Hybrid origin of Japanese mice "Mus musculus molossinus": evidence from restriction analysis of mitochondrial DNA

The Japanese mouse, Mus musculus molossinus, has long been considered an independent subspecies of the house mouse. A survey of restriction- site haplotypes of mitochondrial DNA (mtDNA) showed that Japanese mice have two main maternal lineages. The most common haplotype is closely related to the mtDNA of the European subspecies M. m. musculus. The other common haplotype and two minor ones are closely related to each other and to the mtDNA of an Asiatic subspecies, M. m. castaneus. Two other rare variants are probably the result of recent contamination by European M. m. domesticus. The musculus type of mtDNA is found in the southern two-thirds of Japan, whereas the common castaneus type is found in the northern third and the minor variants are found sporadically throughout Japan. The castaneus mtDNA lineage had a few minor variants, whereas the musculus lineage was completely monomorphic. By contrast, the native population of M. m. castaneus and the Chinese and Korean musculus populations were highly polymorphic. These results suggest that M. m. molossinus is a hybrid between ancestral colonies, possibly very small, of M. m. musculus and M. m. castaneus, rather than an independent subspecies.      

Higher differentiation among subspecies of the house mouse (Mus musculus) in genomic regions with low recombination

In the early stages of reproductive isolation, genomic regions of reduced recombination are expected to show greater levels of differentiation, either because gene flow between species is reduced in these regions or because the effects of selection at linked sites within species are enhanced in these regions. Here, we study the patterns of DNA sequence variation at 27 autosomal loci among populations of Mus musculus musculus, M. m. domesticus, and M. m. castaneus, three subspecies of house mice with collinear genomes. We found that some loci exhibit considerable shared variation among subspecies, while others exhibit fixed differences. We used an isolation-with-gene-flow model to estimate divergence times and effective population sizes (N(e) ) and to disentangle ancestral variation from gene flow. Estimates of divergence time indicate that all three subspecies diverged from one another within a very short period of time approximately 350,000 years ago. Overall, N(e) for each subspecies was associated with the degree of genetic differentiation: M. m. musculus had the smallest N(e) and the greatest proportion of monophyletic gene genealogies, while M. m. castaneus had the largest N(e) and the smallest proportion of monophyletic gene genealogies. M. m. domesticus and M. m. musculus were more differentiated from each other than either were from M. m. castaneus, consistent with greater reproductive isolation between M. m. domesticus and M. m. musculus. F(ST) was significantly greater at loci experiencing low recombination rates compared to loci experiencing high recombination rates in comparisons between M. m. castaneus and M. m. musculus or M. m. domesticus. These results provide evidence that genomic regions with less recombination show greater differentiation, even in the absence of chromosomal rearrangements.     

Frequency and distribution of t-haplotypes in the Southeast Asian house mouse (Mus musculus castaneus) in Taiwan

t-haplotypes are a meiotic drive system found on the 17th chromosome of the house mouse (Mus musculus). They can be found in wild populations of all four genetically differentiated subspecies. The drive phenomenon is male-specific, such that heterozygous males (+/t) show non-Mendelian transmission and transmit the t-chromosome to > 90% of their offspring. So far the most comprehensive studies on the frequencies of t-haplotypes in natural populations have been on just one of the subspecies (M. musculus domesticus). We applied molecular methods to accurately screen t-haplotypes in a large number of populations of a second subspecies (M. musculus castaneus) distributed in Taiwan. We found that the overall t-haplotype frequency is low in M. m. castaneus (0.108), and the chromosomes are patchily distributed among its populations, closely resembling the situation found in M. m. domesticus. Further, we found the frequencies of t-haplotypes in our sample did not differ in relation to the sex or age of mice. This resemblance in the frequency and distribution among populations of the two distinct subspecies suggests that similar general mechanisms might be responsible for the low frequencies in both subspecies.     

Genetics and evolution of hybrid male sterility in house mice

Comparative genetic mapping provides insights into the evolution of the reproductive barriers that separate closely related species. This approach has been used to document the accumulation of reproductive incompatibilities over time, but has only been applied to a few taxa. House mice offer a powerful system to reconstruct the evolution of reproductive isolation between multiple subspecies pairs. However, studies of the primary reproductive barrier in house mice-hybrid male sterility-have been restricted to a single subspecies pair: Mus musculus musculus and Mus musculus domesticus. To provide a more complete characterization of reproductive isolation in house mice, we conducted an F(2) intercross between wild-derived inbred strains from Mus musculus castaneus and M. m. domesticus. We identified autosomal and X-linked QTL associated with a range of hybrid male sterility phenotypes, including testis weight, sperm density, and sperm morphology. The pseudoautosomal region (PAR) was strongly associated with hybrid sterility phenotypes when heterozygous. We compared QTL found in this cross with QTL identified in a previous F(2) intercross between M. m. musculus and M. m. domesticus and found three shared autosomal QTL. Most QTL were not shared, demonstrating that the genetic basis of hybrid male sterility largely differs between these closely related subspecies pairs. These results lay the groundwork for identifying genes responsible for the early stages of speciation in house mice.     

A pronounced evolutionary shift of the pseudoautosomal region boundary in house mice

The pseudoautosomal region (PAR) is essential for the accurate pairing and segregation of the X and Y chromosomes during meiosis. Despite its functional significance, the PAR shows substantial evolutionary divergence in structure and sequence between mammalian species. An instructive example of PAR evolution is the house mouse Mus musculus domesticus (represented by the C57BL/6J strain), which has the smallest PAR among those that have been mapped. In C57BL/6J, the PAR boundary is located just ~700 kb from the distal end of the X chromosome, whereas the boundary is found at a more proximal position in Mus spretus, a species that diverged from house mice 2-4 million years ago. In this study we used a combination of genetic and physical mapping to document a pronounced shift in the PAR boundary in a second house mouse subspecies, Mus musculus castaneus (represented by the CAST/EiJ strain), ~430 kb proximal of the M. m. domesticus boundary. We demonstrate molecular evolutionary consequences of this shift, including a marked lineage-specific increase in sequence divergence within Mid1, a gene that resides entirely within the M. m. castaneus PAR but straddles the boundary in other subspecies. Our results extend observations of structural divergence in the PAR to closely related subspecies, pointing to major evolutionary changes in this functionally important genomic region over a short time period.     

Genetic differentiation of subspecies of the house mouse Mus musculus and their taxonomic relationships inferred from RAPD-PCR data

Genetic differentiation of six subspecies of the house mouse Mus musculus (Mus musculus musculus. M. m. domesticus, M. m. castaneus, M. m. gansuensis, M. m. wagneri, and M. m. ssp. (bactrianus?) was examined using RAPD-PCR analysis. In all, 373 loci of total length of about 530 kb were identified. Taxon-specific molecular markers were detected and the levels of genetic differences among the subspecies were estimated. Different degree of subspecific genetic differentiation was shown. The most similar subspecies pairs were M. m. castaneus--M. m. domesticus and M. m. musculus--M. m. gansuensis. In our phylogenetic reconstruction, M. m. wagnery proved to be most different from all the other subspecies. Genetic distances between it and other subspecies were two- to threefold higher than those between the "good"' species of the subgenus Mus (e.g., between M. m. musculus and M. spicilegus, M. musculus and M. abbottii). The estimates of genetic similarity and the taxonomic relationships between six house mouse subspecies inferred from RAPD partially conformed to the results based on cytogenetic and allozyme data. However, they were considerably different from phylogenetic reconstructions based on sequencing of the control mtDNA region, which reflects mutual inconsistency of different systems of inheritance.     

Genetic diversity of the house mouse Mus musculus and geographic distribution of its subspecies-specific RAPD markers on the territory of Russia

Genetic diversity and geographic distribution of taxon-specific RAPD markers was examined in ten local populations of the house mouse Mus musculus (n = 42). The house mice were generally characterized by moderate genetic variation: polymorphism P99 = 60%, P95 = 32.57%; heterozygosity H = 0.12; the observed allele number n(a) = 1.6; the effective allele number n(e) = 1.18; the within-population differentiation Theta = 0.388; and Shannon index I = 0.19. The degree of genetic isolation of individual local populations was greatly variable. The genetic subdivision index G(st) varied from 0.162 to 0.770 at the gene flow of Nm = 2.58-0.149, while the among-population distances D(N) varied from 0.026 to 0.178. of the largest part of the genetic diversity was found among the populations (H(T) = 0.125), while the within-population diversity was twice lower (H(S) = 0.06). The samples examined were well discriminated relative to the sets of RAPD markers. The character distribution pattern provided conditional subdivision of the mice into the "western" and the "eastern" groups with the putative boarder along the Baikal Lake. The first group was characterized by the prevalence of the markers typical of M. m. musculus and M. m. domesticus. The second group was characterized by the prevalence of the markers typical of M. m. musculus, M. m. gansuensis, M. m. castaneus, M. m. domesticus, and m. m. wagneri. The genotype of the nominative subspecies M. m. musculus was background for all populations. In the populations examined some of earlier described subspecies-specific molecular markers were found at different frequencies, pointing to the involvement of several subspecies of M. musculus in the process of hybridization.     

Reduced nucleotide variability at an androgen-binding protein locus (Abpa) in house mice: evidence for positive natural selection.

Previous work has shown that the gene for the alpha subunit of androgen-binding protein, Abpa, may be involved in premating isolation between different subspecies of the house mouse, Mus musculus. We investigated patterns of DNA sequence variation at Abpa within and between species of mice to test several predictions of a model of neutral molecular evolution. Intraspecific variation among 10 Mus musculus domesticus alleles was compared with divergence between M. m. domesticus and M. caroli for Abpa and two X-linked genes, Glra2 and Amg. No variation was observed at Abpa within M. m. domesticus. The ratio of polymorphism to divergence was significantly lower at Abpa than at Glra2 and Amg, despite the fact that all three genes experience similar rates of recombination. Interspecific comparisons among M. m. domesticus, Mus musculus musculus, Mus musculus castaneus, Mus spretus, Mus spicilegus, and Mus caroli revealed that the ratio of nonsynonymous substitutions to synonymous substitutions on a per-site basis (Ka/Ks) was generally greater than one. The combined observations of no variation at Abpa within M. m: domesticus and uniformly high Ka/Ks values between species suggest that positive directional selection has acted recently at this locus.     

Adaptive evolution and effective population size in wild house mice

Estimates of the proportion of amino acid substitutions that have been fixed by selection (α) vary widely among taxa, ranging from zero in humans to over 50% in Drosophila. This wide range may reflect differences in the efficacy of selection due to differences in the effective population size (N(e)). However, most comparisons have been made among distantly related organisms that differ not only in N(e) but also in many other aspects of their biology. Here, we estimate α in three closely related lineages of house mice that have a similar ecology but differ widely in N(e): Mus musculus musculus (N(e) ～ 25,000-120,000), M. m. domesticus (N(e) ～ 58,000-200,000), and M. m. castaneus (N(e) ～ 200,000-733,000). Mice were genotyped using a high-density single nucleotide polymorphism array, and the proportions of replacement and silent mutations within subspecies were compared with those fixed between each subspecies and an outgroup, Mus spretus. There was significant evidence of positive selection in M. m. castaneus, the lineage with the largest N(e), with α estimated to be approximately 40%. In contrast, estimates of α for M. m. domesticus (α = 13%) and for M. m. musculus (α = 12 %) were much smaller. Interestingly, the higher estimate of α for M. m. castaneus appears to reflect not only more adaptive fixations but also more effective purifying selection. These results support the hypothesis that differences in N(e) contribute to differences among species in the efficacy of selection.     

The diverse origins of New Zealand house mice

Molecular markers and morphological characters can help infer the colonization history of organisms. A combination of mitochondrial (mt) D-loop DNA sequences, nuclear DNA data, external measurements and skull characteristics shows that house mice (Mus musculus) in New Zealand and its outlying islands are descended from very diverse sources. The predominant genome is Mus musculus domesticus (from western Europe), but Mus musculus musculus (from central Europe) and Mus musculus castaneus (from southern Asia) are also represented genetically. These subspecies have hybridized to produce combinations of musculus and domesticus nuclear DNA coupled with domesticus mtDNA, and castaneus or musculus mtDNA with domesticus nuclear DNA. The majority of the mice with domesticus mtDNA that we sampled had D-loop sequences identical to two haplotypes common in Britain. This is consistent with long-term British-New Zealand cultural linkages. The origins of the castaneus mtDNA sequences widespread in New Zealand are less easy to identify.     

Acquisition of two endogenous ecotropic murine leukemia viruses in distinct Asian wild mouse populations.

Wild mouse DNAs were analyzed for two types of endogenous ecotropic murine leukemia viruses (MuLVs), Akv and Fv-4r-associated MuLV. Endogenous Akv viruses were found only in northern Chinese mice, Korean mice, and Japanese (Mus musculus molossinus) mice. The Fv-4r gene, which is a truncated endogenous MuLV with ecotropic interference properties, was carried by Southeast Asian (M. m. castaneus) mice, Korean mice, and M. m. molossinus. Sequences related to Fv-4r MuLV env were found only in M. m. castaneus. These findings suggest that endogenous Akv viruses were acquired by northern Chinese mice and that the Fv-4r gene or its related endogenous MuLVs were acquired independently by M. m. castaneus. The Fv-4r gene appears to have been generated hundreds of thousands of years ago, before the amplification of the Fv-4r-related endogenous MuLVs in M. m. castaneus. The coexistence of Akv viruses and the Fv-4r gene in M. m. molossinus may be explained by the hybrid origin of M. m. molossinus in crosses between northern Chinese mice and M. m. castaneus, as described in other articles. The absence of the Fv-4r-related endogenous MuLVs in M. m. molossinus may indicate that the ancestral mice of this subspecies either were an ancient type of M. m. castaneus that had acquired the Fv-4r gene but had not yet acquired the Fv-4r-related endogenous MuLVs or were a rare fraction of a mixed population of M. m. castaneus and northern Chinese mice.     

Genetic differentiation of house mice in the fauna of the former U.S.S.R.: results of cytogenetic studies

A cytogenic study of nearly 200 house mice (Mus musculus sensu stneto) and aboriginal mice (Mus hortulanus, Mus abbotti) of the subgenus Mus was carried out. Mice were sampled from most localities in the former U.S.S.R., from the western borders to the Far East, and it was shown that it is possible to use cytogenetic markers to classify the species and rare subspecies of the subgenus. Such markers included the characteristic morphology of the sex chromosomes and the pattern of distribution of the C-heterochromatin in the karyotype. Thus, the aboriginal mice, together with M. spretus , are characterized by a significant reduction in the size of the Y chromosome. In addition, the variant of the X chromosome (so called 'molossinus' lype) previously only observed in Japanese M. in. molossinus was found in all the Mus musculus sampled from the fauna of the former U.S.S.R. Another type, the so called 'domeslicus' is a plesiomorphic variant of the X chromosome which is normally found in M. domestuus. M. hortulanus, M. abbotti and possibly in M. spretus. The presence of the common variant X chromosome in the house mice of the various subspecies in the fauna of the former U.S.S.R., Mongolia (raddei) and Japan (molossinus) provides the basis for the integration of Asian house mice into the one species, At. musculus sensu stricto. The problems of morphology, ecology and systematics of the mouse fauna of the former U.S.S.R. are also discussed with special attention being paid to the studies of the so called 'wagnen' form.     

Genetic differentiation of subspecies of the house mouse Mus musculus and their taxonomic relationships inferred from RAPD-PCR data

Genetic differentiation of six subspecies of the house mouse Mus musculus (Mus musculus musculus, M. m. domesticus, M. m. castaneus, M. m. gansuensis, M. m. wagneri, and M. m. ssp. (bactrianus?) was examined using RAPD-PCR analysis. In all, 373 loci of total length of about 530 kb were identified. Taxonspecific molecular markers were detected and the levels of genetic differences among the subspecies were estimated. Different degree of subspecific genetic differentiation was shown. The most similar subspecies pairs were M. m. castaneus-M. m. domesticus and M. m. musculus-M. m. gansuensis. In our phylogenetic reconstruction, M. m. wagneri proved to be most different from all the other subspecies. Genetic distances between it and other subspecies were two-to threefold higher than those between the “good”species of the subgenus Mus (e.g., between M. m. musculus and M. spicilegus, M. musculus and M. abbotti). The estimates of genetic similarity and the phylogenetic relationships between six house mouse subspecies inferred from RAPD partially conformed to the results based on cytogenetic and allozyme data. However, they were considerably different from phylogenetic reconstructions based on sequencing of the control mtDNA region, which reflects mutual inconsistency of different systems of inheritance.     

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.     

Phylogeographic origin of Hokkaido house mice (Mus musculus) as indicated by genetic markers with maternal, paternal and biparental inheritance

We examined intraspecies genetic variation in house mice (Mus musculus molossinus) from the northern third of the Japanese Islands, in order to obtain evidence of the history of mouse colonization that might have shaped the current genetic diversity. We extended the previous sampling of mitochondrial cytochrome b sequence and added information from the Y-linked Sry gene and ribosomal RNA gene surveys. We distinguish mitochondrial haplotypes characteristic of the North Asian musculus subspecies group (involving M. m. musculus and M. m. molossinus) as 'MUS', and that of the Southeast Asian castaneus subspecies group as 'CAS' (although the mice resemble MUS morphologically). There was a clear geographic partition of MUS and CAS types into southern and northern Hokkaido, respectively. Conversely, on Tohoku, the MUS and CAS types were interspersed without clear geographic subdivision. In contrast to the mtDNA data, all Hokkaido and Tohoku mice examined were found to possess a unique type for the Y-linked Sry gene, specific to Korea and Japan. Restriction site analysis of nuclear rDNA probe showed a consistent distribution of MUS and CAS types, as major and minor components, respectively, in the Hokkaido and Tohoku mice. These data support the previous notion that the Hokkaido and Tohoku mice experienced genetic hybridization between primary residents of CAS origin and MUS newcomers arriving via a southern route. The invasion of the MUS type could correspond with the evidence for arrival of prehistoric peoples. There are, however, alternative interpretations, including genetic admixture between MUS arriving by a southern route and CAS from a northern route.     

Genetic dissection of a key reproductive barrier between nascent species of house mice

Reproductive isolation between species is often caused by deleterious interactions among loci in hybrids. Finding the genes involved in these incompatibilities provides insight into the mechanisms of speciation. With recently diverged subspecies, house mice provide a powerful system for understanding the genetics of reproductive isolation early in the speciation process. Although previous studies have yielded important clues about the genetics of hybrid male sterility in house mice, they have been restricted to F1 sterility or incompatibilities involving the X chromosome. To provide a more complete characterization of this key reproductive barrier, we conducted an F2 intercross between wild-derived inbred strains from two subspecies of house mice, Mus musculus musculus and Mus musculus domesticus. We identified a suite of autosomal and X-linked QTL that underlie measures of hybrid male sterility, including testis weight, sperm density, and sperm morphology. In many cases, the autosomal loci were unique to a specific sterility trait and exhibited an effect only when homozygous, underscoring the importance of examining reproductive barriers beyond the F1 generation. We also found novel two-locus incompatibilities between the M. m. musculus X chromosome and M. m. domesticus autosomal alleles. Our results reveal a complex genetic architecture for hybrid male sterility and suggest a prominent role for reproductive barriers in advanced generations in maintaining subspecies integrity in house mice.     

Variation in the distribution of silver-staining nucleolar organizer regions on the chromosomes of the wild mouse, Mus musculus.

A silver staining method was used to analyze the distribution of nucleolar organizer regions (Ag-NORs) on chromosomes of 45 wild mice (Mus musculus). The four subspecies represented were M. m. musculus, M. m. molossinus, M. m. castaneus, and M. m. bactrianus. Ag-NORs were observed near the centromeric regions of 11 chromosomes (4, 8, 9, 10, 11, 12, 15, 16, 17, 18, and 19), indicating a preponderance of Ag-NORs on smaller chromosomes. The first five loci have not been observed previously. It is suggested that a correlation may exist between the specific features of mouse Ag-NORs and the events involved in intra- and interchromosomal homogenization of rDNA.     

Genetic and taxonomic diversity of the house mouse Mus musculus from the asian part of the former Soviet Union

Genetic diversity of the house mouse Mus musculus from 12 local populations (n = 65) of the central and eastern parts of the former Soviet Union was examined using RAPD-PCR. About 400 loci were identified, encompassing approximately 500 kb of the mouse genome. Genetic diversity was assessed using NTSYS, POPGENE, TFPGA, and TREECON software programs. In general, the house mouse sample from the regions examined was characterized by moderate genetic variation: polymorphism P = 95.6%, P99 = 60.7%, P95 = 24.2%; heterozygosity H = 0.089; the mean observed number of alleles n(a) = 1.97; effective number of alleles n = 1.13; intrapopulation differentiation deltaS = 0.387; gene diversity h = 0.09. Individual local populations displayed different levels of genetic isolation: the genetic subdivision index G(st) varied from 0.086 to 0.324 at gene flow Nm varying from 5.3 to 1.05, while the interpopulation genetic distance D(N) ranged from 0.059 to 0.186. Most of the genetic diversity of the total sample resided within the local populations: H(S) = 0.6, total gene diversity H(T) = 0.09. The exact test for differentiation, however, did not confirm the affiliation of all the mice examined to one population: chi2 = 1446, d.f. = 724, P = 0.000. Molecular markers specific to four subspecies (musculus, castaneus, gansuensis, and wagneri) were identified. Moreover, in some cases the populations and individual animals exhibited traits of different subspecies, suggesting their introgressive hybridization. It was demonstrated that the house mouse fauna on the territories investigated was characterized by the prevalence of musculus-specific markers, while gansuensis-specific markers ranked second. The castaneus-specific markers were highly frequent in the Far East, but almost absent in Central Asia, where wagneri-specific markers were detected. It was suggested that house mice from Turkmenistan could belong to one of the southern subspecies, which had not deeply penetrated into the Asian fauna of the former Soviet Union. In phenogenetic (UPGMA) and phylogenetic (NJ) reconstructions this form with the high bootstrap support was placed at the tree base, while the isolation of other clusters was not statistically significant. It is thus likely that the house mice from Turkmenistan are closest to the ancestral form of the genus Mus on the territory of the former Soviet Union.     

Mosaic genealogy of the Mus musculus genome revealed by 21 nuclear genes from its three subspecies

Patterns of genetic variation provide insight into the evolutionary history of a species. Mouse (Mus musculus) is a good model for this purpose. Here we present the analysis of genealogies of the 21 nuclear loci and one mitochondrial DNA region in M. musculus based on our nucleotide sequences of nine inbred strains from three M. musculus subspecies (musculus, domesticus, and castaneus) and one M. spicilegus strain as an outgroup. The mitochondrial DNA gene genealogy of those strains confirmed the introgression pattern of one musculus strain. When all the nuclear DNA data were concatenated to produce a phylogenetic tree of nine strains, musculus and domesticus strains formed monophyletic clusters with each other, while the two castaneus strains were paraphyletic. When each DNA region was treated independently, the phylogenetic networks revealed an unnegligibly high level of subspecies admixture and the mosaic nature of their genome. Estimation of ancestral and derived population sizes and migration rates suggests the effects of ancestral polymorphism and gene flow on the pattern of genetic variation of the current subspecies. Gene genealogies of Fut4 and Dfy loci also suggested existence of the gene flow between M. musculus and M. spicilegus or other distant species.     

Salivary androgen-binding protein variation in Mus and other rodents.

We have searched for genetic variation in the expression of salivary androgen-binding protein (ABP) in a wide variety of mice and other rodents. ABP was present in the salivas of mice of all species and subspecies studied. Genetic studies have identified three common variants of the ABP Alpha subunit (Abpaa, Abpab, and Abpac) in Mus musculus populations with distributions that correspond roughly to those of the subspecies studied (domesticus, musculus, and castaneus, respectively). It appears that the ABP a and b polymorphisms conform to the hybrid zone between the domesticus and musculus subspecies characterized by others. Our studies suggest that the presence of Abpab in inbred strains may be due to a M. m. musculus contribution, perhaps via oriental fancy mice bred to European mice in the early lines leading to the common inbred strains. The relatively common occurrence of the ABP a type in other Mus species leads us to conclude that it is the ancestral type in mice. Further, the observation of what amounts to unique alleles in the three different subspecies indicates that microevolution of the protein has occurred. In a broader survey, ABP was also found in the salivas of Murid and Cricetid rodents generally. These findings suggest that ABP has an important functional role in rodent salivas.