The classical definition posits hybrid sterility as a phenomenon when two parental taxa each of which is fertile produce a hybrid that is sterile. The first hybrid sterility gene in vertebrates, Prdm9, coding for a histone methyltransferase, was identified in crosses between two laboratory mouse strains derived from Mus mus musculus and M. m. domesticus subspecies. The unique function of PRDM9 protein in the initiation of meiotic recombination led to the discovery of the basic molecular mechanism of hybrid sterility in laboratory crosses. However, the role of this protein as a component of reproductive barrier outside the laboratory model remained unclear. Here, we show that the Prdm9 allelic incompatibilities represent the primary cause of reduced fertility in intersubspecific hybrids between M. m. musculus and M. m. domesticus including 16 musculus and domesticus wild-derived strains. Disruption of fertility phenotypes correlated with the rate of failure of synapsis between homologous chromosomes in meiosis I and with early meiotic arrest. All phenotypes were restored to normal when the domesticus Prdm9dom2 allele was substituted with the Prdm9dom2H humanized variant. To conclude, our data show for the first time the male infertility of wild-derived musculus and domesticus subspecies F1 hybrids controlled by Prdm9 as the major hybrid sterility gene. The impairment of fertility surrogates, testes weight and sperm count, correlated with increasing difficulties of meiotic synapsis of homologous chromosomes and with meiotic arrest, which we suppose reflect the increasing asymmetry of PRDM9-dependent DNA double-strand breaks.

• Klíčová slova
• Prdm9 polymorphism, HORMAD2, meiotic chromosome synapsis, reproductive isolation, synaptonemal complex,
• MeSH
• fylogeografie MeSH
• genová introgrese * MeSH
• histonlysin-N-methyltransferasa genetika   MeSH
• infertilita genetika   MeSH
• meióza MeSH
• myši genetika   MeSH
• reprodukční izolace * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši genetika   MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• histonlysin-N-methyltransferasa MeSH
• prdm9 protein, mouse MeSH Prohlížeč

The widespread and locally massive introgression of Y chromosomes of the eastern house mouse (Mus musculus musculus) into the range of the western subspecies (M. m. domesticus) in Central Europe calls for an explanation of its underlying mechanisms. Given the paternal inheritance pattern, obvious candidates for traits mediating the introgression are characters associated with sperm quantity and quality. We can also expect traits such as size, aggression or the length of generation cycles to facilitate the spread. We have created two consomic strains carrying the non-recombining region of the Y chromosome of the opposite subspecies, allowing us to study introgression in both directions, something impossible in nature due to the unidirectionality of introgression. We analyzed several traits potentially related to male fitness. Transmission of the domesticus Y onto the musculus background had negative effects on all studied traits. Likewise, domesticus males possessing the musculus Y had, on average, smaller body and testes and lower sperm count than the parental strain. However, the same consomic males tended to produce less- dissociated sperm heads, to win more dyadic encounters, and to have shorter generation cycles than pure domesticus males. These data suggest that the domesticus Y is disadvantageous on the musculus background, while introgression in the opposite direction can confer a recognizable, though not always significant, selective advantage. Our results are thus congruent with the unidirectional musculus → domesticus Y chromosome introgression in Central Europe. In addition to some previous studies, they show this to be a multifaceted phenomenon demanding a multidisciplinary approach.

• MeSH
• agrese * MeSH
• chromozom Y * genetika   MeSH
• fenotyp MeSH
• myši genetika   MeSH
• spermie fyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši genetika   MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH

F1 hybrids between mouse inbred strains PWD and C57BL/6 represent the most thoroughly genetically defined model of hybrid sterility in vertebrates. Hybrid male sterility can be fully reconstituted from three components of this model, the Prdm9 gene, intersubspecific homeology of Mus musculus musculus and Mus musculus domesticus autosomes, and the X-linked Hstx2 locus. Hstx2 modulates the extent of Prdm9-dependent meiotic arrest and harbors two additional factors responsible for intersubspecific introgression-induced oligospermia (Hstx1) and meiotic recombination rate (Meir1). To facilitate positional cloning and to overcome the recombination suppression within the 4.3 Mb encompassing the Hstx2 locus, we designed Hstx2-CRISPR and SPO11/Cas9 transgenes aimed to induce DNA double-strand breaks specifically within the Hstx2 locus. The resulting recombinant reduced the Hstx2 locus to 2.70 Mb (chromosome X: 66.51-69.21 Mb). The newly defined Hstx2 locus still operates as the major X-linked factor of the F1 hybrid sterility, and controls meiotic chromosome synapsis and meiotic recombination rate. Despite extensive further crosses, the 2.70 Mb Hstx2 interval behaved as a recombination cold spot with reduced PRDM9-mediated H3K4me3 hotspots and absence of DMC1-defined DNA double-strand-break hotspots. To search for structural anomalies as a possible cause of recombination suppression, we used optical mapping and observed high incidence of subspecies-specific structural variants along the X chromosome, with a striking copy number polymorphism of the microRNA Mir465 cluster. This observation together with the absence of a strong sterility phenotype in Fmr1 neighbor (Fmr1nb) null mutants support the role of microRNA as a likely candidate for Hstx2.

• Klíčová slova
• Bionano optical mapping, Fmr1nb, Hybrid sterility X2, Prdm9, SPO11Cas9 transgene, Speciation,
• MeSH
• chromozom X genetika   MeSH
• histonlysin-N-methyltransferasa genetika   MeSH
• homologní rekombinace MeSH
• meióza MeSH
• mikro RNA genetika   MeSH
• modifikátorové geny * MeSH
• mužská infertilita genetika   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• polymorfismus genetický * 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
• mikro RNA MeSH
• prdm9 protein, mouse MeSH Prohlížeč

Hybrid zones between divergent populations sieve genomes into blocks that introgress across the zone, and blocks that do not, depending on selection between interacting genes. Consistent with Haldane's rule, the Y chromosome has been considered counterselected and hence not to introgress across the European house mouse hybrid zone. However, recent studies detected massive invasion of M. m. musculus Y chromosomes into M. m. domesticus territory. To understand mechanisms facilitating Y spread, we created 31 recombinant lines from eight wild-derived strains representing four localities within the two mouse subspecies. These lines were reciprocally crossed and resulting F1 hybrid males scored for five phenotypic traits associated with male fitness. Molecular analyses of 51 Y-linked SNPs attributed ~50% of genetic variation to differences between the subspecies and 8% to differentiation within both taxa. A striking proportion, 21% (frequencies of sperm head abnormalities) and 42% (frequencies of sperm tail dissociations), of phenotypic variation was explained by geographic Y chromosome variants. Our crossing design allowed this explanatory power to be examined across a hierarchical scale from subspecific to local intrastrain effects. We found that divergence and variation were expressed diversely in different phenotypic traits and varied across the whole hierarchical scale. This finding adds another dimension of complexity to studies of Y introgression not only across the house mouse hybrid zone but potentially also in other contact zones.

• Klíčová slova
• Mus musculus domesticus, Mus musculus musculus, Y‐associated effects, phenotype variation, sperm quality, wild‐derived strain,
• Publikační typ
• časopisecké články MeSH

Reproductive isolation is crucial for the process of speciation to progress. Sex chromosomes have been assigned a key role in driving reproductive isolation but empirical evidence from natural population processes has been restricted to organisms with degenerated sex chromosomes such as mammals and birds. Here we report restricted introgression at sex-linked compared to autosomal markers in a hybrid zone between two incipient species of European tree frog, Hyla arborea and H. orientalis, whose homologous X and Y sex chromosomes are undifferentiated. This large X-effect cannot result from the dominance or faster-X aspects of Haldane's rule, which are specific to degenerated sex chromosomes, but rather supports a role for faster-heterogametic-sex or faster-male evolutionary processes. Our data suggest a prominent contribution of undifferentiated sex chromosomes to speciation.

• MeSH
• chromozom X genetika   MeSH
• chromozom Y genetika   MeSH
• Ranidae MeSH
• sexuální diferenciace genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Being subject to intense post-copulatory selection, sperm size is a principal determining component of male fitness. Although previous studies have presented comparative sperm size data at higher taxonomic levels, information on the evolution of sperm size within species is generally lacking. Here, we studied two house mouse subspecies, Mus musculus musculus and Mus musculus domesticus, which undergo incipient speciation. We measured four sperm dimensions from cauda epididymis smears of 28 wild-caught mice of both subspecies. As inbred mouse strains are frequently used as proxies for exploring evolutionary processes, we further studied four wild-derived inbred strains from each subspecies. The subspecies differed significantly in terms of sperm head length and midpiece length, and these differences were consistent for wild mice and wild-derived strains pooled over genomes. When the inbred strains were analyzed individually, however, their strain-specific values were in some cases significantly shifted from subspecies-specific values derived from wild mice. We conclude that: (1) the size of sperm components differ in the two house mouse subspecies studied, and that (2) wild-derived strains reflect this natural polymorphism, serving as a potential tool to identify the genetic variation driving these evolutionary processes. Nevertheless, we suggest that more strains should be used in future experiments to account for natural variation and to avoid confounding results due to reduced variability and/or founder effect in the individual strains.

• MeSH
• genetická variace MeSH
• inbrední kmeny myší MeSH
• myši MeSH
• spermie cytologie   MeSH
• vznik druhů (genetika) * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Detailed investigation of variation in genes involved in pathogen recognition is crucial for understanding co-evolutionary processes between parasites and their hosts. Triggering immediate innate response to invading microbes, Toll-like receptors (TLRs) belong presently among the best-studied receptors of vertebrate immunity. TLRs exhibit remarkable interspecific variation and also intraspecific polymorphism is well documented. In humans and laboratory mice, several studies have recently shown that single amino acid substitution may significantly alter receptor function. Unfortunately, data concerning polymorphism in free-living species are still surprisingly scarce. In this study, we analyzed the polymorphism of Toll-like receptor 4 (Tlr4) over the Palearctic range of house mouse (Mus musculus). Our results reveal contrasting evolutionary patterns between the two recently (0.5 million years ago) diverged house mouse subspecies: M. m. domesticus (Mmd) and M. m. musculus (Mmm). Comparison with cytochrome b indicates strong directional selection in Mmd Tlr4. Throughout the whole Mmd western Palaearctic region, a single variant of the ligand-binding region is spread, encoded mainly by one dominant haplotype (71% of Mmd). In contrast, Tlr4 in Mmm is much more polymorphic with several haplotypes at intermediate frequencies. Moreover, we also found clear signals of recombination between two principal haplogroups in Mmm, and we identified eight sites under positive selection in our dataset. Our results suggest that observed differences in Tlr4 diversity may be attributed to contrasting parasite-mediated selection acting in the two subspecies.

• Klíčová slova
• Adaptive evolution, MAMPs, Mus musculus, arms race, directional selection, host–pathogen interaction, parasite-mediated selection, pattern-recognition receptors,
• Publikační typ
• časopisecké články MeSH

Hybrid sterility (HS) belongs to reproductive isolation barriers that safeguard the integrity of species in statu nascendi. Although hybrid sterility occurs almost universally among animal and plant species, most of our current knowledge comes from the classical genetic studies on Drosophila interspecific crosses or introgressions. With the house mouse subspecies Mus m. musculus and Mus m. domesticus as a model, new research tools have become available for studies of the molecular mechanisms and genetic networks underlying HS. Here we used QTL analysis and intersubspecific chromosome substitution strains to identify a 4.7 Mb critical region on Chromosome X (Chr X) harboring the Hstx2 HS locus, which causes asymmetrical spermatogenic arrest in reciprocal intersubspecific F1 hybrids. Subsequently, we mapped autosomal loci on Chrs 3, 9 and 13 that can abolish this asymmetry. Combination of immunofluorescent visualization of the proteins of synaptonemal complexes with whole-chromosome DNA FISH on pachytene spreads revealed that heterosubspecific, unlike consubspecific, homologous chromosomes are predisposed to asynapsis in F1 hybrid male and female meiosis. The asynapsis is under the trans- control of Hstx2 and Hst1/Prdm9 hybrid sterility genes in pachynemas of male but not female hybrids. The finding concurred with the fertility of intersubpecific F1 hybrid females homozygous for the Hstx2(Mmm) allele and resolved the apparent conflict with the dominance theory of Haldane's rule. We propose that meiotic asynapsis in intersubspecific hybrids is a consequence of cis-acting mismatch between homologous chromosomes modulated by the trans-acting Hstx2 and Prdm9 hybrid male sterility genes.

• MeSH
• chromozom X genetika   MeSH
• genetické lokusy genetika   MeSH
• histonlysin-N-methyltransferasa genetika   MeSH
• hybridizace genetická MeSH
• lidé MeSH
• lokus kvantitativního znaku genetika   MeSH
• meióza MeSH
• mužská infertilita genetika   MeSH
• myši MeSH
• párování chromozomů genetika   MeSH
• reprodukční izolace MeSH
• synaptonemální komplex genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• histonlysin-N-methyltransferasa MeSH
• prdm9 protein, mouse MeSH Prohlížeč

Two house mouse subspecies occur in Europe, eastern and northern Mus musculus musculus (Mmm) and western and southern Mus musculus domesticus (Mmd). A secondary hybrid zone occurs where their ranges meet, running from Scandinavia to the Black Sea. In this paper, we tested a hypothesis that the apicomplexan protozoan species Cryptosporidium tyzzeri has coevolved with the house mouse. More specifically, we assessed to what extent the evolution of this parasite mirrors divergence of the two subspecies. In order to test this hypothesis, we analysed sequence variation at five genes (ssrRNA, Cryptosporidium oocyst wall protein (COWP), thrombospondin-related adhesive protein of Cryptosporidium 1 (TRAP-C1), actin and gp60) in C. tyzzeri isolates from Mmd and Mmm sampled along a transect across the hybrid zone from the Czech Republic to Germany. Mmd samples were supplemented with mice from New Zealand. We found two distinct isolates of C. tyzzeri, each occurring exclusively in one of the mouse subspecies (C. tyzzeri-Mmm and C. tyzzeri-Mmd). In addition to genetic differentiation, oocysts of the C. tyzzeri-Mmd subtype (mean: 4.24×3.69μm) were significantly smaller than oocysts of C. tyzzeri-Mmm (mean: 4.49×3.90 μm). Mmm and Mmd were susceptible to experimental infection with both C. tyzzeri subtypes; however, the subtypes were not infective for the rodent species Meriones unguiculatus, Mastomys coucha, Apodemus flavicollis or Cavia porcellus. Overall, our results support the hypothesis that C. tyzzeri is coevolving with Mmm and Mmd.

• Klíčová slova
• Coevolution, Cryptosporidium tyzzeri, House mouse, Hybrid zone, Mus musculus domesticus, Mus musculus musculus,
• MeSH
• biologická evoluce * MeSH
• Cryptosporidium klasifikace   genetika   izolace a purifikace   MeSH
• fylogeneze MeSH
• genetická variace MeSH
• genotyp MeSH
• kryptosporidióza veterinární   MeSH
• molekulární sekvence - údaje MeSH
• myši MeSH
• nemoci hlodavců parazitologie   MeSH
• protozoální proteiny genetika   MeSH
• RNA ribozomální 18S genetika   MeSH
• sekvenční analýza DNA MeSH
• shluková analýza MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Česká republika MeSH
• Německo MeSH
• Názvy látek
• protozoální proteiny MeSH
• RNA ribozomální 18S MeSH

The house mouse hybrid zone (HMHZ) is a species barrier thought to be maintained by a balance between dispersal and natural selection against hybrids. While the HMHZ is characterized by frequency discontinuities for some sex chromosome markers, there is an unexpected large-scale regional introgression of a Y chromosome across the barrier, in defiance of Haldane's rule. Recent work suggests that a major force maintaining the species barrier acts through sperm traits. Here, we test whether the Y chromosome penetration of the species barrier acts through sperm traits by assessing sperm characteristics of wild-caught males directly in a field laboratory set up in a Y introgression region of the HMHZ, later calculating the hybrid index of each male using 1401 diagnostic single nucleotide polymorphisms (SNPs). We found that both sperm count (SC) and sperm velocity were significantly reduced across the natural spectrum of hybrids. However, SC was more than rescued in the presence of the invading Y. Our results imply an asymmetric advantage for Y chromosome introgression consistent with the observed large-scale introgression. We suggest that selection on sperm-related traits probably explains a large component of patterns observed in the natural hybrid zone, including the Y chromosome penetration.

• MeSH
• chromozom Y * MeSH
• druhová specificita MeSH
• fenotyp MeSH
• hybridizace genetická * MeSH
• jednonukleotidový polymorfismus MeSH
• modely genetické MeSH
• myši fyziologie   MeSH
• selekce (genetika) MeSH
• spermie fyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši fyziologie   MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH