Patterns of morphological evolution in the mandible of the house mouse Mus musculus (Rodentia: Muridae)

The worldwide distributed house mouse, Mus musculus, is subdivided into at least three lineages, Mus musculus musculus, Mus musculus domesticus, and Mus musculus castaneus. The subspecies occur parapatrically in a region considered to be the cradle of the species in Southern Asia (‘central region’), as well as in the rest of the world (‘peripheral region’). The morphological evolution of this species in a phylogeographical context is studied using a landmark‐based approach on mandible morphology of different populations of the three lineages. The morphological variation increases from central to peripheral regions at the population and subspecific levels, confirming a centrifugal sub‐speciation within this species. Furthermore, the outgroup comparison with sister species suggests that M. musculus musculus and populations of all subspecies inhabiting the Iranian plateau have retained a more ancestral mandible morphology, suggesting that this region may represent one of the relevant places of the origin of the species. Mus musculus castaneus, both from central and peripheral regions, is morphologically the most variable and divergent subspecies. Finally, the results obtained in the present study suggest that the independent evolution to commensalism in the three lineages is not accompanied by a convergence detectable on jaw morphology. © 2012 The Linnean Society of London, Biological Journal of the Linnean Society, 2012, 105 , 635–647.     

Origin of the House Mice (Superspecies Complex Mus musculus sensu lato) from the Transcaucasia Region: A New Look at Dispersal Routes and Evolution

We analyzed our results and literature evidence on variability of nuclear protein genes in 39 populations of eight commensal and wild species of house mice (superspecies complexesMus musculus and M. spicilegus) from Transcaucasia, Eastern and Western Europe, Near and Middle East, Central, South, and East Asia, and Cuba. These data were for the first time ever combined into a single database by unification of nomenclature of 21 loci examined by different authors in 39 populations. Analysis of geographical allele distribution have shown that populations of domestic Transcaucasian mice are close to Indo-Pakistani populations of form oriental of the species M. castaneus, which preserved a high level of ancestral polymorphism. We concluded that a very heterogeneous, rich gene pool of house mice from Transcaucasia could not develop only by secondary contacts of differentiated M. musculus s. str. and M. domesticus forms, since it is similar to the ancestral gene pool of the superspecies complexes M. musculus and M. spicilegus. In this context, unique characteristics of some Central Asian populations were examined; these populations may have served as a transit station in the dispersal of commensal house mice forms. We suggest that the Transcaucasian populations are genealogically closely related to an early Near East form of M. musculus, which, as M. domesticus and M. castaneus, split from the common ancestor and preserved nondifferentiated pool of ancestral alleles of protein genes. This hypothesis admits the involvement of differentiated species M. musculus s. str. and M. domesticus in the ultimate formation of the gene pool of Transcaucasian house mice. Apparently, these populations resulted from alternation and (or) overlapping of different evolutionary processes. A scenario suggesting that hybrid events having occurred in Transcaucasia at different times, were superposed on the gene pool of the ancient autochtonous population of house mice from this region seems most plausible. Analysis of allozyme variability in the modern Transcaucasian Mus populations could not always distinguish between ancestral polymorphism and hybridization consequences.     

Maternal–foetal genomic conflict and speciation: no evidence for hybrid placental dysplasia in crosses between two house mouse subspecies

Interspecific hybridization between closely related mammalian species, including various species of the genus Mus, is commonly associated with abnormal growth of the placenta and hybrid foetuses, a phenomenon known as hybrid placental dysplasia (HPD). The role of HPD in speciation is anticipated but still poorly understood. Here, we studied placental and foetal growth in F₁ crosses between four inbred mouse strains derived from two house mouse subspecies, Mus musculus musculus and Mus musculus domesticus. These subspecies are in the early stage of speciation and still hybridize in nature. In accordance with the maternal–foetal genomic conflict hypothesis, we found different parental influences on placental and foetal development, with placental weight most affected by the father's body weight and foetal weight by the mother's body weight. After removing the effects of parents’ body weight, we did not find any significant differences in foetal or placental weights between intra‐subspecific and inter‐subspecific F₁ crosses. Nevertheless, we found that the variability in placental weight in inter‐subspecific crosses is linked to the X chromosome, similarly as for HPD in interspecific mouse crosses. Our results suggest that maternal–foetal genomic conflict occurs in the house mouse system, but has not yet diverged sufficiently to cause abnormalities in placental and foetal growth in inter‐subspecific crosses. HPD is thus unlikely to contribute to speciation in the house mouse system. However, we cannot rule out that it might have contributed to other speciation events in the genus Mus, where differences in the levels of polyandry exist between the species.     

Variation in mandible shape and body size of house mice Mus musculus in five separate New Zealand forest habitats

This study investigates variation in house mouse Mus musculus body size and mandible shape across New Zealand, using geometric morphometrics and biomechanical advantage analyses. The Mus phylogroups currently known in New Zealand include Mus musculus domesticus, M. m. musculus and M. m. castaneus. We examined samples of house mice inhabiting five different podocarp and beech forest environments across the North and South Islands (Pureora Forest, Zealandia Wildlife Sanctuary, Craigieburn Forest Park, Eglinton Valley and Hollyford Valley). Significant variation in mandible shape and body size was found between all five forest populations. South Island mice had larger bodies and greater mechanical advantage in the temporalis muscle compared with their North Island counterparts. Zealandia Sanctuary mouse mandibles were broader and shorter than South Island mouse mandibles, and had greater masseter muscle advantage. Centroid size and body weight, but not head-body length, varied significantly with two distinct genetic haplotypes. Finally, annual rainfall was the most significant covariate with mandible shape. Higher rainfall locations were generally associated with soft-food related mandible shapes, while lower rainfall correlated with hard-food mandible shapes. This preliminary investigation provides the framework for further research into mandible shape and body size variation in New Zealand house mice.     

What can the geographic distribution of mtDNA haplotypes tell us about the invasion of New Zealand by house mice <Emphasis Type="Italic">Mus musculus</Emphasis>?

We mapped the distribution and diversity of mitochondrial D-loop haplotypes among 502 New Zealand house mice (Mus musculus). By widespread sampling from 74 sites, we identified 14 new haplotypes. We used Bayesian phylogenetic reconstructions to estimate the genetic relationships between the New Zealand representatives of Mus musculus domesticus (all six known clades) and M. m. castaneus (clade HG2), and mice from other locales. We defined four distinct geographic regions of New Zealand with differing haplotype diversity indices. Our Results suggest (a) two independent pre-1840 invasions by mice of different origin (domesticus clade E and castaneus clade HG2) at opposite ends of the country; (b) multiple later invasions by domesticus clades E and F accompanying the post-1840 development of New Zealand port facilities in the central regions, plus limited local incursions by domesticus clades A, B, C and D1; (c) a separate invasion of Chatham I. by castaneus clade HG2; (d) previously undescribed New Zealand haplotypes, potentially the products of localised indigenous mutation, and (e) hybridisation between different lineages.     

Phylogeography of Chinese house mice (Mus musculus musculus/castaneus): distribution,routes of colonization and geographic regions of hybridization

House mice (Mus musculus) are human commensals and have served as a primary model in biomedical, ecological and evolutionary research. Although there is detailed knowledge of the biogeography of house mice in Europe, little is known of the history of house mice in China, despite the fact that China encompasses an enormous portion of their range. In the present study, 535 house mice caught from 29 localities in China were studied by sequencing the mitochondrial D‐loop and genotyping 10 nuclear microsatellite markers distributed on 10 chromosomes. Phylogenetic analyses revealed two evolutionary lineages corresponding to Mus musculus castaneus and Mus musculus musculus in the south and north, respectively, with the Yangtze River approximately representing the boundary. More detailed analyses combining published sequence data from mice sampled in neighbouring countries revealed the migration routes of the two subspecies into China: M. m. castaneus appeared to have migrated through a southern route (Yunnan and Guangxi), whereas M. m. musculus entered China from Kazakhstan through the north‐west border (Xinjiang). Bayesian analysis of mitochondrial sequences indicated rapid population expansions in both subspecies, approximately 4650–9300 and 7150–14 300 years ago for M. m. castaneus and M. m. musculus, respectively. Interestingly, the migration routes of Chinese house mice coincide with the colonization routes of modern humans into China, and the expansion times of house mice are consistent with the development of agriculture in southern and northern China, respectively. Finally, our study confirmed the existence of a hybrid zone between M. m. castaneus and M. m. musculus in China. Further study of this hybrid zone will provide a useful counterpart to the well‐studied hybrid zone between M. m. musculus and Mus musculus domesticus in central Europe.     

Transgressive segregation in a behavioural trait? Explorative strategies in two house mouse subspecies and their hybrids

Hybrid zones between genetically diverged populations are widespread among animals and plants. Their dynamics usually depend on selection against admixture and dispersal of parental forms in the zone. Although indirect estimates of selection have been the target of many studies, dispersal has been neglected. In this study we carried out open field experiments to test whether males of two house mouse subspecies, Mus musculus musculus and Mus musculus domesticus, differ in their propensity to disperse and in their character of exploration. We tested wild‐caught males and males of two wild‐derived inbred strains. In addition, we examined reciprocal F₁ crosses to test the prediction that these hybrids display intermediate behaviours. We revealed that M. m. musculus males were less hesitant to enter the experimental arena than were M. m. domesticus males, but once inside the arena their movements were more timid. F₁ males differed from both parental strains, with longer latencies to enter the arena, but explored the arena in a similar fashion as the M. m. domesticus males, thus displaying transgressive behavioural phenotypes. These results contribute to our knowledge of behavioural divergence between the mouse subspecies, and add a new facet to the study of speciation. © 2012 The Linnean Society of London, Biological Journal of the Linnean Society, 2012, ●●, ●●–●●.     

Recruitment of lysozyme as a major enzyme in the mouse gut: Duplication,divergence, and regulatory evolution

Summary Two major types of lysozymec (M and P) occur in the mouse genus,Mus, and have been purified from an inbred laboratory strain (C58/J) ofM. domesticus. They differ in physical, catalytic, and antigenic properties as well as by amino acid replacements at 6 of 49 positions in the amino-terminal sequence. Comparisons with four other mammalian lysozymesc of known sequence suggest that M and P are related by a gene duplication that took place before the divergence of the rat and mouse lineages. M lysozyme is present in most tissues; achieves its highest concentration in the kidney, lung, and spleen; and corresponds to the lysozyme partially sequenced before from another strain ofM. domesticus. InM. domesticus and several related species, P lysozyme was detected chiefly in the small intestine, where it is probably produced mainly by Paneth cells. A survey of M and P levels in 22 species of muroid rodents (fromMus and six other genera) of known phylogenetic relationships suggests that a mutation that derepressed the P enzyme arose about 4 million years ago in the ancestor of the housemouse group of species. Additional regulatory shifts affecting M and P levels have taken place along lineages leading to other muroid species. Our survey of 187 individuals of wild house mice and their closest allies reveals a correlation between latitude of origin and level of intestinal lysozyme.     

Detection of recombinant haplotypes in wild mice (Mus musculus) provides new insights into the origin of Japanese mice

Japanese house mice (Mus musculus molossinus) are thought to be a hybrid lineage derived from two prehistoric immigrants, the subspecies M. m. musculus of northern Eurasia and M. m. castaneus of South Asia. Mice of the western European subspecies M. m. domesticus have been detected in Japanese ports and airports only. We examined haplotype structuring of a 200 kb stretch on chromosome 8 for 59 mice from throughout Eurasia, determining short segments (≈ 370–600 bp) of eight nuclear genes (Fanca, Spire2, Tcf25, Mc1r, Tubb3, Def8, Afg3l1 and Dbndd1) which are intermittently arranged in this order. Where possible we identified the subspecies origin for individual gene alleles and then designated haplotypes for concatenated alleles. We recovered 11 haplotypes among 19 Japanese mice examined, identified either as ‘intact’ haplotypes derived from the subspecies musculus (57.9%), domesticus (7.9%), and castaneus (2.6%), or as ‘recombinant’ haplotypes (31.6%). We also detected recombinant haplotypes unique to Sakhalin. The complex nature of the recombinant haplotypes suggests ancient introduction of all three subspecies components into the peripheral part of Eurasia or complicated genomic admixture before the movement from source areas. ‘Intact’domesticus and castaneus haplotypes in other Japanese wild mice imply ongoing stowaway introductions. The method has general utility for assessing the history of genetic admixture and for disclosing ongoing genetic contamination.     

Fine-Scale Phylogenetic Discordance across the House Mouse Genome

Population genetic theory predicts discordance in the true phylogeny of different genomic regions when studying recently diverged species. Despite this expectation, genome-wide discordance in young species groups has rarely been statistically quantified. The house mouse subspecies group provides a model system for examining phylogenetic discordance. House mouse subspecies are recently derived, suggesting that even if there has been a simple tree-like population history, gene trees could disagree with the population history due to incomplete lineage sorting. Subspecies of house mice also hybridize in nature, raising the possibility that recent introgression might lead to additional phylogenetic discordance. Single-locus approaches have revealed support for conflicting topologies, resulting in a subspecies tree often summarized as a polytomy. To analyze phylogenetic histories on a genomic scale, we applied a recently developed method, Bayesian concordance analysis, to dense SNP data from three closely related subspecies of house mice: Mus musculus musculus, M. m. castaneus, and M. m. domesticus. We documented substantial variation in phylogenetic history across the genome. Although each of the three possible topologies was strongly supported by a large number of loci, there was statistical evidence for a primary phylogenetic history in which M. m. musculus and M. m. castaneus are sister subspecies. These results underscore the importance of measuring phylogenetic discordance in other recently diverged groups using methods such as Bayesian concordance analysis, which are designed for this purpose.     

Polymerase chain reaction multiplexing of microsatellites and single nucleotide polymorphism markers for quantitative trait loci mapping of wild house mice

We tested 96 microsatellites and 10 single nucleotide polymorphisms for their allelic distribution in two subspecies of the house mouse, Mus musculus musculus and M. m. domesticus. Sixty‐two microsatellites discriminated strain‐specific differences among nine wild‐derived ‘musculus’ and ‘domesticus’ and three ‘classical’ laboratory strains. For efficient genotyping, we optimized multiplex conditions using five microsatellites per polymerase chain reaction. All 10 single nucleotide polymorphisms were also optimized for simultaneous analysis in one reaction using SNaPshot multiplex. The uniform distribution of markers on autosomes and on the X chromosome makes these panels potentially useful tools for quantitative trait loci mapping of wild house mice.     

Evidence for the presence of two sympatric species of mice (genus Mus L.) in southern France based on biochemical genetics

Populations of mice established outdoors as well as indoors have been investigated at 24 loci using starch gel electrophoresis. Two reproductively isolated groups are recognized, one of which is referable to a house mouse subspecies, Mus musculus brevirostris, and the other to a different species, Mus spretus, contrary to the view of Schwarz and Schwarz that only one species of Mus is present in the Mediterranean Basin. The genetic distance between these two groups is larger than between any pair of investigated subspecies of M. musculus. M. m. brevirostris is biochemically almost indistinguishable from M. m. domesticus. On the other hand, M. spretus exhibits several allelic variants unknown or at most very infrequent in M. musculus, as for instance at the lactate dehydrogenase B-chain locus.This work was supported by research grants from the Centre National de la Recherche Scientifique (E.R.A. No. 261) and the Ecole Pratique des Hautes Etudes.     

The telocentric tandem repeat at the p-arm is not conserved in Mus musculus subspecies

Mouse chromosomes, with the exception of the Y chromosome, are telocentric. The telomere at the p-arm is separated from the centromere by the tL1 sequence and TLC tandem repeats. A previous report showed that the TLC array was also conserved in other strains of the subgenus Mus. These results suggest that the TLC arrays promote the stable evolutionary maintenance of a telocentric karyotype in the subgenus Mus. In this study, we investigated the degree of conservation of TLC arrays among a variety of wild-derived inbred strains, all of which are descendants of wild mice captured in several areas of the world. Genomic PCR analysis indicates that the sequential order of telomere-tL1 is highly conserved in all strains, whereas tL1-TLC is not. Next, Southern blot analysis of DNAs isolated from a panel of mouse subspecies showed both Mus musculus domesticus and Mus musculus castaneus subspecies possess TLC arrays. Unexpectedly, this repeat appears to be lost in almost all Mus musculus musculus and Mus musculus molossinus subspecies, which show a clear geographic divide. These results indicate that either other unknown sequences were replaced by the TLC repeat or almost all M. m. musculus and M. m. molossinus subspecies do not have any sequence between the telomere and minor satellites. Our observation suggests that the TLC array might be evolutionarily unstable and not essential for murine chromosomal conformation. This is the first example of the subspecies-specific large genome alterations in mice.     

Clonal and atypical Toxoplasma strain differences in virulence vary with mouse sub-species

The severe virulence of Toxoplasma gondii in classical laboratory inbred mouse strains contradicts the hypothesis that house mice (Mus musculus) are the most important intermediate hosts for its transmission and evolution because death of the mouse before parasite transmission equals death of the parasite. However, the classical laboratory inbred mouse strains (Mus musculus domesticus), commonly used to test Toxoplasma strain differences in virulence, do not capture the genetic diversity within Mus musculus. Thus, it is possible that Toxoplasma strains that are severely virulent in laboratory inbred mice are avirulent in some other mouse sub-species. Here, we present insight into the responses of individual mouse strains, representing strains of the genetically divergent Mus musculus musculus, Mus musculus castaneus and Mus musculus domesticus, to infection with individual clonal and atypical Toxoplasma strains. We observed that, unlike M. m. domesticus, M. m. musculus and M. m. castaneus are resistant to the clonal Toxoplasma strains. For M. m. musculus, we show that this is due to a locus on chromosome 11 that includes the genes that encode the interferon gamma (IFNG)-inducible immunity-related GTPases (Irgs) that can kill the parasite by localising and subsequently vesiculating the parasitophorous vacuole membrane. However, despite the localization of known effector Irgs to the Toxoplasma parasitophorous vacuole membrane, we observed that some atypical Toxoplasma strains are virulent in all the mouse strains tested. The virulence of these atypical strains in M. m. musculus could not be attributed to individual rhoptry protein 5 (ROP5) alleles, a secreted parasite pseudokinase that antagonises the canonical effector Irgs and is indispensable for parasite virulence in laboratory inbred mice (M. m. domesticus). We conclude that murine resistance to Toxoplasma is modulated by complex interactions between host and parasite genotypes and may be independent of known effector Irgs on murine chromosome 11.     

Origin and radiation of the house mouse: mitochondrial DNA phylogeny

On the basis of patterns of allele frequency variation in nuclear genes (Din et al., in press) it has been proposed that the house mouse M. musculus originated in the northern Indian subcontinent, from where it radiated in several directions to form the well-described peripheral subspecies (M. m. domesticus, M. m. musculus and M. m. castaneus). Here we use a mitochondrial DNA (mtDNA) phylogeny to test this hypothesis and to analyse the historical and demographic events that have accompanied this differentiation. This marker also provides a powerful means to check for genetic continuity between the central and peripheral populations. We studied restriction site polymorphism of samples from India and the Middle East as well as samples from the rest of Eurasia and northern Africa. M. m. domesticus and M. m. musculus are both monophyletic for mtDNA and belong to the subspecies-specific mtDNA lineages that have been described previously. Average nucleotide diversity is low in M. m. musculus (0.2–5%). It is not only higher in M. m. domesticus (0.7–0.9%) but the distribution of pairwise divergence is wider, and the rate of evolution in this branch appears to be higher than in M. m. musculus. The nucleotide diversity found in M. m. castaneus (0.4%) is due to the existence of two rather divergent linages with little intralineage variation. These two lineages are part of a diversified bush of the phylogenetic tree that also comprises several previously undescribed branches and includes all samples from the northern Indian subcontinent and Iran. The degree of diversity found in each of the samples from this region is high (1.2–2.4%) although they come from small geographic areas. This agrees well with the idea that the origin of the radiation was in the northern Indian subcontinent. However, as neither haplotypes on the M. m. domesticus nor on the M. m. musculus branches were found in this region, there appear to be important phylogeographic discontinuities between this central region and these peripherial subspecies. On the basis of the present result and the nuclear data (Din et al., in press), we propose that M. musculus originated in the north of the indian subcontinent. Our calibration of the evolutionary rate of mtDNA in mice suggests that the mouse settlement in this region could be as old as 900 000 years. Possibly from there, a first radiation could have reach the Middle East and the Caspian Sea, where the M. m. domesticus and M. m. musculus lineages, respectively, would have started to differentiate a few hundred thousand years ago, and from where they could have colonised the peripheral part of their ranges only recently.M. m. castaneus appears from its mtDNA to be recent offshoot of the northern Indian population. This multiple and gradual radiation ultimately led to recent peripheral secondary contacts, such as the well-known European hybrid zone.     

Mus and Peromyscus chromosome homology established by FISH with three mouse paint probes

Fluorescence-labeled DNA probes constructed from three whole house mouse (Mus domesticus) chromosomes were hybridized to metaphase spreads from deer mouse (Peromyscus maniculatus) to identify homologies between the species. Mus Chr 7 probe hybridized strongly to the ad-centromeric two-thirds of Peromyscus Chr 1q. Most of Mus 3 probe hybridized principally to two disjunct segments of Peromyscus Chr 3. Mus Chr 9 probe hybridized entirely to the whole Peromyscus Chr 7. Three Peromyscus linkage groups were assigned to chromosomes, based on linkage homology with Mus. The data also are useful in interpretation of chromosomal evolutionary history in myomorphic rodents. Received: 1 December 1998 / Accepted: 17 February 1999     

Origin of the house mice (superspecies complex Mus musculus sensu lato) from the Transcaucasian region: A new look at dispersal routes and evolution

We analyzed our results and literature evidence on variability of nuclear protein genes in 39 populations of eight synanthropic and wild species of house mice (superspecies complexes Mus musculus and M. spicilegus) from Transcaucasia, Eastern and Western Europe, Near and Middle East, Central, South, and East Asia, and Cuba. These data were for the first time ever combined into a single database by unification of nomenclature of 21 loci examined by different authors in 39 populations. Analysis of geographical allele distribution have shown that populations of domestic Transcaucasian mice are close to Indo-Pakistani populations of form oriental of the species M. castaneus, which preserved a high level of ancestral polymorphism. We concluded that a very heterogeneous, rich gene pool of house mice from Transcaucasia could not develop only by secondary contacts of differentiated M. musculus s. str. and M. domesticus forms, since it is similar to the ancestral gene pool of the superspecies complexes M. musculus and M. spicilegus. In this context, unique characteristics of some Central Asian populations were examined; these populations may have served as a "transit station" in the dispersal of synanthropic house mice forms. We suggest that the Transcaucasian populations are genealogically closely related to an early Near East form of M. musculus, which, as M. domesticus and M. castaneus, split from the common ancestor and preserved nondifferentiated pool of ancestral alleles of protein genes. This hypothesis admits the involvement of differentiated species M. musculus s. str. and M. domesticus in the ultimate formation of the gene pool of Transcaucasian house mice. Apparently, these populations resulted from alternation and (or) "overlapping" of different evolutionary processes. A scenario suggesting that hybrid events having occurred in Transcaucasia at different times, were "superposed" on the gene pool of the ancient autochtonous population of house mice from this region seems most plausible. Analysis of allozyme variability in the modern Transcaucasian Mus populations could not always distinguish between ancestral polymorphism and hybridization consequences.     

Deep short-read sequencing of chromosome 17 from the mouse strains A/J and CAST/Ei identifies significant germline variation and candidate genes that regulate liver triglyceride levels

Genome sequences are essential tools for comparative and mutational analyses. Here we present the short read sequence of mouse chromosome 17 from the Mus musculus domesticus derived strain A/J, and the Mus musculus castaneus derived strain CAST/Ei. We describe approaches for the accurate identification of nucleotide and structural variation in the genomes of vertebrate experimental organisms, and show how these techniques can be applied to help prioritize candidate genes within quantitative trait loci.     

Evolution of the structure and composition of house mouse satellite DNA sequences in the subgenus Mus (Rodentia: Muridea): a cytogenomic approach

The composition and orientation of the house mouse satellite DNA sequences (minor, major, TLC) were investigated by a FISH and CO-FISH approach in 11 taxa belonging to three clades of the subgenus Mus. Using a phylogenetic framework, our results highlighted two distribution patterns. The TLC satellite, the most recently discovered satellite, was present in all clades but varied quantitatively among species. This distribution supported its appearance in the ancestor of the subgenus followed by independent evolution in species of each clade. In contrast, the minor and major satellites occurred in only two clades of the subgenus indicating the simultaneous and recent amplification of these sequences. In addition, although qualitative differences in the composition and orientation of the satellite sequences were observed among the taxa, none of the features studied were unique to the house mouse and could account for the extensive chromosomal plasticity evidenced in Mus musculus domesticus.