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Sterility or subfertility of male hybrid offspring is commonly observed. This phenomenon contributes to reproductive barriers between the parental populations, an early step in the process of speciation. One frequent cause of such infertility is a failure of proper chromosome pairing during male meiosis. In subspecies of the house mouse, the likelihood of successful chromosome synapsis is improved by the binding of the histone methyltransferase PRDM9 to both chromosome homologs at matching positions. Using genetic manipulation, we altered PRDM9 binding to occur more often at matched sites, and find that chromosome pairing defects can be rescued, not only in an intersubspecific cross, but also between distinct species. Using different engineered variants, we demonstrate a quantitative link between the degree of matched homolog binding, chromosome synapsis, and rescue of fertility in hybrids between Mus musculus and Mus spretus. The resulting partial restoration of fertility reveals additional mechanisms at play that act to lock-in the reproductive isolation between these two species.

Genic copy number differences can have phenotypic consequences, but so far this has not been studied in detail in natural populations. Here, we analysed the natu-ral variation of two families of tandemly repeated regulatory small nucleolar RNAs (SNORD115 and SNORD116) in the house mouse (Mus musculus). They are encoded within the Prader-Willi Syndrome gene region, known to be involved in behavioural, metabolic, and osteogenic functions in mammals. We determined that the copy num-bers of these SNORD RNAs show substantial natural variation, both in wild-derived mice as well as in an inbred mouse strain (C57BL/6J). We show that copy number dif-ferences are subject to change across generations, making them highly variable and resulting in individual differences. In transcriptome data from brain samples, we found SNORD copy- number correlated regulation of possible target genes, including Htr2c, a predicted target gene of SNORD115, as well as Ankrd11, a predicted target gene of SNORD116. Ankrd11 is a chromatin regulator, which has previously been implicated in regulating the development of the skull. Based on morphometric shape analysis of the skulls of individual mice of the inbred strain, we show that shape measures correlate with SNORD116 copy numbers in the respective individuals. Our results suggest that the variable dosage of regulatory RNAs can lead to phenotypic variation between individuals that would typically have been ascribed to environmentally induced varia-tion, while it is actually encoded in individual differences of copy numbers of regula-tory molecules.

After the vkorc1 gene was first identified, changes occurring in the gene have been considered one of the main reasons of reduced susceptibility of house mice to anticoagulants. A no-choice feeding...

Hybrid male sterility (HMS) contributes to reproductive isolation commonly observed among house mouse (Mus musculus) subspecies, both in the wild and in laboratory crosses. Incompatibilities involving specific Prdm9 alleles and certain Chromosome (Chr) X genotypes are known determinants of fertility and HMS, and previous work in the field has demonstrated that genetic background modifies these two major loci. We constructed hybrids that have identical genotypes at Prdm9 and identical X chromosomes, but differ widely across the rest of the genome. In each case, we crossed female PWK/PhJ mice representative of the M. m. musculus subspecies to males from a classical inbred strain representative of M. m. domesticus: 129S1/SvImJ, A/J, C57BL/6J, or DBA/2J. We detected three distinct trajectories of fertility among the hybrids using breeding experiments. The PWK129S1 males were always infertile. PWKDBA2 males were fertile, despite their genotypes at the major HMS loci. We also observed age-dependent changes in fertility parameters across multiple genetic backgrounds. The PWKB6 and PWKAJ males were always infertile before 15 weeks and after 35 weeks, yet some PWKB6 and PWKAJ males were fertile between fifteen and 35 weeks. This observation could resolve previous contradictory reports about the fertility of PWKB6. Taken together, these results point to multiple segregating HMS modifier alleles, some of which have age-related modes of action. The ultimate identification of these alleles and their age-related mechanisms will advance understanding both of the genetic architecture of HMS and of how reproductive barriers are maintained between house mouse subspecies.

Background We conducted a vitamin K epoxide reductase subcomponent 1 (Vkorc1)-based nonsynonymous Single Nucleotide Polymorphism (nsSNP) screen with focus on the house mouse (Mus musculus domesticus), but that also considered the Norway rat (Rattus norvegicus) and roof rat (R. rattus) in the USA. Results We detected six Vkorc1 nsSNPs underlying the amino-acid polymorphisms Ala21Thr, Trp59Leu, Ile104Val, Val118Leu, Leu128Ser and Tyr139Cys in house mice (average coverage/SNP; n = 182 individuals), two nsSNPs underlying Arg35Pro and Gly46Ser in the Norway rat (n = 93), with the notable absence of Tyr139Cys (n = 179), and one nsSNP underlying Tyr25Phe in the roof rat (n = 27). Inferred resistance frequency is 29.1% for mice (variability of states 0-98.8%), 6.5% (0-33.3%) for the Norway rat, and 39.3% (0-52.6%) for the roof rat based on Tyr25Phe frequencies. Conclusions Resistance detected in the USA in the 1980s likely was the consequence of Vkorc1 mutations in mice (Leu128Ser and Tyr139Cys), Norway rats (Arg35Pro) and roof rats (Tyr25Phe). Patterns of variant sharing between the USA and Europe indicate the importance of convergent evolution and gene flow in spreading resistance. The spread of nsSNPs in mice between continents appears to have been more effective than in Norway rats. We hypothesize that Arg35Pro may have originated in Norway rats in the USA, whereas Tyr139Cys variants originated in Europe. Tyr25Phe is the likely cause for resistance in roof rats. Further genetic testing in the USA is required to close sampling gaps, and population genomic data are needed to study the origin and spread of this adaptive trait.

Island populations repeatedly evolve extreme body sizes, but the genomic basis of this pattern remains largely unknown. To understand how organisms on islands evolve gigantism, we compared genome-wide patterns of gene expression in Gough Island mice, the largest wild house mice in the world, and mainland mice from the WSB/EiJ wild-derived inbred strain. We used RNA-seq to quantify differential gene expression in three key metabolic organs: gonadal adipose depot, hypothalamus, and liver. Between 4,000 and 8,800 genes were significantly differentially expressed across the evaluated organs, representing between 20% and 50% of detected transcripts, with 20% or more of differentially expressed transcripts in each organ exhibiting expression fold changes of at least 2×. A minimum of 73 candidate genes for extreme size evolution, including Irs1 and Lrp1, were identified by considering differential expression jointly with other data sets: 1) genomic positions of published quantitative trait loci for body weight and growth rate, 2) whole-genome sequencing of 16 wild-caught Gough Island mice that revealed fixed single-nucleotide differences between the strains, and 3) publicly available tissue-specific regulatory elements. Additionally, patterns of differential expression across three time points in the liver revealed that Arid5b potentially regulates hundreds of genes. Functional enrichment analyses pointed to cell cycling, mitochondrial function, signaling pathways, inflammatory response, and nutrient metabolism as potential causes of weight accumulation in Gough Island mice. Collectively, our results indicate that extensive gene regulatory evolution in metabolic organs accompanied the rapid evolution of gigantism during the short time house mice have inhabited Gough Island.

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.

Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles—including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.

Meiotic recombination affects fertility, shuffles genomes, and modulates the effectiveness of natural selection. Despite conservation of the recombination pathway, the rate of recombination varies among individuals and along chromosomes. Recombination rate also differs among cells from the same organism, but this form of variation has received less attention. To identify patterns that characterize intercellular variation in the genome-wide recombination rate, we counted foci of the MLH1 recombination-associated protein in oocytes and spermatocytes from a panel of wild-derived inbred strains of house mice. Females show higher intercellular variation in MLH1 focus count than males from the same inbred strains. This pattern is consistent across strains from multiple subspecies, including 2 strains in which the average MLH1 focus count is higher in males. The sex difference in genome-wide recombination rate we report suggests that selection targeting recombination rate will be more efficient in males than in females.

Positive selection and purifying selection reduce levels of variation at linked neutral loci. One consequence of these processes is that the amount of neutral diversity and the meiotic recombination rate are predicted to be positively correlated across the genome—a prediction met in some species but not others. To better document the prevalence of selection at linked sites, we used new and published whole-genome sequences to survey nucleotide variation in population samples of the western European house mouse (Mus musculus domesticus) from Germany, France, and Gough Island, a remote volcanic island in the south Atlantic. Correlations between sequence variation and recombination rates estimated independently from dense linkage maps were consistently very weak (ρ ≤ 0.06), though they exceeded conventional significance thresholds. This pattern persisted in comparisons between genomic regions with the highest and lowest recombination rates, as well as in models incorporating the density of transcribed sites, the density of CpG dinucleotides, and divergence between mouse and rat as covariates. We conclude that natural selection affects linked neutral variation in a restricted manner in the western European house mouse.

To clarify genetic differences between subspecies of the house mouse Mus musculus, their distribution, and hybridization, we first conducted a comparative analysis of variability of nucleotide sequences of fragments of the nuclear gene Brca1, exon 11 (2331 bp), and mitochondrial gene Cox1 (1260 bp) in 40 house mice from West and East Europe, Transcaucasia, Siberia, and Central and South Asia. Brca1 genotypes were divided into five main groups, which differed in a number of fixed substitutions. Genotypes of each group are characteristic for the certain geographical region and the following subspecies: M. m. musculus, M. m. domesticus, M. m. castaneus, and M. m. wagneri together with M. m. gansuensis; a fifth group corresponds to an unidentified subspecies or a distinct genetic form of M. musculus from India (Sikkim State). Besides the homozygous specimens, we revealed mice, which were heterozygous for all diagnostic loci simultaneously; these specimens were determined as hybrid. Hybrid mice were mainly found in the zones of contact of subspecies, but in some cases, quite far from one of the parent subspecies (possibly, due to transportation). In two hybrid mice (from Bakhtiari Province of Iran and Transbaikalia of Russia), unique Brca1 haplotypes were detected. It cannot be ruled out that, at least partly, they may be characteristic of the M. m. bactrianus and M. m. gansuensis subspecies, respectively. Thus, the results of the study showed that the nuclear Brca1 gene is a promising molecular genetic marker for the analysis of variability, differentiation, and hybridization of house mice as well for subspecific identification of M. musculus specimens. Despite more rapid evolution of the Cox1 gene, it is not well suited for discrimination of M. m. musculus, M. m. wagneri, M. m. gansuensis specimens and Transcaucasian representatives of M. m. domesticus due to introgression and long-term maintenance of foreign mitochondrial DNA in populations. However, Cox1 gene analysis (along with the diagnostics of animals by nuclear DNA) may be useful for estimation of population differences in M. m. castaneus and M. m. domesticus subspecies.

International audience; The house mouse (Mus musculus domesticus), as a successful invasive species worldwide, has to forage a variety of resources. Subantarctic mice display among the most notable diet shift from the usual omnivorous–granivorous diet, relying on a larger proportion of terrestrial animal prey. In agreement, a recent study of their mandible morphology evidenced an evolution of their mandible shape to optimize incisor biting and hence seize preys. Here, the incisors themselves are the focus of a morphometric analysis combined with a 3D study of their internal structure, aiming at a comparison between subantarctic populations (Guillou island, Kerguelen archipelago) with a range of western European continental, commensal mice. The predatory foraging behavior of Guillou mice was indeed associated with a sharper bevel of the lower incisor, which appears as an efficient morphology for piercing prey. The incisor of these mice also displays a reduced pulp cavity, suggesting slower eruption counterbalancing a reduced abrasion on such soft food material. The dynamics of the ever‐growing incisor may thus allow adaptive incisor sculpting and participate to the success of mice in foraging diverse resources

Hybrid sterility is a critical step in the evolution of reproductive barriers between diverging taxa during the process of speciation. Recent studies of young subspecies of the house mouse revealed a multigenic nature and frequent polymorphism of hybrid sterility genes as well as the recurrent engagement of the meiosis-specific gene PR domain-containing 9 (Prdm9) and X-linked loci. Prdm9-controlled hybrid sterility is essentially chromosomal in nature, conditioned by the sequence divergence between subspecies. Depending on the Prdm9 interallelic interactions and the X-linked Hstx2 locus, the same homologs either regularly recombine and synapse, or show impaired DNA DSB repair, asynapsis, and early meiotic arrest. Thus, Prdm9-dependent hybrid sterility points to incompatibilities affecting meiotic recombination as a possible mechanism of reproductive isolation between (sub)species.

BackgroundMammalian centromeres are satellite-rich chromatin domains that execute conserved roles in kinetochore assembly and chromosome segregation. Centromere satellites evolve rapidly between species, but little is known about population-level diversity across these loci.ResultsWe developed ak-mer based method to quantify centromere copy number and sequence variation from whole genome sequencing data. We applied this method to diverse inbred and wild house mouse (Mus musculus) genomes to profile diversity across the core centromere (minor) satellite and the pericentromeric (major) satellite repeat. We show that minor satellite copy number varies more than 10-fold among inbred mouse strains, whereas major satellite copy numbers span a 3-fold range. In contrast to widely held assumptions about the homogeneity of mouse centromere repeats, we uncover marked satellite sequence heterogeneity within single genomes, with diversity levels across the minor satellite exceeding those at the major satellite. Analyses in wild-caught mice implicate subspecies and population origin as significant determinants of variation in satellite copy number and satellite heterogeneity. Intriguingly, we also find that wild-caught mice harbor dramatically reduced minor satellite copy number and elevated satellite sequence heterogeneity compared to inbred strains, suggesting that inbreeding may reshape centromere architecture in pronounced ways.ConclusionTaken together, our results highlight the power ofk-mer based approaches for probing variation across repetitive regions, provide an initial portrait of centromere variation acrossMus musculus,and lay the groundwork for future functional studies on the consequences of natural genetic variation at these essential chromatin domains.

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.

The companion paper (Rice 2020) found that the centromeric repeats of the Western European house mouse (Mus musculus domesticus) have unusual structure: i) despite moderate pairwise sequence divergence (average = 5.9%), no monomer sequence was common and many hundreds of monomer sequences were observed, ii) local sequence divergence among neighboring monomers was nearly as high as genome-wide divergence, and iii) matching sequences were rare between side-by-side monomers. Here I integrate information from many published studies to formulate a hypothesis for the evolution of this structure. Non-matching sequences of neighboring centromeric monomers is hypothesized to be selectively favored in the context of molecular drive because it reduces the rate of monomer deletion during repair of double strand breaks (DSBs) via the Single Strand Annealing (SSA) pathway. The foundation for the hypothesis is the observation that centromeres of most populations of M. m. domestics reside close to the telomere, i.e., all their chromosomes are telocentrics. This proximity influences repair of centromeric DSBs because it places at least part of the centromere within the Telomere-Affected Repair Region (TARR; a location with increased concentrations of the shelterin-complex proteins that bind telomeres, especially TRF2). Shelterin proteins increase the level of 5’→3’ end resection at DSBs and thereby: i) decrease the frequency of repair via the c- NHEJ pathway, and ii) increase the frequency of homology-directed repair (HD-repair) –including the SSA repair pathway. It is hypothesized that certain ‘trigger’ events (e.g., sub-telomeric deletions) occur in local populations that increase the influence of TARR on the centromere. This increase elevates the occurrence of SSA repair of centromeric DSBs to a level that causes centromeres to begin to gradually shrink. Chronic shrinkage leads to coevolution between centromere size and karyotype number. Once centromeres shrink to a size below a critical minimum (that causes substantially reduced kinetochore size), fusions between non- homologous telocentrics with undersized centromeres produces metacentrics with an expanded centromere size (and a corresponding ‘quantum-jump’ in kinetochore size). These metacentrics: i) accumulate to fixation because they are favored by centromere drive, and ii) are released from the influence of TARR and thereby gradually recover larger centromere size. Fission of metacentrics with enlarged centromeres can next plausibly regenerate pairs of telocentrics with sufficiently large centromeres (which recruit normal-sized kinetochores) to be favored by centromere drive and accumulate to fixation. This fixation completes a cycle of coevolution within genomes that oscillate between two extremes: i) high karyotype number (2N = 40; all telocentrics) with larger centromeres, and ii) low karyotype number (2N << 40; mainly metacentrics) with initially small centromeres that gradually increase in size.

Parallel changes in genotype and phenotype in response to similar selection pressures in different populations provide compelling evidence of adaptation. House mice (Mus musculus domesticus) have recently colonized North America and are found in a wide range of environments. Here we measure phenotypic and genotypic differentiation among house mice from five populations sampled across 21° of latitude in western North America, and we compare our results to a parallel latitudinal cline in eastern North America. First, we show that mice are genetically differentiated between transects, indicating that they have independently colonized similar environments in eastern and western North America. Next, we find genetically-based differences in body weight and nest building behavior between mice from the ends of the western transect which mirror differences seen in the eastern transect, demonstrating parallel phenotypic change. We then conduct genome-wide scans for selection and a genome-wide association study to identify targets of selection and candidate genes for body weight. We find some genomic signatures that are unique to each transect, indicating population-specific responses to selection. However, there is significant overlap between genes under selection in eastern and western house mouse transects, providing evidence of parallel genetic evolution in response to similar selection pressures across North America., Author summary Dissecting the genetic basis of parallel evolution, the independent evolution of similar phenotypes in similar environments among closely related lineages, allows evolutionary biologists to test whether evolution is predictable at the molecular level. Relatively little is still known about the genetics of parallel evolution in quantitative traits. Here we identify significant phenotypic and genomic parallel evolution in quantitative traits across two latitudinal transects of wild house mice in eastern and western North America. We find parallel evolution in thermally adaptive phenotypes (nest building behavior and body mass) and in genes involved in temperature-related traits such as body mass, metabolism, and temperature-sensing using population genomic scans for selection. We also find considerable divergent phenotypic and genomic evolution between eastern and western transects corresponding to known environmental differences between these transects. In this case, the evolution of quantitative traits across similar latitudinal transects involved a mixture of unique and shared responses to selection at the molecular level.

Analysis of contact zones between parapatric chromosomal races can help our understanding of chromosomal divergence and its influence on the speciation process. Monitoring the position and any movement of contact zones can allow particular insights. This study investigates the present (2012&ndash, 2014) and past (1998&ndash, 2002) distribution of two parapatric house mouse chromosomal races&mdash, PEDC (Estreito da Calheta) and PADC (Achadas da Cruz)&mdash, on Madeira Island, aiming to identify changes in the location and width of their contact. We also extended the 1998&ndash, 2002 sampling area into the range of another chromosomal race&mdash, PLDB (Lugar de Baixo). Clinal analysis indicates no major geographic alterations in the distribution and chromosomal characteristics of the PEDC and PADC races but exhibited a significant shift in position of the Rb (7.15) fusion, resulting in the narrowing of the contact zone over a 10+ year period. We discuss how this long-lasting contact zone highlights the role of landscape on mouse movements, in turn influencing the chromosomal characteristics of populations. The expansion of the sampling area revealed new chromosomal features in the north and a new contact zone in the southern range involving the PEDC and PLDB races. We discuss how different interacting mechanisms (landscape resistance, behaviour, chromosomal incompatibilities, meiotic drive) may help to explain the pattern of chromosomal variation at these contacts between chromosomal races.

Background Amylase gene clusters have been implicated in adaptive copy number changes in response to the amount of starch in the diet of humans and mammals. However, this interpretation has been questioned for humans and for mammals there is a paucity of information from natural populations. Results Using optical mapping and genome read information, we show here that the amylase cluster in natural house mouse populations is indeed copy-number variable for Amy2b paralogous gene copies (called Amy2a1 - Amy2a5), but a direct connection to starch diet is not evident. However, we find that the amylase cluster was subject to introgression of haplotypes between Mus musculus sub-species. A very recent introgression can be traced in the Western European populations and this leads also to the rescue of an Amy2b pseudogene. Some populations and inbred lines derived from the Western house mouse (Mus musculus domesticus) harbor a copy of the pancreatic amylase (Amy2b) with a stop codon in the first exon, making it non-functional. But populations in France harbor a haplotype introgressed from the Eastern house mouse (M. m. musculus) with an intact reading frame. Detailed analysis of phylogenetic patterns along the amylase cluster suggest an additional history of previous introgressions. Conclusions Our results show that the amylase gene cluster is a hotspot of introgression in the mouse genome, making it an evolutionary active region beyond the previously observed copy number changes.

The Eurasian house mouseMus musculusis useful for tracing prehistorical human movement related to the spread of farming. We determined whole mitochondrial DNA (mtDNA) sequences (ca. 16,000 bp) of 98 wild-derived individuals of two subspecies,M.m.musculus(MUS) andM.m.castaneus(CAS). We revealed directional dispersals reaching as far as the Japanese Archipelago from their homelands. Our phylogenetic analysis indicated that the eastward movement of MUS was characterised by five step-wise regional extension events: (1) broad spatial expansion into eastern Europe and the western part of western China, (2) dispersal to the eastern part of western China, (3) dispersal to northern China, (4) dispersal to the Korean Peninsula and (5) colonisation and expansion in the Japanese Archipelago. These events were estimated to have occurred during the last 2000–18,000 years. The dispersal of CAS was characterised by three events: initial divergences (ca. 7000–9000 years ago) of haplogroups in northernmost China and the eastern coast of India, followed by two population expansion events that likely originated from the Yangtze River basin to broad areas of South and Southeast Asia, including Sri Lanka, Bangladesh and Indonesia (ca. 4000–6000 years ago) and to Yunnan, southern China and the Japanese Archipelago (ca. 2000–3500). This study provides a solid framework for the spatiotemporal movement of the human-associated organisms in Holocene Eastern Eurasia using whole mtDNA sequences, reliable evolutionary rates and accurate branching patterns. The information obtained here contributes to the analysis of a variety of animals and plants associated with prehistoric human migration.

For more than 100 years, house mice (Mus musculus) have been used as a key animal model in biomedical research. House mice are genetically diverse, yet their genetic background at the global level has not been fully understood. Previous studies have suggested that they originated in South Asia and diverged into three major subspecies, almost simultaneously, approximately 110,000–500,000 years ago; however, they have spread across the world with the migration of modern humans in prehistoric and historic times (∼10,000 years ago to the present day) and have undergone secondary contact, which has complicated the genetic landscape of wild house mice. In this study, we sequenced the whole-genome sequences of 98 wild house mice collected from Eurasia, particularly East Asia, Southeast Asia, and South Asia. Although wild house mice were found to consist of three major genetic groups corresponding to the three major subspecies, individuals representing admixtures between subspecies were more prevalent in East Asia than has been previously recognized. Furthermore, several samples exhibited an incongruent pattern of genealogies between mitochondrial and autosomal genomes. Using samples that likely retained the original genetic components of subspecies with the least admixture, we estimated the pattern and timing of divergence among the subspecies. The estimated divergence time of the three subspecies was 187,000–226,000 years ago. These results will help us to understand the genetic diversity of wild mice on a global scale, and the findings will be particularly useful in future biomedical and evolutionary studies involving laboratory mice established from such wild mice.

Genomic data for the closest relatives of house mice (Mus musculus species complex) are surprisingly limited. Here, we present the first complete genome for a behaviorally and ecologically unique member of the sister clade to house mice, the mound-building mouse, Mus spicilegus. Using read cloud sequencing and de novo assembly we produced a 2.50 Gbp genome with a scaffold N50 of 2.27 Mbp. We constructed >25 000 gene models, of which the majority had high homology to other Mus species. To evaluate the utility of the M. spicilegus genome for behavioral and ecological genomics, we extracted 196 vomeronasal receptor (VR) sequences from our genome and analyzed phylogenetic relationships between M. spicilegus VRs and orthologs from M. musculus and the Algerian mouse, M. spretus. While most M. spicilegus VRs clustered with orthologs in M. musculus and M. spretus, 10 VRs with evidence of rapid divergence in M. spicilegus are strong candidate modulators of species-specific chemical communication. A high quality assembly and genome for M. spicilegus will help to resolve discordant ancestry patterns in house mouse genomes, and will provide an essential foundation for genetic dissection of phenotypes that distinguish commensal from non-commensal species, and the social and ecological characteristics that make M. spicilegus unique.

Genetic divergence and environment influence on speciation process are the great deal studies over recent decades. One of the best ways for exploring the interaction of geography and genetics is the evaluation of hybrids in a contact zone. To understand if there is one or more hybrid zone between house mouse subspecies in Iran and what are the differences comparing these zones with European well-known hybrid zone, we performed this approach. Samples were live-trapped from Ilam city in west for sensu lato M. m. domesticus subspecies, and Neishabur city in north-east of Iran for sensu lato M. m. musculus subspecies. In five experimental groups, male and female mice of the two subspecies were crossed reciprocally to generate F1 hybrids, and then F1 offspring males and females were crossed also reciprocally between siblings to generate F2 hybrids. In the same manner as seen in European hybrid zone, hybridization between female M. m. musculus and male M. m. domesticus of all five groups showed male sterility in F1 generation, but intact female offspring. These sterile males comparing with a parent or healthy males showed low count and more abnormal sperm percentage in morphological and testis histological section studies. Comparing the results from this study with numerous studies carried out during several years on the European hybrid zone showed an equal condition of contact between two subspecies. Genetical elements have kept their same influence on postzygotic reproductive isolation more than environmental effects far from the Europe, here in Iran.

The behavioral and neuronal responses of the males of two closely related species of mice (Mus musculus wagneri, M. spicilegus) to the urine odors of estrus con- and heterospecific females were studied. In two-choice odor tests males significantly longer investigated odor of conspecific females in comparison with heterospecific ones. To investigate neuronal activation in the main and accessory olfactory bulbs (MOB and AOB), one of the methods of functional tomography – manganese-enhanced MRI ( ME-MRI) – was used. There was a significant increase in Mn2+ accumulation in the dorsal section of the posterior part of the MOB in male M. m. wagneri and M. spicilegus exposed to odor of conspecific females compared with the control group males (odor not exposed). There was a local significant increase in manganese accumulation in the dorsal region of the anterior part of the MOB in the case of the exposure of odor of a heterospecific female. The exposure of heptanone-2 to mice resulted not only in an increase in Mn2+ accumulation in certain zones, but also in a significant decrease in the accumulation of Mn2+ in the rest of the olfactory bulbs. A significant increase in the accumulation of MRI contrast in AOB was observed in males only in the case of female urine-conspecific odor exposure. The results support the previously stated assumption of a significant difference in chemical communication systems in two species of mice. A comparison of these results and results obtained previously demonstrated the absence of any differences in behavioral and neuronal responses to con- and heterospecific odors of the house mouse subspecies allopatric (M. m. wagneri) and sympatric (M. m. musculus) to M. spicilegus. This fact does not allow us to assume the effect of the mechanism of “reinforcement” in the process of evolution in the formation of precopulatory reproductive isolation between the sympatric species M. spicilegus and M. musculus.

The nutria or coypu (Myocastor coypus, Molina, 1782) is one of the world’s worst invasive alien species. Nutria have significant harmful effects on natural ecosystems and agricultural industries on a global scale, including in South Korea. Herein, we report the complete mitochondrial genome of M. coypus. The 16,874 bp sequenced genome exhibited a typical rodential mitochondrial gene arrangement, and consisted of the typical set of 37 genes, one replication origin, and a D-loop. The mitogenome of nutria displayed the highest similarity with that of Cuvier’s spiny rat, Proechimys cuvieri, and was distinct from that of the house mouse, Mus musculus. Multigene phylogenetic analysis also revealed that M. coypus was well clustered with other species in Myocastorini, and the overall tree topology accorded well with recent molecular phylogenetic analysis of South American spiny rats. The results will provide information fundamental for the scientific management of the nutria populations in South Korea.

BackgroundHumans routinely attempt to manage pest rodent populations with anticoagulant rodenticides (ARs). We require information on resistance to ARs within rodent populations to have effective eradication programs that minimise exposure in non-target species. Mutations to the VKORC1 gene have been shown to confer resistance in rodents with high proportions of resistance in mice found in all European populations tested. We screened mutations in Mus musculus within Western Australia, by sampling populations from the capital city (Perth) and a remote island (Browse Island). These are the first Australian mouse populations screened for resistance using this method. Additionally, the mitochondrial D-loop of house mice was sequenced to explore population genetic structure, identify the origin of Western Australian mice, and to elucidate whether resistance was linked to certain haplotypes.ResultsNo resistance-related VKORC1 mutations were detected in either house mouse population. A genetic introgression in the intronic sequence of the VKORC1 gene of Browse Island house mouse was detected which is thought to have originated through hybridisation with the Algerian mouse (Mus spretus). Analysis of the mitochondrial D-loop reported two haplotypes in the house mouse population of Perth, and two haplotypes in the population of Browse Island.ConclusionsBoth house mouse populations exhibited no genetic resistance to ARs, in spite of free use of ARs in Western Australia. Therefore weaker anticoagulant rodenticides can be employed in pest control and eradication attempts, which will result in reduced negative impacts on non-target species. Biosecurity measures must be in place to avoid introduction of resistant house mice, and new house mouse subspecies to Western Australia.

International audience; Toxoplasma gondii is a ubiquitous highly prevalent zoonotic protozoan. Cats are the definitive hosts, while all other warm-blooded animals are intermediate hosts for this parasite. Commensal rodents, being the main prey of cats, are probably the major reservoir for T. gondii in the domestic environment. Rodents can acquire infection after ingestion of oocysts that have sporulated in the environment. However, experimental evidence shows that vertical transmission can be sufficient for the perpetuation of transmission between generations of mice. In natural settings, the relative epidemiological importance of vertical transmission over oral transmission is a matter of debate and raises the question of the possibility of a T. gondii cycle in the absence of cats. In the present study, we took advantage of an extensive survey of commensal rodents in Dakar, Senegal, where the house mouse is the predominant putative reservoir of T. gondii. Mice genotypes and spatial location through GPS referencing of all trapping localizations were investigated in relation to T. gondii infection in eight sites of the city of Dakar and on Goree Island. In each sampling site, the occurrence of over-prevalence zones of T. gondii infection was investigated through Kulldorf's statistic using SaTScan software. Genetic structure and relatedness between mice were investigated within each over-prevalence zone, in order to find clues of transmission between related mice. Within each of the four over-prevalence zones identified across nine sites, infected mice belonged to more than one genetic group. No association between the degree of relatedness and the occurrence of T. gondii infection could be detected. These findings suggest an environmental source of infection for mice associated with localized putative foci of environmental contamination and support an oral route of infection for mice from Dakar rather than a cycle based on vertical transmission. However, further investigations based on a denser sampling in different epidemiological contexts are recommended.

Male genitalia are among the most phenotypically diverse morphological traits, and sexual selection is widely accepted as being responsible for their evolutionary divergence. Studies of house mice suggest that the shape of the baculum (penis bone) affects male reproductive fitness and experimentally imposed postmating sexual selection has been shown to drive divergence in baculum shape across generations. Much less is known of the morphology of female genitalia and its coevolution with male genitalia. In light of this, we used a paternal half-sibling design to explore patterns of additive genetic variation and covariation underlying baculum shape and female vaginal tract size in house mice (Mus musculus domesticus). We applied a landmark-based morphometrics approach to measure baculum size and shape in males and the length of the vaginal tract and width of the cervix in females. Our results reveal significant additive genetic variation in house mouse baculum morphology and cervix width, as well as evidence for genetic covariation between male and female genital measures. Our data thereby provide novel insight into the potential for the coevolutionary divergence of male and female genital traits in a mammal.

Major urinary proteins (MUP) are the major component of the urinary protein fraction in house mice (Mus spp.) and rats (Rattus spp.). The structure, polymorphism and functions of these lipocalins have been well described in the western European house mouse (Mus musculus domesticus), clarifying their role in semiochemical communication. The complexity of these roles in the mouse raises the question of similar functions in other rodents, including the Norway rat, Rattus norvegicus. Norway rats express MUPs in urine but information about specific MUP isoform sequences and functions is limited. In this study, we present a detailed molecular characterization of the MUP proteoforms expressed in the urine of two laboratory strains, Wistar Han and Brown Norway, and wild caught animals, using a combination of manual gene annotation, intact protein mass spectrometry and bottom-up mass spectrometry-based proteomic approaches. Cluster analysis shows the existence of only 10 predicted mup genes. Further, detailed sequencing of the urinary MUP isoforms reveals a less complex pattern of primary sequence polymorphism in the rat than the mouse. However, unlike the mouse, rat MUPs exhibit added complexity in the form of post-translational modifications, including the phosphorylation of Ser4 in some isoforms, and exoproteolytic trimming of specific isoforms. Our results raise the possibility that urinary MUPs may have different roles in rat chemical communication than those they play in the house mouse. Shotgun proteomics data are available via ProteomExchange with identifier PXD013986.

Toxoplasma gondii is a zoonotic protozoan with a worldwide occurrence, but the determinants of the current pattern in the geographical distribution of T. gondii lineages and strains remain poorly understood. To test the influence of human trade on T. gondii populations, we conducted a population genetic study of 72 T. gondii animal isolates from Senegal, a West African country in which the ongoing inland progress of invasive murine hosts (introduced in port cities of Senegal since the 16th century by European sailors) is well described. Isolates were mainly collected on free-range poultry, which are considered as relevant bioindicators of T. gondii strain diversity in the domestic environment. Sampling was conducted in two port cities of Senegal (Dakar and Saint-Louis) and in one inland region (Kedougou). Population genetic analyses using 15 microsatellite markers revealed different patterns between port cities where lineages non-virulent for mice (type II, type III, and Africa 4) were predominant, and Kedougou where the mouse-virulent Africa 1 lineage was the most common. By considering the current spatial pattern in the inland progress of invasive rodents in Senegal, our results suggest that the invasive house mouse Mus musculus domesticus counter-selects the Africa 1 lineage in the invaded areas. The comparison of the microsatellite alleles of type II strains from Senegal to type II strains from other areas in Africa and Western Europe, using discriminant analysis of principal components and Network analysis, point to a mainly Western European origin of the type II lineage in Senegal. Collectively, these findings suggest that human-mediated intercontinental migrations of murine hosts are important vectors of T. gondii strains. Differential susceptibility of endemic and introduced murine hosts to various T. gondii strains probably determines the persistence of these strains in the environment, and therefore their availability for human and animal infection., Author summary Toxoplasma gondii is a zoonotic protozoan with a worldwide distribution and which can infects virtually all warm-blooded species, including human. Clinical expression of human toxoplasmosis, as well as T. gondii strains diversity, exhibit contrasting patterns across geographic regions. The determinants of this geographical structure are poorly understood, but a growing body of evidence supports an important role of human-mediated migrations of T. gondii hosts in the intercontinental dissemination of some parasite lineages. The results of our study conducted in Senegal suggest that the invasive house mouse—which was introduced in the port cities of this country through maritime trade since colonial times—has a dramatic influence on the T. gondii populations of invaded areas. This important T. gondii reservoir seems to be a vector for the intercontinental migrations of T. gondii. In addition, it may have a role in the selection (or the counter-selection) of local T. gondii populations found in invaded areas. This study provides insights into the mechanisms shaping T. gondii populations, thereby determining which strains will be available for human and animal infection.

Spermatogenesis is a tuned cascade of processes producing sperm; impairment of any phase of this process can affect fitness of males. The level of impairment can be pronounced in hybrids between genetically divergent populations. To explore the effect of hybridization on sperm quality we produced F1 hybrids from 29 wild derived strains of two house mouse subspecies, M. m. musculus and M. m. domesticus, which diverged 0.5 MY ago. The measured sperm quality traits did not significantly differ between intrasubspecific crosses. Effects of intersubspecific hybridization were dependent on sperm trait and cross direction. The proportion of sperm head abnormalities was increased in F1 intersubspecific hybrids. The frequency of dissociated sperm heads was increased in the M. m. musculus × M. m. domesticus (♀×♂) F1 but decreased in M. m. domesticus × M. m. musculus (♀×♂) F1 hybrids, with the difference in medians being more than 180%. We deduce that the dissociated sperm heads trait is associated with the X chromosome and modulated by interaction with the Y chromosome; nevertheless, the high proportion of unexplained variance (55.46 %) suggests the presence of polymorphic autosomal interactions. The reported differences in sperm quality between cross types may be highly relevant to male fitness in zones of secondary contact between the two subspecies. The cross direction asymmetry in frequency of dissociated sperm heads should favour the M. m. musculus Y chromosome. This is consistent with the spread of the M. m. musculus Y chromosome in nature across the hybrid zone between these two subspecies.

The genomes of classical inbred mouse strains include genes derived from all three major subspecies of the house mouse, Mus musculus. We recently posited that genetic diversity in the immunoglobulin heavy chain (IGH) gene loci of C57BL/6 and BALB/c mice reflect differences in subspecies origin. To investigate this hypothesis, we conducted high-throughput sequencing of IGH gene rearrangements to document IGH variable (IGHV), joining (IGHJ), and diversity (IGHD) genes in four inbred wild-derived mouse strains (CAST/EiJ, LEWES/EiJ, MSM/MsJ, and PWD/PhJ), and a single disease model strain (NOD/ShiLtJ), collectively representing genetic backgrounds of several major mouse subspecies. A total of 341 germline IGHV sequences were inferred in the wild-derived strains, including 247 not curated in the International Immunogenetics Information System. In contrast, 83/84 inferred NOD IGHV genes had previously been observed in C57BL/6 mice. Variability among the strains examined was observed for only a single IGHJ gene, involving a description of a novel allele. In contrast, unexpected variation was found in the IGHD gene loci, with four previously unreported IGHD gene sequences being documented. Very few IGHV sequences of C57BL/6 and BALB/c mice were shared with strains representing major subspecies, suggesting that their IGH loci may be complex mosaics of genes of disparate origins. This suggests a similar level of diversity is likely present in the IGH loci of other classical inbred strains. This must now be documented if we are to properly understand inter-strain variation in models of antibody-mediated disease.

The segregation of homologous chromosomes at the first meiotic division is dependent on the presence of at least one well-positioned crossover per chromosome. In some mammalian species, however, the genomic distribution of crossovers is consistent with a more stringent baseline requirement of one crossover per chromosome arm. Given that the meiotic requirement for crossing over defines the minimum frequency of recombination necessary for the production of viable gametes, determining the chromosomal scale of this constraint is essential for defining crossover profiles predisposed to aneuploidy and understanding the parameters that shape patterns of recombination rate evolution across species. Here, I use cytogenetic methods for in situ imaging of crossovers in karyotypically diverse house mice (Mus musculus domesticus) and voles (genus Microtus) to test how chromosome number and configuration constrain the distribution of crossovers in a genome. I show that the global distribution of crossovers in house mice is thresholded by a minimum of one crossover per chromosome arm, whereas the crossover landscape in voles is defined by a more relaxed requirement of one crossover per chromosome. I extend these findings in an evolutionary metaanalysis of published recombination and karyotype data for 112 mammalian species and demonstrate that the physical scale of the genomic crossover distribution has undergone multiple independent shifts from one crossover per chromosome arm to one per chromosome during mammalian evolution. Together, these results indicate that the chromosomal scale constraint on crossover rates is itself a trait that evolves among species, a finding that casts light on an important source of crossover rate variation in mammals.

13 pages; International audience; Hybridization can generate phenotypes departing from the parental range through many processes: increased variance due to increased heterozygosity, decreased phenotypic integration and altered covariation structure due to changes in the expression of (co)variation generating developmental processes, and transgression that may arise from epistasis and compensatory genes. Morphometric assessment of shape differentiation, variance and covariance may shed light on these processes, especially for complex characters for which the genetic basis has not yet been assessed. The shape of the first upper molar was thus quantified in a cross between inbred strains of the two European subspecies of the house mouse (Mus musculus domesticus and M. m. musculus). Hybrids appeared as moderately transgressive. Morphological variance was increased in F2s, back to levels observed in wild populations. The pattern of variance–covariance was different between the two parental strains, but restored to a wild-type structure in F2s. Finally, F2s displayed a degree of morphological integration comparable to wild populations but lower than observed in the parental strains. This is interpreted as the result of the reshuffling of the standing genetic variation in hybrids that should have restored the expression of (co)variance generating processes made ineffective in parents due to random allele fixation of some loci. Inter-parental differentiation was more important in regions of the tooth developing early during embryogenesis, whereas transgression was more pronounced in late developing regions. Mutations may more easily generate important geometric differences early during tooth development, occurring as a cascade of signalization from the first cusp to initiate onward. Epistasis and constraints of neighboring parts may be more important later, promoting transgression and impeding differentiation.

The first natural chromosomal variation in the house mouse was described nearly 50 years ago in Val Poschiavo on the Swiss side of the Swiss–Italian border in the Central Eastern Alps. Studies have extended into neighboring Valtellina, and the house mice of the Poschiavo-Valtellina area have been subject to detailed analysis, reviewed here. The maximum extent of this area is 70 km, yet it has 4 metacentric races and the standard 40-chromosome telocentric race distributed in a patchwork fashion. The metacentric races are characterized by highly reduced diploid numbers (2n = 22–26) resulting from Robertsonian fusions, perhaps modified by whole-arm reciprocal translocations. The races hybridize and the whole Poschiavo-Valtellina area can be considered a “hybrid zone.” The studies of this area have provided insights into origin of races within hybrid zones, gene flow within hybrid zones and the possibility of speciation in hybrid zones. This provides a case study of how chromosomal rearrangements may impact the genetic structure of populations and their diversification. Fil: Giménez, Mabel Dionisia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; Argentina. University of York; Reino Unido Fil: Förster, Daniel W.. Leibniz-institute For Zoo And Wildlife Research; Alemania. University of York; Reino Unido Fil: Jones, Eleanor P.. University of York; Reino Unido. Fera Science; Reino Unido Fil: Jóhannesdóttir, Fríđa. University of York; Reino Unido. Cornell University; Estados Unidos Fil: Gabriel, Sofia I.. Universidade de Lisboa; Portugal. University of York; Reino Unido Fil: Panithanarak, Thadsin. Burapha University; Tailandia. University of York; Reino Unido Fil: Scascitelli, Moira. University of York; Reino Unido Fil: Merico, Valeria. Universita Di Pavia; Italia Fil: Garagna, Silvia. Universita Di Pavia; Italia Fil: Searle, Jeremy B.. University of York; Reino Unido. Cornell University; Estados Unidos Fil: Hauffe, Heidi C.. Instituto Agrario San Michele All'adige Fondazione Edmund Mach. Centro Ricerca E Innovazione; Italia. University of York; Reino Unido

Variability in the coat color of the house mouse, Mus musculus, provides an opportunity to study the evolution of phenotypes in this species. Here we associated genetic variations with coat color in seven mice from Madagascar that had identical M. m. gentilulus mitochondrial DNA sequences. The entire coding region of the 948-base pair (bp) coat-color-related gene, Mc1r, was shown to have no nonsynonymous changes. However, analyses of the two exon-1 promoter regions—termed 1A (317 bp) and 1B (499 bp)—from a second gene, Asip, which is also involved in the evolution of coat color, revealed two distinct haplotypes in each region. Associations between Asip promoter regions and dorsal color were ambiguous; however, two ventral color types—light and dark gray—were associated with the haplotypes of 1A, as determined by clustering analysis. Notably, the haplotype of the light gray animals was identical to the Asip Aw allele that is associated with white bellies.

Western house mice (Mus musculus domesticus) and common shrews (Sorex araneus) are important models for study of chromosomal speciation. Both had ancestral karyotypes consisting of telocentric chromosomes, and each is subdivided into numerous chromosomal races many of which have resulted from fixation of new mutations (Robertsonian fusions and whole-arm reciprocal translocations). However, some chromosomal races in both species may alternatively have originated through hybridization, with particular homozygous recombinant products reaching fixation. Here, we demonstrate the process of generation of hybrid chromosomal races for the first time in either species using molecular markers. Analysis of centromeric microsatellite markers show that the Mid Valtellina (IMVA) and Upper Valtellina (IUVA) chromosomal races of the house mouse are recombinant products of hybridization of the Lower Valtellina (ILVA) and Poschiavo (CHPO) chromosomal races, supporting earlier theoretical analysis. IMVA and IUVA occupy a small area of the Italian Alps where ILVA makes contact with CHPO. IUVA and CHPO have previously been shown to be reproductively isolated in one village, emphasizing that hybrid chromosomal races in small mammals, as in plants, have the potential to be part of the speciation process.

The house mouse, Mus musculus, is known for its highly conserved morphology and chromosomal structure, but some chromosomal characters have been recognized as accurate taxonomic markers in this species, e.g. centromeric heterochromatin, which is useful to identify the taxonomic status of house mouse. In this study, comprehensive cytogenetic surveys have been carried out in five to eighteen specimens of house mouse from each locality of Iran using centromeric heterochromatin banding (C-banding). C-banding was performed on the karyotype, and the centromeric heterochromatin region size (CHRs) was calculated using karyotype analysis software. Results indicated that intra- and inter- population variation of C-band positive heterochromatin ranged from very large CHRs to small CHRs. Generally, chromosomes 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 15, 16 and 19 showed high variability in their CHRs whereas chromosomes 1, 2, 3, 13, 17, 18 and X had low variability in CHRs. Chromosome 4 had the largest CHRs in all ...

Although diverse complexes of chromosome races are of rather rare occurrence in mammals, that does not reduce its importance to insignificant phenomenon not worthy of studying as some unique case without direct analogy. Moreover, these complexes present virtually ideal models for estimation of the impact of hybridization on the process of microevolution. The chromosome races are characterized by almost zero level of genetic differentiation and well-defined distinctions, usually induced by chromosome rearrangements only. The presented review shows the valuable contribution of the studies on Sorex araneus and Mus domesticus chromosome Robertsonian systems into our understanding of varied impacts of hybridization on the speciation process. Particularly, it promotes better understanding of such evolutionary phenomena as "reinforcement" of reproductive isolation in secondary contact zones between divergent populations, speciation without geographic separation ("divergence with gene flow"), and "zonal raciation".

Host‐parasite interaction studies across hybrid zones often focus on host genetic variation, treating parasites as homogeneous. ‘Intimately’ associated hosts and parasites might be expected to show similar patterns of genetic structure. In the literature, factors such as no intermediate host and no free‐living stage have been proposed as ‘intimacy’ factors likely constraining parasites to closely follow the evolutionary history of their hosts. To test whether the whipworm, Trichuris muris, is intimately associated with its house mouse host, we studied its population genetics across the European house mouse hybrid zone (HMHZ) which has a strong central barrier to gene flow between mouse taxa. T. muris has a direct life cycle and nonmobile free stage: if these traits constrain the parasite to an intimate association with its host we expect a geographic break in the parasite genetic structure across the HMHZ. We genotyped 205 worms from 56 localities across the HMHZ and additionally T. muris collected from sympatric woodmice (Apodemus spp.) and allopatric murine species, using mt‐COX1, ITS1‐5.8S‐ITS2 rDNA and 10 microsatellites. We show four haplogroups of mt‐COX1 and three clear ITS1‐5.8S‐ITS2 clades in the HMHZ suggesting a complex demographic/phylogeographic history. Microsatellites show strong structure between groups of localities. However, no marker type shows a break across the HMHZ. Whipworms from Apodemus in the HMHZ cluster, and share mitochondrial haplotypes, with those from house mice. We conclude Trichuris should not be regarded as an ‘intimate’ parasite of the house mouse: while its life history might suggest intimacy, passage through alternate hosts is sufficiently common to erase signal of genetic structure associated with any particular host taxon.

One of the major challenges in evolutionary biology is the identification of the genetic basis of postzygotic reproductive isolation. Given its pivotal role in this process, here we explore the drivers that may account for the evolutionary dynamics of the PRDM9 gene between continental and island systems of chromosomal variation in house mice. Using a data set of nearly 400 wild-caught mice of Robertsonian systems, we identify the extent of PRDM9 diversity in natural house mouse populations, determine the phylogeography of PRDM9 at a local and global scale based on a new measure of pairwise genetic divergence, and analyze selective constraints. We find 57 newly described PRDM9 variants, this diversity being especially high on Madeira Island, a result that is contrary to the expectations of reduced variation for island populations. Our analysis suggest that the PRDM9 allelic variability observed in Madeira mice might be influenced by the presence of distinct chromosomal fusions resulting from a complex pattern of introgression or multiple colonization events onto the island. Importantly, we detect a significant reduction in the proportion of PRDM9 heterozygotes in Robertsonian mice, which showed a high degree of similarity in the amino acids responsible for protein–DNA binding. Our results suggest that despite the rapid evolution of PRDM9 and the variability detected in natural populations, functional constraints could facilitate the accumulation of allelic combinations that maintain recombination hotspot symmetry. We anticipate that our study will provide the basis for examining the role of different PRDM9 genetic backgrounds in reproductive isolation in natural populations.

The composition of the mammalian gut microbiota can be influenced by a multitude of environmental variables such as diet and infections. Studies investigating the effect of these variables on gut microbiota composition often sample across multiple separate populations and habitat types. In this study we explore how variation in the gut microbiota of the house mouse (Mus musculus domesticus) on the Isle of May, a small island off the east coast of Scotland, is associated with environmental and biological factors. Our study focuses on the effects of environmental variables, specifically trapping location and surrounding vegetation, as well as the host variables sex, age, body weight and endoparasite infection, on the gut microbiota composition across a fine spatial scale in a freely interbreeding population. We found that differences in gut microbiota composition were significantly associated with the trapping location of the host, even across this small spatial scale. Sex of the host showed a weak association with microbiota composition. Whilst sex and location could be identified as playing an important role in the compositional variation of the gut microbiota, 75% of the variation remains unexplained. Whereas other rodent studies have found associations between gut microbiota composition and age of the host or parasite infections, the present study could not clearly establish these associations. We conclude that fine spatial scales are important when considering gut microbiota composition and investigating differences among individuals. This work was supported by The Natural Environment Research Council (NERC) [grant number NE/L002604/1] as part of the Envision Doctoral Training Programme studentship (URL: https://nerc.ukri.org/) which was awarded to SG. This work was also supported by the Biotechnology and Biological Sciences Research Council [grant number BB/J014508/1], a Doctoral Training Programme studentship (URL: https://bbsrc.ukri.org/) awarded to SY and JF. The funders did not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. peer-reviewed