The house mouse, Mus musculus, is a widely used animal model in biomedical research, with classical laboratory strains (CLS) being the most frequently employed. However, the limited genetic variability in CLS hinders their applicability in evolutionary studies. Wild-derived strains (WDS), on the other hand, provide a suitable resource for such investigations. This study quantifies genetic and phenotypic data of 101 WDS representing 5 species, 3 subspecies, and 8 natural Y consomic strains and compares them with CLS. Genetic variability was estimated using whole mtDNA sequences, the Prdm9 gene, and copy number variation at two sex chromosome-linked genes. WDS exhibit a large natural variation with up to 2173 polymorphic sites in mitogenomes, whereas CLS display 92 sites. Moreover, while CLS have two Prdm9 alleles, WDS harbour 46 different alleles. Although CLS resemble M. m. domesticus and M. m. musculus WDS, they differ from them in 10 and 14 out of 16 phenotypic traits, respectively. The results suggest that WDS can be a useful tool in evolutionary and biomedical studies with great potential for medical applications.

• MeSH
• alely MeSH
• divoká zvířata genetika   MeSH
• druhová specificita MeSH
• fenotyp MeSH
• genetická variace * MeSH
• histonlysin-N-methyltransferasa genetika   MeSH
• mitochondriální DNA genetika   MeSH
• myši * genetika   MeSH
• variabilita počtu kopií segmentů DNA MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši * genetika   MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• histonlysin-N-methyltransferasa MeSH
• mitochondriální DNA MeSH
• prdm9 protein, mouse MeSH Prohlížeč

Hybrid sterility is a reproductive isolation barrier between diverging taxa securing the early steps of speciation. Hybrid sterility is ubiquitous in the animal and plant kingdoms, but its genetic control is poorly understood. In our previous studies, we have uncovered the sterility of hybrids between musculus and domesticus subspecies of the house mouse, which is controlled by the Prdm9 gene, the X-linked Hstx2 locus, and subspecific heterozygosity for genetic background. To further investigate this form of genic-driven chromosomal sterility, we constructed a simplified hybrid sterility model within the genome of the domesticus subspecies by swapping domesticus autosomes with their homologous partners from the musculus subspecies. We show that the "sterility" allelic combination of Prdm9 and Hstx2 can be activated by a musculus/domesticus heterozygosity of as few as two autosomes, Chromosome 17 (Chr 17) and Chr 18 and is further enhanced when another heterosubspecific autosomal pair is present, whereas it has no effect on meiotic progression in the pure domesticus genome. In addition, we identify a new X-linked hybrid sterility locus, Hstx3, at the centromeric end of Chr X, which modulates the incompatibility between Prdm9 and Hstx2. These results further support our concept of chromosomal hybrid sterility based on evolutionarily accumulated divergence between homologous sequences. Based on these and previous results, we believe that future studies should include more information on the mutual recognition of homologous chromosomes at or before the first meiotic prophase in interspecific hybrids, as this may serve as a general reproductive isolation checkpoint in mice and other species.

• Klíčová slova
• Mus musculus, chromosome, genomes, hybrid, meiosis, speciation,
• MeSH
• genom MeSH
• histonlysin-N-methyltransferasa * genetika   MeSH
• hybridizace genetická * MeSH
• infertilita genetika   MeSH
• myši MeSH
• reprodukční izolace MeSH
• vznik druhů (genetika) MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• histonlysin-N-methyltransferasa * MeSH
• prdm9 protein, mouse MeSH Prohlížeč

PRDM9-mediated reproductive isolation was first described in the progeny of Mus musculus musculus (MUS) PWD/Ph and Mus musculus domesticus (DOM) C57BL/6J inbred strains. These male F1 hybrids fail to complete chromosome synapsis and arrest meiosis at prophase I, due to incompatibilities between the Prdm9 gene and hybrid sterility locus Hstx2. We identified 14 alleles of Prdm9 in exon 12, encoding the DNA-binding domain of the PRDM9 protein in outcrossed wild mouse populations from Europe, Asia, and the Middle East, 8 of which are novel. The same allele was found in all mice bearing introgressed t-haplotypes encompassing Prdm9. We asked whether 7 novel Prdm9 alleles in MUS populations and the t-haplotype allele in 1 MUS and 3 DOM populations induce Prdm9-mediated reproductive isolation. The results show that only combinations of the dom2 allele of DOM origin and the MUS msc1 allele ensure complete infertility of intersubspecific hybrids in outcrossed wild populations and inbred mouse strains examined so far. The results further indicate that MUS mice may share the erasure of PRDM9msc1 binding motifs in populations with different Prdm9 alleles, which implies that erased PRDM9 binding motifs may be uncoupled from their corresponding Prdm9 alleles at the population level. Our data corroborate the model of Prdm9-mediated hybrid sterility beyond inbred strains of mice and suggest that sterility alleles of Prdm9 may be rare.

• Klíčová slova
• Hstx2, Mus musculus, Prdm9, t-haplotype, asynapsis, fertility, reproductive isolation,
• MeSH
• exony MeSH
• fenotyp MeSH
• histonlysin-N-methyltransferasa genetika   metabolismus   MeSH
• infertilita * genetika   MeSH
• lidé MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• zinek MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• histonlysin-N-methyltransferasa MeSH
• PRDM9 protein, human MeSH Prohlížeč
• prdm9 protein, mouse MeSH Prohlížeč
• zinek MeSH

Intrinsic postzygotic isolation typically appears as reduced viability or fertility of interspecific hybrids caused by genetic incompatibilities between diverged parental genomes. Dobzhansky-Muller interactions among individual genes, and chromosomal rearrangements causing problems with chromosome synapsis and recombination in meiosis, have both long been considered as major mechanisms behind intrinsic postzygotic isolation. Recent research has, however, suggested that the genetic basis of intrinsic postzygotic isolation can be more complex and involves, for example, overall divergence of the DNA sequence or epigenetic changes. Here, we review the mechanisms of intrinsic postzygotic isolation from genic, chromosomal, genomic, and epigenetic perspectives across diverse taxa. We provide empirical evidence for these mechanisms, discuss their importance in the speciation process, and highlight questions that remain unanswered.

• MeSH
• chromozomy * MeSH
• genom MeSH
• genomika * MeSH
• hybridizace genetická MeSH
• reprodukční izolace MeSH
• vznik druhů (genetika) MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Hybrid sterility (HS) is an early postzygotic reproductive isolation mechanism observed in all sexually reproducing species. Infertility of hybrids prevents gene flow between incipient species and leads to speciation. While Drosophila studies have focused almost exclusively on the genic control of HS, two other model species, Mus musculus and budding yeast, provided the first experimental evidence of hybrid sterility governed by the nongenic effects of DNA sequence divergence. Here, we propose that the nongenic effect of increasing DNA divergence between closely related species may impair mutual recognition of homologous chromosomes and disrupt their synapsis. Unsynapsed or mispaired homologs can induce early meiotic arrest, or their random segregation can cause aneuploidy of spermatids and sperm cells. Impaired recognition of homologs may thus act as a universal chromosomal checkpoint contributing to the complexity of genetic control of HS. Chromosomal HS controlled by the Prdm9 gene in mice and HS driven by the mismatch repair machinery in yeast are currently the most advanced examples of chromosomal homology search-based HS. More focus on the cellular and molecular phenotypes of meiosis will be needed to further validate the role of homolog recognition in hybrid sterility and speciation.

• Klíčová slova
• Prdm9, antirecombination, chromosomal sterility, meiotic pairing, reproductive isolation, speciation,
• MeSH
• chromozomy MeSH
• histonlysin-N-methyltransferasa genetika   MeSH
• hybridizace genetická MeSH
• infertilita * genetika   MeSH
• lidé MeSH
• meióza MeSH
• mužská infertilita * genetika   MeSH
• myši MeSH
• Saccharomyces cerevisiae genetika   MeSH
• semena rostlinná MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• histonlysin-N-methyltransferasa MeSH
• PRDM9 protein, human MeSH Prohlížeč
• prdm9 protein, mouse MeSH Prohlížeč

Aneuploidy (abnormal chromosome number) accompanies reduced ovarian function in humans and mice, but the reasons behind this concomitance remain underexplored. Some variants in the human gene encoding histone-3-lysine-4,36-trimethyltransferase PRDM9 are associated with aneuploidy, and other variants with ovarian function reduced by premature ovarian failure (POF), but no link between POF and aneuploidy has been revealed. SHR/OlaIpcv rat females lacking PRDM9 manifest POF-a reduced follicle number, litter size, and reproductive age. Here, we explored this model to test how POF relates to oocyte euploidy. The mutant rat females displayed increased oocyte aneuploidy and embryonic death of their offspring compared to controls. Because rat PRDM9 positions meiotic DNA breaks, we investigated the repair of these breaks. Fertile control rodents carry pachytene oocytes with synapsed homologous chromosomes and repaired breaks, while sterile Prdm9-deficient mice carry pachytene-like oocytes with many persisting breaks and asynapsed chromosomes. However, most PRDM9-lacking rat oocytes displayed a few persisting breaks and non-homologous synapsis (NHS). HORMAD2 protein serves as a barrier to sister-chromatid repair and a signal for the synapsis and DNA repair checkpoints. NHS but not asynapsis was associated with HORMAD2 levels similar to the levels on rat pachytene chromosomes with homologous synapsis. NHS was accompanied by crossing-over decreased below the minimum that is essential for euploidy. We argue that the increased mutant rat aneuploidy is due to NHS, which allows some oocytes to pass meiotic checkpoints without one crossing-over per chromosomal pair, leading to segregation errors, and thereby NHS links POF to aneuploidy.

• MeSH
• aneuploidie * MeSH
• chromozomy MeSH
• histonlysin-N-methyltransferasa * genetika   metabolismus   MeSH
• krysa rodu Rattus MeSH
• meióza * genetika   MeSH
• oocyty metabolismus   MeSH
• párování chromozomů * genetika   MeSH
• potkani inbrední SHR MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• histonlysin-N-methyltransferasa * MeSH

Hybrid sterility contributes to speciation by preventing gene flow between related taxa. Prdm9, the first and only hybrid male sterility gene known in vertebrates, predetermines the sites of recombination between homologous chromosomes and their synapsis in early meiotic prophase. The asymmetric binding of PRDM9 to heterosubspecific homologs of Mus musculus musculus × Mus musculus domesticus F1 hybrids and increase of PRDM9-independent DNA double-strand break hotspots results indificult- to- repair double-strand breaks, incomplete synapsis of homologous chromosomes, and meiotic arrest at the first meiotic prophase. Here, we show that Prdm9 behaves as a major hybrid male sterility gene in mice outside the Mus musculus musculus × Mus musculus domesticus F1 hybrids, in the genomes composed of Mus musculus castaneus and Mus musculus musculus chromosomes segregating on the Mus musculus domesticus background. The Prdm9cst/dom2 (castaneus/domesticus) allelic combination secures meiotic synapsis, testes weight, and sperm count within physiological limits, while the Prdm9msc1/dom2 (musculus/domesticus) males show a range of fertility impairment. Out of 5 quantitative trait loci contributing to the Prdm9msc1/dom2-related infertility, 4 control either meiotic synapsis or fertility phenotypes and 1 controls both, synapsis, and fertility. Whole-genome genotyping of individual chromosomes showed preferential involvement of nonrecombinant musculus chromosomes in asynapsis in accordance with the chromosomal character of hybrid male sterility. Moreover, we show that the overall asynapsis rate can be estimated solely from the genotype of individual males by scoring the effect of nonrecombinant musculus chromosomes. Prdm9-controlled hybrid male sterility represents an example of genetic architecture of hybrid male sterility consisting of genic and chromosomal components.

• Klíčová slova
• HORMAD2, SYCP3, homologous synapsis, meiosis, spermatogenesis, synaptonemal complex,
• MeSH
• chromozomy MeSH
• histonlysin-N-methyltransferasa genetika   metabolismus   MeSH
• meióza * genetika   MeSH
• mužská infertilita * genetika   MeSH
• myši MeSH
• sperma metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• histonlysin-N-methyltransferasa MeSH
• prdm9 protein, mouse MeSH Prohlížeč