Genetics of sterility
wild-derived strains
house mouse
hybrid zone
86
Scopus Publications
Scopus Publications
Beyond the Prdm9 model: independent evolution of hybrid male sterility in house mice Pavla Klusáčková, Agata Woźniewska, Petra Dufková, Beth L. Dumont, Jan M. Wójcik, et al. Heredity, 2026 Hybrid sterility is a critical postzygotic barrier that limits gene flow during speciation, yet the genetic architecture underlying evolution of such barriers in the early stages of speciation remains poorly characterized. In house mice, F1 male sterility observed in crosses between Mus musculus musculus and M. m. domesticus has been attributed to incompatibilities between heterozygous autosomal Prdm9 , which controls primarily the position of recombination hotspots, and copy number variation in X-linked Mir465 miRNA genes. This molecular mechanism, identified in laboratory crosses, provided the first genetic evidence of a Dobzhansky–Muller incompatibility causing F1 hybrid sterility in vertebrates and has been considered a general model across strains and laboratories. Here, we use mice from natural populations and find that F1 hybrid sterility is polymorphic and asymmetric, with fertility phenotypes modulated by the direction of the cross. Although sterile males carried incompatible Prdm9 alleles, quantitative trait loci (QTL) mapping in backcross progeny revealed no significant associations with chromosome 17, where Prdm9 resides. Instead, sterility consistently mapped to X-linked loci, and the genomic position of sterility-associated QTL shifted between reciprocal backcrosses. These findings uncover a previously unrecognized mode of hybrid sterility in which X-linked incompatibilities act independently of Prdm9 , a mechanism we term Prdm9 -independent X-linked sterility (PIXLS). Our results extend the established Prdm9 / Mir465 model by demonstrating that hybrid sterility in house mice can arise through alternative genetic routes, highlighting the evolutionary diversity of reproductive barriers in their natural hybrid zone.
Local Maintenance and Genomic Diversity of Lymphocytic Choriomeningitis Virus in Natural Populations of House Mice in the Czech Republic Over a 24-Year Period Ivana Jezkova, Alena Fornůsková, Ľudovít Ďureje, Miloš Macholán, Jaroslav Piálek, et al. Zoonoses and Public Health, 2026 Lymphocytic choriomeningitis virus (LCMV) is a neglected rodent‐borne zoonotic virus primarily infecting house mice. The virus can be highly pathogenic, particularly in immunocompromised individuals and in congenital infections. LCMV is distributed worldwide but shows local clustering, probably due to the highly structured populations of its hosts and the vertical transmission of the pathogen. These factors should also promote long‐term virus persistence in wild populations, yet this aspect remains largely unexplored. To investigate this, we resampled a transect in the western Czech Republic that was primarily studied more than a decade ago. Additionally, we analyzed a sample collection from Buškovice, a locality where LCMV was first detected in 2008, to trace virus presence back to the year 2000. Positive samples underwent whole‐genome characterisation to assess the virus's genetic structure over space and time. We detected intermittent presence over 24 years in a geographically limited area, where LCMV was already present in 2000 and remained detectable in 2023. Phylogenetic analysis showed no clear spatio‐temporal clustering, suggesting that virus persistence in Buškovice is a dynamic process involving mouse dispersal between neighbouring villages. Given LCMV's zoonotic potential and house mouse synanthropy, these findings highlight the need for continuous monitoring in the region.
Mouse X-linked microRNA cluster regulates the meiotic checkpoint and Prdm9-driven hybrid sterility in a copy number–dependent manner Petr Jansa, Giordano Tanieli, Kim Vucinic, Diana Lustyk, Karel Fusek, et al. Proceedings of the National Academy of Sciences of the United States of America, 2025 One of the reproductive barriers between diverging populations during formation of a new species is the sterility of their hybrids. The Prdm9- driven hybrid male sterility of Mus musculus musculus × Mus musculus domesticus hybrids depends on the interaction between PRDM9, a histone methyltransferase that determines the positions of meiotic recombination hotspots, and an as yet unknown X-linked genetic factor within the Hybrid sterility X2 ( Hstx2 ) locus. Here, we report that the Mir465 microRNA (miRNA) gene cluster is the predicted Hstx2 hybrid sterility factor. We show that removal of the Mir465 genes restores the fertility of sterile hybrids and improves meiotic synapsis of homologous chromosomes. Mir465 knockout also restores spermatogenesis in sterile chromosomal translocation carriers, demonstrating that Mir465 acts as a meiotic checkpoint that can be activated independently of Prdm9 intersubspecific incompatibility. Furthermore, the Mir465 knockout increases the global recombination rate in hybrids and in parental Mus m. domesticus mice. This demonstrates that Mir465 is responsible for the phenotypes of the two overlapping genetic loci, the Hstx2 engaged in fertility of hybrids and the Meiotic recombination 1 ( Meir1 ) controlling the recombination rate. The finding of enlarged Mir465 clusters in all European Mus m. musculus samples tested and the identification of differentially expressed targets suggest that the reproductive barrier between the two subspecies is sensitive to copy number variation of Mir465 genes. Together, the underdominant interaction between Prdm9 and Mir465 provides a rare example of Dobzhansky–Muller incompatibility in hybrids of closely related species, making it accessible for further analysis at the molecular level.
A reappraisal of mitochondrial DNA introgression in the Mus musculus musculus/Mus musculus domesticus hybrid zone suggests ancient North-European associations between mice and humans Miloš Macholán, Stuart J E Baird, Alena Fornůsková, Ľudovít Ďureje, Jörg P Burgstaller, et al. Zoological Journal of the Linnean Society, 2024 The house mouse is the best-studied mammal species after humans, yet our understanding of its evolutionary history remains incomplete. Here, we focused on the colonisation of Europe by two subspecies and formation of a hybrid zone between them. We carried out a large-scale study of ~7000 mice sampled across an area embracing an ~900 km long portion of the zone, supplemented with cytochrome b and D-loop sequencing of ~1200 individuals collected worldwide. We demonstrate that the course of the mtDNA contact front is intricate and highly discordant with the consensus front for autosomal and X-linked markers, suggesting that local snapshots of mtDNA introgression may be misleading when treated in isolation. While multiple unrelated M. m. domesticus haplotypes occur in the zone area, the diversity of M. m. musculus haplotypes is limited. Moreover, we uncovered a vast region of domesticus introgression into musculus territory in northern areas and showed this introgression is unlikely to be driven by positive selection. We consider two previously published hypotheses explaining this phenomenon and put forth an alternative scenario assuming associations between mice and humans in northern Europe during the Nordic Bronze Age and subsequent zone movement associated with the expansion of Balto-Slavic peoples.
The strength of gut microbiota transfer along social networks and genealogical lineages in the house mouse Barbora Bendová, Barbora Vošlajerová Bímová, Dagmar Čížková, Kristina Daniszová, Ľudovít Ďureje, et al. FEMS Microbiology Ecology, 2024 The gut microbiota of vertebrates is acquired from the environment and other individuals, including parents and unrelated conspecifics. In the laboratory mouse, a key animal model, inter-individual interactions are severely limited and its gut microbiota is abnormal. Surprisingly, our understanding of how inter-individual transmission impacts house mouse gut microbiota is solely derived from laboratory experiments. We investigated the effects of inter-individual transmission on gut microbiota in two subspecies of house mice (Mus musculus musculus and M. m. domesticus) raised in a semi-natural environment without social or mating restrictions. We assessed the correlation between microbiota composition (16S rRNA profiles), social contact intensity (microtransponder-based social networks), and mouse relatedness (microsatellite-based pedigrees). Inter-individual transmission had a greater impact on the lower gut (colon and cecum) than on the small intestine (ileum). In the lower gut, relatedness and social contact independently influenced microbiota similarity. Despite female-biased parental care, both parents exerted a similar influence on their offspring’s microbiota, diminishing with the offspring’s age in adulthood. Inter-individual transmission was more pronounced in M. m. domesticus, a subspecies, with a social and reproductive network divided into more closed modules. This suggests that the transmission magnitude depends on the social and genetic structure of the studied population.
Convergence of gut phage communities but not bacterial communities following wild mouse bacteriophage transplantation into captive house mice Dagmar Čížková, Pavel Payne, Anna Bryjová, Ľudovít Ďureje, Jaroslav Piálek, et al. Isme Journal, 2024 Bacteriophages are abundant components of vertebrate gut microbial communities, impacting bacteriome dynamics, evolution, and directly interacting with the superhost. However, knowledge about gut phageomes and their interaction with bacteriomes in vertebrates under natural conditions is limited to humans and non-human primates. Widely used specific-pathogen-free (SPF) mouse models of host-microbiota interactions have altered gut bacteriomes compared to wild mice, and data on phageomes from wild or other non-SPF mice are lacking. We demonstrate divergent gut phageomes and bacteriomes in wild and captive non-SPF mice, with wild mice phageomes exhibiting higher alpha-diversity and interindividual variability. In both groups, phageome and bacteriome structuring mirrored each other, correlating at the individual level. Re-analysis of previous data from phageomes of SPF mice revealed their enrichment in Suoliviridae crAss-like phages compared to our non-SPF mice. Disrupted bacteriomes in mouse models can be treated by transplanting healthy phageomes, but the effects of phageome transplants on healthy adult gut microbiota are still unknown. We show that experimental transplantation of phageomes from wild to captive mice did not cause major shifts in recipient phageomes. However, the convergence of recipient-to-donor phageomes confirmed that wild phages can integrate into recipient communities. The differences in the subset of integrated phages between the two recipient mouse strains illustrate the context-dependent effects of phage transplantation. The transplantation did not impact recipient gut bacteriomes. This resilience of healthy adult gut microbiomes to the intervention has implications for phage allotransplantation safety.
The effect of host admixture on wild house mouse gut microbiota is weak when accounting for spatial autocorrelation Dagmar Čížková, Lucie Schmiedová, Martin Kváč, Bohumil Sak, Miloš Macholán, et al. Molecular Ecology, 2024 The question of how interactions between the gut microbiome and vertebrate hosts contribute to host adaptation and speciation is one of the major problems in current evolutionary research. Using bacteriome and mycobiome metabarcoding, we examined how these two components of the gut microbiota vary with the degree of host admixture in secondary contact between two house mouse subspecies (Mus musculus musculus and M. m. domesticus). We used a large data set collected at two replicates of the hybrid zone and model‐based statistical analyses to ensure the robustness of our results. Assuming that the microbiota of wild hosts suffers from spatial autocorrelation, we directly compared the results of statistical models that were spatially naive with those that accounted for spatial autocorrelation. We showed that neglecting spatial autocorrelation can strongly affect the results and lead to misleading conclusions. The spatial analyses showed little difference between subspecies, both in microbiome composition and in individual bacterial lineages. Similarly, the degree of admixture had minimal effects on the gut bacteriome and mycobiome and was caused by changes in a few microbial lineages that correspond to the common symbionts of free‐living house mice. In contrast to previous studies, these data do not support the hypothesis that the microbiota plays an important role in host reproductive isolation in this particular model system.
Aberrant microbiomes are associated with increased antibiotic resistance gene load in hybrid mice Víctor Hugo Jarquín-Díaz, Susana Carolina Martins Ferreira, Alice Balard, Ľudovít Ďureje, Milos Macholán, et al. Isme Communications, 2024 Antibiotic resistance is a priority public health problem resulting from eco-evolutionary dynamics within microbial communities and their interaction at a mammalian host interface or geographical scale. The links between mammalian host genetics, bacterial gut community, and antimicrobial resistance gene (ARG) content must be better understood in natural populations inhabiting heterogeneous environments. Hybridization, the interbreeding of genetically divergent populations, influences different components of the gut microbial communities. However, its impact on bacterial traits such as antibiotic resistance is unknown. Here, we present that hybridization might shape bacterial communities and ARG occurrence. We used amplicon sequencing to study the gut microbiome and to predict ARG composition in natural populations of house mice (Mus musculus). We compared gastrointestinal bacterial and ARG diversity, composition, and abundance across a gradient of pure and hybrid genotypes in the European House Mouse Hybrid Zone. We observed an increased overall predicted richness of ARG in hybrid mice. We found bacteria–ARG interactions by their co-abundance and detected phenotypes of extreme abundances in hybrid mice at the level of specific bacterial taxa and ARGs, mainly multidrug resistance genes. Our work suggests that mammalian host genetic variation impacts the gut microbiome and chromosomal ARGs. However, it raises further questions on how the mammalian host genetics impact ARGs via microbiome dynamics or environmental covariates.
Variation in mouse chemical signals is genetically controlled and environmentally modulated Romana Stopková, Tereza Matějková, Alica Dodoková, Pavel Talacko, Petr Zacek, et al. Scientific Reports, 2023 In most mammals and particularly in mice, chemical communication relies on the detection of ethologically relevant fitness-related cues from other individuals. In mice, urine is the primary source of these signals, so we employed proteomics and metabolomics to identify key components of chemical signalling. We show that there is a correspondence between urinary volatiles and proteins in the representation of genetic background, sex and environment in two house mouse subspecies Mus musculus musculus and M. m. domesticus. We found that environment has a strong influence upon proteomic and metabolomic variation and that volatile mixtures better represent males while females have surprisingly more sex-biased proteins. Using machine learning and combined-omics techniques, we identified mixtures of metabolites and proteins that are associated with biological features.
