemen, Réka K and Elkrewi, Marwan N and Graf, Angela and Moukbel Ali Aldawla, Shehab and Kölbl, Claudia and Tiemann-Boege, Irene and Vicoso, Beatriz and Jantsch, Verena},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  publisher    = {Springer Nature},
  title        = {{BAF-1–VRK-1 mediated release of meiotic chromosomes from the nuclear periphery is important for genome integrity}},
  doi          = {10.1038/s41467-025-65420-9},
  volume       = {16},
  year         = {2025},
}

@phdthesis{17119,
  abstract     = {Genomes are shaped by natural selection at the level of the organism, as genomic variants that
have a beneficial effect on the viability or fecundity of their carriers are on average expected
to be passed on to more offspring than less beneficial alleles. However, selection also favors
genomic variants that drive their own transmission to the next generation above the mendelian
expectation of 50 percent in heterozygotes, even if these self-promoting variants are less
beneficial to the organism than other variants at the same locus. Such variants, called meiotic
drivers, are found in diverse taxa, and often impose fitness costs on their host organisms. As
meiotic drivers often require multiple genes and sequences for transmission ratio distortion,
they are often found in regions of low recombination, such as inversions, which prevent their
recombination with the non-driving homologous regions. Reduced recombination rates are
expected to lead to the accumulation of deleterious mutations, which may affect hundreds
of genes trapped in the inversions of meiotic drivers. Although the observed fitness costs of
self-promoting haplotypes are thought to possibly reflect sequence degeneration, no study has
systematically investigated the level of degeneration on a meiotic driver. Further, the low
rates of recombination between driving and non-driving haplotypes have limited the power of
traditional genetic studies in uncovering the gene content of meiotic drivers, and made the
the identification of the genes causing transmission ratio distortion difficult.
After an introduction to meiotic drivers in Chapter 1, this thesis presents three studies that
make use of next generation sequencing data to characterize the sequence and expression
evolution of genes on the t-haplotype, a large and ancient meiotic driver in house mice that is
transmitted to up to 100% of the offspring in males heterozygous for it. Chapter 2 presents
a comprehensive assessment of the t-haplotype’s sequence evolution, which shows signs of
sequence degeneration counteracted by occasional recombination with the non-driving homolog
over large parts of the meiotic driver, proposing an explanation for its long-term survival.
Chapter 3 investigates the sequence and expression evolution of genes on the t-haplotype,
and finds widespread expression and copy number changes and signs of less efficient purifying
selection compared to the genes on the non-driving homolog. Further, this chapter finds
candidates for involvment in drive: two positively selected genes on the t-haplotype, and
the discovery of a t-specific gene duplicate, which was gained from another chromosome,
and which acquired novel sequence and testis-specific expression on the t-haplotype. Finally,
Chapter 4 provides unprecedented insights into the gene expression landscape in testes of
t-carrier mice, using single nucleus sequencing. Cell-resolved RNA-sequencing allows the
comparison of expression in spermatids carrying or not carrying the t-haplotype as well as the
timing of t-haplotype-induced expression changes along spermatogenesis. This study shows
the timing of previously found drive-associated genes, and uncovers novel candidate genes and
biological processes that may underlie the complex biology of transmission ratio distortion of
the t-haplotype. Chapter 5 synthesizes the findings of the three studies, and discusses them in
the context of the current state of meiotic drive research.},
  author       = {Kelemen, Réka K},
  isbn         = {978-3-99078-039-8},
  issn         = {2663-337X},
  keywords     = {meiotic driver, neofunctionalization, single nucleus sequencing},
  pages        = {105},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Characterizing the sequence and expression evolution of the t-haplotype, a model meiotic driver}},
  doi          = {10.15479/at:ista:17119},
  year         = {2024},
}

@article{10767,
  abstract     = {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.},
  author       = {Kelemen, Réka K and Elkrewi, Marwan N and Lindholm, Anna K. and Vicoso, Beatriz},
  issn         = {1471-2954},
  journal      = {Proceedings of the Royal Society B: Biological Sciences},
  number       = {1968},
  pages        = {20211985},
  publisher    = {The Royal Society},
  title        = {{Novel patterns of expression and recruitment of new genes on the t-haplotype, a mouse selfish chromosome}},
  doi          = {10.1098/rspb.2021.1985},
  volume       = {289},
  year         = {2022},
}

@article{6983,
  abstract     = {Malaria, a disease caused by parasites of the Plasmodium genus, begins when Plasmodium-infected mosquitoes inject malaria sporozoites while searching for blood. Sporozoites migrate from the skin via blood to the liver, infect hepatocytes, and form liver stages which in mice 48 h later escape into blood and cause clinical malaria. Vaccine-induced activated or memory CD8 T cells are capable of locating and eliminating all liver stages in 48 h, thus preventing the blood-stage disease. However, the rules of how CD8 T cells are able to locate all liver stages within a relatively short time period remains poorly understood. We recently reported formation of clusters consisting of variable numbers of activated CD8 T cells around Plasmodium yoelii (Py)-infected hepatocytes. Using a combination of experimental data and mathematical models we now provide additional insights into mechanisms of formation of these clusters. First, we show that a model in which cluster formation is driven exclusively by T-cell-extrinsic factors, such as variability in “attractiveness” of different liver stages, cannot explain distribution of cluster sizes in different experimental conditions. In contrast, the model in which cluster formation is driven by the positive feedback loop (i.e., larger clusters attract more CD8 T cells) can accurately explain the available data. Second, while both Py-specific CD8 T cells and T cells of irrelevant specificity (non-specific CD8 T cells) are attracted to the clusters, we found no evidence that non-specific CD8 T cells play a role in cluster formation. Third and finally, mathematical modeling suggested that formation of clusters occurs rapidly, within few hours after adoptive transfer of CD8 T cells, thus illustrating high efficiency of CD8 T cells in locating their targets in complex peripheral organs, such as the liver. Taken together, our analysis provides novel insights into and attempts to discriminate between alternative mechanisms driving the formation of clusters of antigen-specific CD8 T cells in the liver.},
  author       = {Kelemen, Réka K and Rajakaruna, H and Cockburn, IA and Ganusov, VV},
  issn         = {1664-3224},
  journal      = {Frontiers in Immunology},
  publisher    = {Frontiers},
  title        = {{Clustering of activated CD8 T cells around Malaria-infected hepatocytes is rapid and is driven by antigen-specific cells}},
  doi          = {10.3389/fimmu.2019.02153},
  volume       = {10},
  year         = {2019},
}

@article{542,
  abstract     = {The t-haplotype, a mouse meiotic driver found on chromosome 17, has been a model for autosomal segregation distortion for close to a century, but several questions remain regarding its biology and evolutionary history. A recently published set of population genomics resources for wild mice includes several individuals heterozygous for the t-haplotype, which we use to characterize this selfish element at the genomic and transcriptomic level. Our results show that large sections of the t-haplotype have been replaced by standard homologous sequences, possibly due to occasional events of recombination, and that this complicates the inference of its history. As expected for a long genomic segment of very low recombination, the t-haplotype carries an excess of fixed nonsynonymous mutations compared to the standard chromosome. This excess is stronger for regions that have not undergone recent recombination, suggesting that occasional gene flow between the t and the standard chromosome may provide a mechanism to regenerate coding sequences that have accumulated deleterious mutations. Finally, we find that t-complex genes with altered expression largely overlap with deleted or amplified regions, and that carrying a t-haplotype alters the testis expression of genes outside of the t-complex, providing new leads into the pathways involved in the biology of this segregation distorter.},
  author       = {Kelemen, Réka K and Vicoso, Beatriz},
  journal      = {Genetics},
  number       = {1},
  pages        = {365 -- 375},
  publisher    = {Genetics Society of America},
  title        = {{Complex history and differentiation patterns of the t-haplotype, a mouse meiotic driver}},
  doi          = {10.1534/genetics.117.300513},
  volume       = {208},
  year         = {2018},
}