Town Mouse, Country Mouse: adaptation and adaptability in Mus domesticus (M. musculus domesticus)

The generally accepted idea that the house mouse is a single, world-wide species which owes its success largely to commensalism with man is wrong. There are at least five European and two Asian species lumped together under the name Mus musculus, plus another fourteen Asian species in the same genus. The house mouse of western Europe is the one that has been introduced to the Americas and Australasia, as well as being domesticated in the laboratory and ‘fancy’ strains; it is properly described as Mus domesticus. A complication of this particular species is the existence of chromosomal races involving the fusion of pairs of chromosomes, apparently at random. These races seem to be reproductively isolated from normal (2n = 40) mice. They have been described in southern Europe and northern Britain. Genetical studies of wild-living mice have shown the operation of powerful natural selection, contrary to earlier assumptions that most of the polymorphic variation in the species (especially that revealed by electrophoresis) was neutral. The effects of such selection are reduced (but not eliminated) by the deme structure of established mouse populations; this social structure is much less rigid than some laboratory experiments have suggested, because of opportunism by individual mice in replacing dead or debilitated animals, and filling new niches as these become available. Virtually every mouse population is unique, since a population tends to be founded by a small group of animals drawn from a genetically variable ancestral population. This differentiation has allowed laboratory workers to develop inbred strains with characteristic properties; it has also resulted in over 130 sub-species being described from wild caught animals. A substantial proportion of these latter have probably arisen by instant sub-speciation through the founder effect. This is well illustrated by the mice of the Faroe islands, which are often quoted as standard examples of extremely rapid evolution. The adaptive properties of the house mouse that have made it such an effective pest and such a good laboratory animal have enabled it to colonize habitats as different as Antarctic tundra and tropical atolls. The species is an ideal one for the general biological task of dissecting the traits that contribute to this adaptability; the material is largely available for this task in the diversity of local forms established in different habitats and characterized genetical varieties maintained in the laboratory. More is known about M. domesticus than any other mammal, except possibly man; the time is ripe for fusing laboratory work on reproduction, mortality, and behaviour with the information increasingly coming from field studies of wild-living animals.     

Patterns of infection by Salmonella and Yersinia spp. in commensal house mouse (Mus musculus domesticus) populations

AIMS: This study sought to examine the risk posed by house mice transmitting pathogens to livestock on typical mixed-agriculture farms in the UK. METHODS AND RESULTS: In a 10-month longitudinal study at one farm, 222 faecal samples were taken from mice and 57 swabs from the farm environment; 3.2% and 15.8%, respectively, were positive for Yersinia. Seventy-five intestinal samples were taken from house mice from three other farms and 9.3% were positive for Yersinia. The commonest species was Y. enterocolitica (of a wide range of serotypes); all isolates were non-pathogenic, except one of Y. pseudotuberculosis. Salmonella was not isolated from any sample. CONCLUSION: This study provides additional evidence that house mice are generally not significant vectors of either pathogenic Yersinia strains or Salmonella species. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first longitudinal study of Yersinia in any small mammal population, and shows infection to be a dynamic series of generally non-pathogenic, transient infections.     

The dynamic of the t-haplotype in wild populations of the house mouse Mus musculus domesticus in Israel

The t-haplotype, a variant of the proximal part of the mouse chromosome 17, is composed of at least four inversions and is inherited as a single genetic unit. The haplotype causes embryonic mortality or male sterility when homozygous. Genes within the complex are responsible for distortion of Mendelian transmission ratio in males. Thus, the t-haplotype in heterozygous males is transferred to over 95% of the progeny. We examined the dynamic and behavior of the t-haplotype in wild populations of the house mouse in Israel. The Israeli populations show high frequency (15%–20%) of both partial and complete t-carrying mice, supporting the suggestion that the t-complex evolved in the M. domesticus line in the Israeli region. In one population that had the highest frequency of t-carrying individuals, we compared the level of gene diversity between t-carrying and normal mice in the marker’s loci: H-2 locus of the major histocompatibility complex (MHC) on the t-haplotype of chromosome 17, three microsatellites on other chromosomes, and the mitochondrial D-loop. Genetic variability was high in all tested loci in both t and (+) mice. All t mice carried the same chromosome and showed the same H-2 haplotype. While t-carrying mice showed significant H-2 heterozygotes access, (+) mice expressed significant H-2 heterozygote deficiency. There were no differences in the level of gene diversity between t and (+) mice in the other loci. Heterozygosity level at the MHC may be an additional factor in the selective forces balancing the t-haplotype polymorphism.     

Genetic differentiation and habitat partition of Robertsonian house mouse populations (Mus musculus domesticus) of Tunisia

The karyological analysis of Tunisian populations of house mice revealed the existence of a Robertsonian (Rb) chromosomal race carrying nine pairs of metacentric chromosomes in central Tunisia. Divergence estimates showed that they are genetically differentiated from local all-acrocentric populations and have a reduced level of genic variability. The Rb populations are restricted to urban habitats, whereas all-acrocentric populations occur in rural areas. Contact zones between these two types of habitat yield chromosomally polymorphic populations. Analysis of gene flow indicates that it is reduced and limited to populations bordering the contact areas. The reduced genic variability and patchy distribution exhibited by the Tunisian Rb mice do not agree with results from previous studies of the European Rb populations. Two hypotheses are presented to account for this discrepancy based on local differentiation versus introduction of the Tunisian Rb race.     

Genic differentiation and origin of Robertsonian populations of the house mouse (Mus musculus domesticus Rutty)

This paper examines the relation between chromosomal and nuclear-gene divergence in 28 wild populations of the house mouse semi-species, Mus musculus domesticus, in Western Europe and North Africa. Besides describing the karyotypes of 15 of these populations and comparing them to those of 13 populations for which such information was already known, it reports the results of an electrophoretic survey of proteins encoded by 34 nuclear loci in all 28 populations. Karyotypic variation in this taxon involves only centric (or Robertsonian) fusions which often differ in arm combination and number between chromosomal races. The electrophoretic analysis showed that the amount of genic variation within Robertsonian (Rb) populations was similar to that for all-acrocentric populations, i.e. bearing the standard karyotype. Moreover, divergence between the two types of populations was extremely low. These results imply that centric fusions in mice have not modified either the level or the nature of genic variability. The genetic similarity between Rb and all-acrocentric populations is not attributed to the persistence of gene flow, since multiple fusions cause marked reproductive isolation. Rather, we attribute this extreme similarity to the very recent origin of chromosomal races in Europe. Furthermore, genic diversity measures suggest that geographically separated Rb populations have in situ and independent origins. Thus, Rb translocations are probably not unique events, but originated repeatedly. Two models are presented to explain how the rapid fixation of a series of chromosomal rearrangements can occur in a population without lowering variability in the nuclear genes. The first model assumes that chromosomal mutation rates are between 10(-3) and 10(-4) and that populations underwent a series of transient bottlenecks in which the effective population size did not fall below 35. In the second model, genic variability is restored following severe bottlenecks, through gene flow and recombination.     

New Robertsonian populations of the house mouse (Mus musculus domesticus) from north of the Alps]

New Robertsonian (Rb) populations of the house mouse (Mus musculus domesticus) carrying different combinations of centric fusions are reported in France, Switzerland, and Germany. In Alsace (France), the diploid number varied from 2n = 38 to 34; four fusions were present, with Rb(4.12) homozygous in all populations whereas Rb(5.10), Rb(5.7), or Rb(10.14) were found to be segregating. In Switzerland, only all-acrocentric mice (2n = 40) were present in Bern while Rb(5.7) and Rb(9.16) occurred in Basel. In the Konstanz locality from southern Germany, all the mice were homozygous for nine Rb fusions: Rb(1.18), Rb(2.5), Rb(3.6), Rb(4.12), Rb(7.15), Rb(8.17), Rb(9.14), Rb(10.11), and Rb(13.16). The phylogenetic relationship of these new Rb populations with those already known is discussed.     

Natural hybridization between 2 sympatric species of mice, Mus musculus domesticus L. and Mus spretus Lataste

Using protein loci and DNA markers, we show by a multilocus genetic analysis that certain populations of the two sympatric mouse species Mus musculus domesticus and Mus spretus show clear signs of partial introgression. Given the sterility of F1 males and the known partial genetic incompatibilities between the genomes of the two species, our finding does not invalidate the biological species complex, but allows to think that very limited genetic exchanges remain possible even long after the divergence of taxa. This may have some consequences on the dynamics of certain kinds of invasive or advantageous DNAs like transposable elements or pathogen resistance genes.     

The Mus musculus domesticus Tdy allele acts later than the Mus musculus musculus Tdy allele: a basis for XY sex-reversal in C57BL/6-YPOS mice.

Consomic C57BL/6 males, carrying either the Mus musculus musculus-derived C57BL/6 Y chromosome or the Mus musculus domesticus-derived Poschiavinus Y chromosome, were outcrossed to females of the inbred strains C3H/Bi and CXBH/By and to females of the random bred strain MF1/Ola. In a study at 12.5 days post coitum, gonads of XYC57 and XYPOS fetuses were assessed for the presence of testicular cords. It was found that XYPOS fetuses had a later onset of testicular development than XYC57 fetuses. Limb development, which was monitored as a measure of overall development, was unaffected by the strain of Y present. These data were supported by a longitudinal study in which the increased growth rate of the testes relative to undifferentiated gonads, was also shown to be delayed in XYPOS fetuses. The extent of the delay was estimated to be approximately 14 h. It is concluded that this delay in the onset of testicular differentiation must be caused by differences between the two Y-chromosome types, most probably allelic differences in the testis determinant Tdy.     

Two types of mouse (Mus musculus domesticus) Y chromosomes in Quebec.

A Y chromosomal repetitive sequence identified two types of Y chromosomes in mice (Mus musculus domesticus) caught near Ste. Anne de Bellevue, Quebec. One type is apparently identical to the Y chromosome found in Maryland, Delaware, and California, whereas the other type is similar, but not identical, to the Y chromosome present in M.m. poschiavinus, an Alpine race of M.m. domesticus. These findings suggest that the domesticus Y chromosome is highly polymorphic and thus useful for elucidating the relationships among American and European house mouse populations.     

The mitochondrial genome sequence of Mus terricolor: comparison with Mus musculus domesticus and implications for xenomitochondrial mouse modeling

Knowledge of the mitochondrial DNA (mtDNA) sequence of divergent murine species is critical from both a phylogenetic perspective and in understanding nuclear-mitochondrial interactions, particularly as the latter influences our xenocybrid models of mitochondrial disease. To this end, the sequence of the mitochondrial genome of the murine species Mus terricolor (formerly Mus dunni) is reported and compared with the published sequence for the common laboratory mouse Mus musculus domesticus strain C57BL/6J. These species are of interest because xenomitochondrial cybrid mice were created that harbor M. terricolor mtDNA in a M. m. domesticus nuclear background. Although the total of 1763 nucleotide substitutions represents striking heterogeneity, the majority of these are silent, leading to highly conserved protein sequences with only 159 amino acid differences. Moreover, 58% of these amino acid differences represented conservative substitutions. All of the tRNA genes and rRNA genes have homology of 91% or greater. The control region shows the greatest heterogeneity, as expected, with 85% homology overall. Regions of 100% homology were found for Conserved Sequence Block I, Conserved Sequence Block III and the L-strand origin of replication. Complex I genes showed the greatest degree of difference among protein-coding genes with amino acid homology of 91-97% among the seven mitochondrial genes. Complexes III and IV genes show high homology ranging from 98-100%. From these data, complex I differences appear most critical for the viability of M. m. domesticus: M. terricolor cybrids. Moreover, the sequence information reported here should be useful in identifying critical regions for mitochondrial transfer between species, for furthering the understanding of mitochondrial dynamics and pathology in transmitochondrial organisms, and for the study of Mus genus origins.     

Polymorphic HSRs in chromosome 1 of the two semispecies Mus musculus musculus and M. m. domesticus have a common origin in an ancestral population

HSRs (homogeneously staining regions) are the cytological correlates of DNA amplification. In the house mouse, Mus musculus, many populations are polymorphic for the presence or absence of HSRs on chromosome 1. In the semispecies M. m. domesticus the amplified DNA is present within one HSR, whereas in M. m. musculus chromosomes 1 with two HSRs are found. Hybridization of HSR-specific probes to Southern blots of HSR-carrying genomic DNAs from different localities and semispecies revealed similar complex band patterns. the remaining variation is restricted to sequences with a low degree of amplification. Variation is higher between semispecies than within one semispecies. It is assumed that HSRs are derived from one original amplification event and that unequal recombination is the mechanism underlying the length variation of HSRs present today in both semispecies. Evidence from G-banding and in situ hybridization shows that the two HSRs of M. m. musculus originated from a single HSR by means of a paracentric inversion, where one break-point was located within the single HSR and the second outside the HSR. As a consequence of the paracentric inversion the two HSRs of M. m. musculus are permanently linked together. Since exchange of genes between the two semispecies is restricted to a narrow hybrid zone the amplification that gave rise to the HSR most probably occurred prior to the divergence into the semispecies M. m. domesticus and M. m. musculus about 1 million years ago.by D. Schweizer     

Norwegian house mice (Mus musculus musculus/domesticus): distributions, routes of colonization and patterns of hybridization

We investigated the distributions and routes of colonization of two commensal subspecies of house mouse in Norway: Mus musculus domesticus and M. m. musculus. Five nuclear markers (Abpa, D11 cenB2, Btk, SMCY and Zfy2) and a morphological feature (tail length) were used to differentiate the two subspecies and assess their distributions, and mitochondrial (mt) D‐loop sequences helped to elucidate their colonization history. M. m. domesticus is the more widespread of the two subspecies, occupying the western and southern coast of Norway, while M. m. musculus is found along Norway’s southeastern coast and east from there to Sweden. Two sections of the hybrid zone between the two subspecies were localized in Norway. However, hybrid forms also occur well away from that hybrid zone, the most prevalent of which are mice with a M. m. musculus‐type Y chromosome and an otherwise M. m. domesticus genome. MtDNA D‐loop sequences of the mice revealed a complex phylogeography within M. m. domesticus, reflecting passive human transport to Norway, probably during the Viking period. M. m. musculus may have colonized earlier. If so, that leaves open the possibility that M. m. domesticus replaced M. m. musculus from much of Norway, with the widely distributed hybrids a relict of this process. Overall, the effects of hybridization are evident in house mice throughout Norway.     

Location of a contact zone between Mus musculus domesticus and M. m. domesticus with M. m. castaneus mtDNA in southern New Zealand

The house mouse, Mus musculus, was first introduced into New Zealand in significant numbers in the early to mid nineteenth century, with genomic components from different sources of the three subspecies M. m. domesticus, M. m. musculus and M. m. castaneus. M. m. domesticus is now widely distributed in New Zealand, with genomic and morphological evidence of M. m. musculus in a few scattered locations. M. m. domesticus/M. m. castaneus hybrids are dominant in the southern third of the South Island. We anticipated that there should be a definable southern contact zone between pure M. m. domesticus and M. m. domesticus/M. m. castaneus hybrids. We tested this hypothesis by screening 170 DNA samples from mice collected in the southern South Island, using a PCR technique which rapidly distinguishes the mitochondrial genomes of the three subspecies.All mice sampled from in or north of Lincoln (43.63° S) had only M. m. domesticus mtDNA, whereas all those from or further south than Hook (44.68° S) had M. m. castaneus mtDNA. Between the two sites, mice carrying mtDNA of both subspecies were found, sometimes in the same building. On present data, this contact zone extends approximately 50 km north to south and some 30 km inland. Classical tests with three nuclear DNA markers confirmed earlier work showing that the nuclear genomes of all mice appeared to be predominantly domesticus-like.We conclude that if purebred M. m. castaneus mice did originally reach New Zealand, extensive backcrossing with M. m. domesticus has made the castaneus nuclear genome virtually undetectable with the tests that we employ.     

Sex reversal caused by Mus musculus domesticus Y chromosomes linked to variant expression of the testis-determining gene Sry

When the Y chromosomes from certain populations of Mus musculus domesticus are introduced into the mouse strain C57BL/6 (B6), testis determination can fail, resulting in gonads developing either as ovotestes (with both ovarian and testicular components) or as ovaries. Not all Y(DOM) chromosomes cause sex reversal. Y(DOM) chromosomes are divided into three classes based upon their ability to induce testes in B6. The molecular basis underlying the three Y(DOM) classes is an enigma. The simplest explanation is that they harbor different alleles of the testis-determining gene, Sry. Sequencing of Sry(DOM) genes has indeed identified polymorphisms. However, none were unequivocally linked to the sex-reversal trait. It was concluded that all SRY(DOM) proteins are functionally equivalent. Using a semiquantitative RT-PCR assay, we now show that representatives of the three Y(DOM) classes have variant Sry expression patterns, that severity of sex reversal correlates with Sry mRNA titers, and that genetic correction of the sex reversal results in the upregulation of Sry expression. We propose that the variant Sry expression patterns result from polymorphisms at the site of a putative Sry enhancer.     

Construction of a small Mus musculus repetitive DNA library: identification of a new satellite sequence in Mus musculus.

We report the construction of a small library of recombinant plasmids containing Mus musculus repetitive DNA inserts. The repetitive cloned fraction was derived from denatured genomic DNA by reassociation to a Cot value at which repetitive, but not unique, sequences have reannealed followed by exhaustive S1 nuclease treatment to degrade single stranded DNA. Initial characterizations of this library by colony filter hybridizations have led to the identification of a previously undetected M. musculus minor satellite as well as to clones containing M. musculus major satellite sequences. This new satellite is repeated 10-20 times less than the major satellite in the M. musculus genome. It has a repeat length of 130 nucleotides compared with the M. musculus major satellite with a repeat length of 234 nucleotides. Sequence analysis of the minor satellite has shown that it has a 29 base pair region with extensive homology to one of the major satellite repeating subunits. We also show by in situ hybridization that this minor satellite sequence is located at the centromeres and possibly the arms of at least half the M musculus chromosomes. Sequences related to the minor satellite have been found in the DNA of a related Mus species, Mus spretus, and may represent the major satellite of that species.