Linkage-dependent gene flow in a house mouse chromosomal hybrid zone

In the alpine valley of Valtellina there are two Robertsonian chromosomal races of house mouse, the Poschiavo (POS: 2n = 24-26) characterized by metacentric 8.12 and acrocentrics 2 and 10 and the Upper Valtellina (UV: 2n = 22-24) characterized by metacentrics 2.8 and 10.12. The races inhabit separate villages in the valley except in Sommacologna and Sondalo, where they both occur together with hybrids. A total of 179 mice from 16 villages were typed at 13 microsatellite loci. Seven of these loci were localized close to the centromeres of chromosomes 10 and 12, with the prediction that these regions on the race-specific chromosomes would be the most likely to experience a barrier to gene flow. The remaining six loci were localized at the telomeres of chromosomes 10 and 12 and at the centromeres of chromosomes that do not differ between the races. Substantial differences in allelic frequencies were found between the villages with POS and UV races at five of the loci at the centromeres of chromosomes 10 and 12 but at none of the other loci. These differences were not found to distinguish the two races in Sommacologna and Sondalo. Therefore, the centromeric regions of race-specific chromosomes do appear to experience a barrier to gene flow, although this can break down under intense interbreeding between the races. These results are considered in the context of Harrison's (1990) concept of the semipermeability of hybrid zones to gene exchange and in relation to parapatric speciation.     

Raciation and speciation in house mice from the Alps: the role of chromosomes

There are at least 24 different karyotypic races of house mouse in the central Alps, each characterized by a different complement of ancestral acrocentric and derived metacentric chromosomes; altogether 55 different metacentric chromosomes have been described from the region. We argue that this chromosome variation largely arose in situ. If these races were to make contact, in most cases they would produce F1 hybrids with substantial infertility (sometimes complete sterility), due to nondisjunction and germ cell death associated with the formation of long-chain and/or ring configurations at meiosis. We present fertility estimates to confirm this for two particular hybrid types, one of which demonstrates male-limited sterility (in accordance with Haldane's Rule). As well as a model for speciation in allopatry, the Alpine mouse populations are of interest with regards speciation in parapatry: we discuss a possible reinforcement event. Raciation of house mice appears to have happened on numerous occasions within the central Alps. To investigate one possible source of new karyotypic races, we use a two-dimensional stepping stone model to examine the generation of recombinant races within chromosomal hybrid zones. Using field-derived ecological data and laboratory-derived fertility estimates, we show that hybrid karyotypic races can be generated at a reasonable frequency in simulations. Our model complements others developed for flowering plants that also emphasize the potential of chromosomal hybrid zones in generating new stable karyotypic forms.     

Chromosomal variation in the house mouse

Although the standard karyotype of the western house mouse, Mus musculus domesticus , consists entirely of acrocentric chromosomes, there are 97 distinct 'populations' that are characterized by various combinations of metacentric chromosomes that have arisen by Robertsonian (Rb) fusions and whole-arm reciprocal translocations (WARTs). In this review we discuss the processes behind the origin and fixation of these rearrangements and then present a unified list of all known metacentric populations and evaluate their phylogenetic relationships. Eleven independent phylogeographical 'systems', each consisting of 2–25 metacentric populations, were identified in Scotland, Denmark, Northern Europe–Northern Switzerland, Southern Switzerland, Northern Italy, Croatia, Spain, Central–Southern Italy, Peloponnesus, Mainland Greece and Madeira. There are six isolated metacentric populations that do not belong to any of these systems. To generate phylogenies of the metacentric populations within each system, we determined those outcomes with the fewest steps regarding accumulation of metacentrics by Rb fusions, WARTs and zonal raciation and taking into account geographical proximity. These phylogenies should be viewed as working hypotheses that will be refined with further chromosomal and molecular data and improvements in methods of phylogenetic reconstruction. The list of metacentric populations and our phylogenies are also published electronically and can be accessed at http://www.studenec.ivb.cz/Projects/RobertsonianMice/ .  © 2005 The Linnean Society of London, Biological Journal of the Linnean Society , 2005, 84 , 535–563.     

Behavioural discrimination among chromosomal races of the house mouse (Mus musculus domesticus)

This work is concerned with the extent of behavioural discrimination between three chromosomal races of the house mouse (the standard 40-chromosome race and a 32- and 36-chromosome races) found in the vicinity of a hybrid zone in northern Scotland. Mice were investigated for several elements of their social behaviour. Within-population dyadic encounters did not show consistent behavioural differences attributable to karyotype among five populations (two standard race, two 36-chromosome race, one 32-chromosome race). Between-population dyadic encounters revealed significant differences between three populations. The standard population examined appeared to be the most “open” to foreigners, the 32-chromosome population the most “closed” while the 36-chromosome mice displayed an intermediate response. Differences in behaviour displayed during between-population as compared to within-population dyadic encounters revealed the occurrence of behavioural discrimination between populations. The implication of these results on the dynamics of the hybrid zone are discussed.     

Effect of Robertsonian translocations on sperm head form in the house mouse

Sperm morphology reflects a long process of adaptation to external conditions and the barriers encountered before ova fertilization can take place; however, not all morphological variation found in gametes can be explained by the effects of these selective forces, as the genetic component may also contribute to the establishment of different gametic features. In north‐eastern Spain, there is a wide Robertsonian system of Mus musculus domesticus, where individuals with 2n ranging from 27 to 40 chromosomes have been described. To elucidate the effect of the karyotype on sperm head form, a comparative analysis between different chromosomal groups of mice from this zone was carried out. Sperm heads from eight St (2n = 40) and 24 Rb (2n = 30–39) males were processed for scanning electron microscopy and analysed using geometric morphometric techniques. Canonical variate analyses showed substantial shape differences between St and Rb mice in the ventral spur region and between Rb groups in the post‐acrosomal region. Significant differences in sperm head size were also detected between chromosomal groups. Structural disorders related to spermatogenesis, genetic alterations, and epistatic interactions among loci are probably involved in the relationship between the phenotypic variation of the sperm head and Rb translocations. © 2013 The Linnean Society of London, Biological Journal of the Linnean Society, 2013, 110 , 878–889.     

Variation in fluctuating asymmetry levels across a Robertsonian polymorphic zone of the house mouse

Fluctuating asymmetry (FA) levels were assessed within the Barcelona Robertsonian polymorphic zone of Mus musculus domesticus as a measure of developmental instability (DI). This zone is characterized by populations with a reduced diploid number (2n = 27–39) surrounded by others with standard karyotype (2n = 40). Mice were distributed into four classes according to mean diploid number at each collecting site, and differences in their FA levels were studied. Three different FA indices were calculated on interlandmark distances from two major morphogenetic units of the mandible: the teeth and muscular areas. Three kinds of analysis were performed: trait‐by‐trait, considering the two regions separately and pooling all traits. In univariate analyses few differences were detected between classes. Nevertheless, when characters were pooled, differences in FA values were found between one Robertsonian group and standard mice, and between several Robertsonian classes. Teeth area traits showed higher FA levels in Rb I mice, i.e. those geographically close to the standard populations. However, FA levels decreased in more introgressed Robertsonian groups and showed significant differences with Rb I. Muscular area traits showed lower DI levels in the Robertsonian mice, especially those with an intermediate mean diploid number (Rb II). When all traits were pooled, FA levels increased in Rb I, whilst the other Robertsonian groups showed similar, or even lower, FA values to those of the standard mice. The higher FA levels found in Rb I suggest an increase in the disruption of genetic coadaptation. Furthermore, in Rb I the presence of metacentrics is more recent than in more introgressed populations; we therefore suggest that Rb I have had less time to restore genetic coadaptation. In addition, the teeth region of the mandible seems to be more sensitive to genomic stress than the muscular region. In the light of these results we suggest that hybrids should be separated into groups and that mandible morphogenetic units be differentiated when using FA in hybrid zones to analyse DI.     

Structure and biology of house mouse populations that plague irregularly: an evolutionary perspective

In Australia, populations of mice occasionally irrupt into plagues, mainly in the southern and eastern grain-growing regions. Mus domesticus was the only member of the subgenus Mus identified from a genetic survey of animals collected from four states. Little is known of the origin of these mice but they probably came from Europe where plagues do not occur. We examined whether mice have evolved the ability to plague since their colonization by comparing some population parameters of Australian, European and North American mice. Their helminth fauna were contrasted to gauge the importance of founder effects on the evolution of mice in Australia.
Australian mice share 52% (12 of 23) of the helminths found in mice in Europe and North America. Those not shared mainly had indirect life cycles. The absence of species could be explained by a strong founder effect or the lack of suitable intermediate hosts near Australian ports. There was no evidence that population structure or diet had evolved differently. Population abundance was different in field populations especially during the build-up and irruption of plagues. These differences were related to better breeding by mice in Australia in field environments; average number of embryos per litter was substantially higher and breeding seasons longer. Genetic change is not the only explanation for this increased productivity–a combination of lack of interspecific competition from other granivores and more favourable climatic conditions may be responsible.
All things considered, there was no compelling evidence that Australian mice have evolved the ability to plague. Their ability to respond to good conditions by increasing litter size beyond that recorded elsewhere supports the notion that control of mouse productivity is an appropriate management option for plague prevention.     

Genetic structure of insular Mediterranean populations of the house mouse

The genetic structure of six western Mediterranean island populations of Mus musculus domesticus were investigated by means of an electrophoretic analysis at 34 loci and compared to that of five neighbouring mainland populations. No reduction in variability (H = 0.09 for both island and mainland samples) was observed in the island populations except for a very small island (6 ha), in which one-third of the variability was lost. Patterns of colonization inferred from a Wagner cluster analysis and the distribution of rare variants suggest that, although these island populations are clearly related to European mainland mice, their genetic structure is the result of multiple founding events from sources dispersed throughout the Mediterranean Basin. Furthermore, the presence of the same rare alleles in Sardinia, Corsica and Piana, suggest that the three islands share a common history of colonization.
Estimates of genetic distance and gene flow indicate that the level of genie differentiation is greater between island and mainland populations that between the latter due to geographic isolation. Multiple founder events and post-colonization evolution are the factors that best explain the observed levels of genie variability and differentiation in these Mediterranean islands.     

The structure of a chromosomal hybrid zone of house mice (Mus domesticus) in central Italy: cytogenetic analysis

Parapatric hybridization between the chromosomal race “CD” (2n = 22) and standard karyotype populations (2n = 40) of Mus domesticus occurs extensively in central Italy. The present paper reports the results of a ctogenetic surve on a transect crossin the hybrid zone north of Rome. No clinal variation in eitier diloid nuders and chromosome frequencies was found to occur in this area, and drift seems to be responsible for the observed atchy pattern of variation. The previous assumption of a strong fertility reduction in structuray heterozyous hybrids contrasts sharply with the width (32 km) of the zone and the average structural aeterozygosity of the hybrid poulations. It is suggested that fitness of structural heterozygotes in nature is not strongly aPfected as has been inferred from laboratory experiments. The results of this study are discussed in context together with the role of hybrid zones in chromosomal speciation in Mus domesticus.     

Inferences of selection and migration in the Danish house mouse hybrid zone

We analysed the patterns of allele frequency change for ten diagnostic autosomal allozyme loci in the hybrid zone between the house mouse subspecies Mus musculus domesticus and M. m. musculus in central Jutland. After determining the general orientation of the clines of allele frequencies, we analysed the cline shapes along the direction of maximum gradient. Eight of the ten clines are best described by steep central steps with coincident positions and an average width of 8.9 km (support limits 7.6–12.4) flanked by tails of introgression, indicating the existence of a barrier to gene flow and only weak selection on the loci studied. We derived estimates of migration from linkage disequilibrium in the centre of the zone, and by applying isolation by distance methods to microsatellite data from some of these populations. These give concordant estimates of σ =  0.5–0.8 km generation     . The barrier to gene flow is of the order of 20 km (support limits 14–28), and could be explained by selection of a few per cent at 43–120 underdominant loci that reduces the mean fitness in the central populations to 0.45. Some of the clines appear symmetrical, whereas others are strongly asymmetrical, and two loci appear to have escaped the central barrier to gene flow, reflecting the differential action of selection on different parts of the genome. Asymmetry is always in the direction of more introgression into musculus , indicating either a general progression of domesticus into the musculus territory, possibly mediated by differential behaviour, or past movement of the hybrid zone in the opposite direction, impeded by potential geographical barriers to migration in domesticus territory.  © 2005 The Linnean Society of London, Biological Journal of the Linnean Society , 2005, 84 , 593–616.     

Fast evolutionary response of house mice to anthropogenic disturbance on a Sub‐Antarctic island

Invasions and anthropogenic disturbances challenge species with rapid environmental changes. Understanding how organisms respond to these changes is of major concern for the future of biodiversity. The house mouse on a Sub‐Antarctic island (Guillou Island, Kerguelen Archipelago) had to face such challenges twice: first when invading the island two centuries ago; and nowadays when coping with an in‐depth remodeling of its habitat due to a cohort of anthropogenic changes. Morphometric and biomechanical results show that the initial invasion triggered the evolution of a jaw shape adapted to the local food resources. Contemporary changes are also associated to changes in jaw morphology, but are not directly functionally relevant. Here, a complex response integrating feeding behaviour, investment in feeding structure, and degree of mineralization, may provide the mice with a better tool to benefit of wider resources utilization and/or better cope with intra‐specific competition in a changing habitat. These Sub‐Antarctic mice exemplify that success of invasive species rely on the capacity of facing rapidly varying environments through integrated, multi‐faceted responses involving behaviour to morphology through life‐history traits. © 2015 The Linnean Society of London, Biological Journal of the Linnean Society, 2015, 114 , 513–526.     

The genomic basis of high-elevation adaptation in wild house mice (Mus musculus domesticus) from South America

Understanding the genetic basis of environmental adaptation in natural populations is a central goal in evolutionary biology. The conditions at high elevation, particularly the low oxygen available in the ambient air, impose a significant and chronic environmental challenge to metabolically active animals with lowland ancestry. To understand the process of adaptation to these novel conditions and to assess the repeatability of evolution over short timescales, we examined the signature of selection from complete exome sequences of house mice (Mus musculus domesticus) sampled across two elevational transects in the Andes of South America. Using phylogenetic analysis, we show that house mice colonized high elevations independently in Ecuador and Bolivia. Overall, we found distinct responses to selection in each transect and largely nonoverlapping sets of candidate genes, consistent with the complex nature of traits that underlie adaptation to low oxygen availability (hypoxia) in other species. Nonetheless, we also identified a small subset of the genome that appears to be under parallel selection at the gene and SNP levels. In particular, three genes (Col22a1, Fgf14, and srGAP1) bore strong signatures of selection in both transects. Finally, we observed several patterns that were common to both transects, including an excess of derived alleles at high elevation, and a number of hypoxia-associated genes exhibiting a threshold effect, with a large allele frequency change only at the highest elevations. This threshold effect suggests that selection pressures may increase disproportionately at high elevations in mammals, consistent with observations of some high-elevation diseases in humans.     

The house mouse progression in Eurasia: a palaeontological and archaeozoological approach

A palaeontological and archaeozoological survey has allowed us to establish the different steps in the colonization of western Eurasia and northern Africa by the house mouse Mus musculus . After successive immigration waves of the genus Mus into this zone from the late Pliocene to the upper Pleistocene, the house mouse appeared and remained confined to the easternmost Mediterranean Basin at the uppermost Pleistocene. The first progression of this species into the Mediterranean Basin occurred in the Middle East from the Epipaleolithic to the Neolithic. Subsequently, this species was found in the western Mediterranean Basin during the Bronze Age and in north-west Europe during the Iron Age. In comparison to this latter zone, north central Europe was colonized relatively early, from the Neolithic to the Bronze Age which may, in fact, not only correspond to a much earlier invasion of Europe by M. musculus musculus but also suggest that the distribution of this subspecies extended much further west than it does nowadays, at a time when M. musculus domesticus was restricted to the Mediterranean zone. This archaeological survey is in agreement with genetic data which provide indications as to the speed, steps and pathways of progression of house mouse populations in western Eurasia.     

Morphology, growth and reproduction in the Australian house mouse: differential effects of moderate temperatures

The house mouse ( Mus musculus domesticus ) was introduced into Australia two centuries ago and is now succeeding in a wide range of habitats and climatic regions. To explore how mice exploit such extreme environments, we compared growth rate, morphology and reproductive success of animals reared under differing thermal regimes (13 °C 'cool', 22 °C 'moderate' and 30 °C 'warm') in laboratory mice derived from wild stock. 'Warm' group young were smaller and grew more slowly than those from other groups. At 6 weeks of age, body mass was less in 'warm' than in 'cool' treatment individuals; and liver mass/body mass also was less in 'warm' than in 'cool' treatment individuals. Paired kidney mass/body mass and paired adrenal mass/body mass were less in 'warm' than in 'cool' and 'moderate' treatment mice. Low heritability values indicate that these effects were from the temperature treatments rather than genetic influences. Irrespective of temperature treatment, females were more likely to produce a litter from post-partum matings if they were experienced, rather than young or reproductively naïve, and also bore more young from post-partum matings. These observations contribute to understanding of the sudden plague activities of mice in some parts of Australia and also their sparse distribution in the interior of the continent.  © 2008 The Linnean Society of London, Biological Journal of the Linnean Society , 2008, 94 , 21–30.     

Genetic structure of house mouse (Mus musculus Linnaeus 1758) populations in the Atlantic archipelago of the Azores: colonization and dispersal

We analyzed the genetic structure and relationships of house mouse (Mus musculus) populations in the remote Atlantic archipelago of the Azores using nuclear sequences and microsatellites. We typed Btk and Zfy2 to confirm that the subspecies Mus musculus domesticus was the predominant genome in the archipelago. Nineteen microsatellite loci (one per autosome) were typed in a total of 380 individuals from all nine Azorean islands, the neighbouring Madeiran archipelago (Madeira and Porto Santo islands), and mainland Portugal. Levels of heterozygosity were high on the islands, arguing against population bottlenecking. The Azorean house mouse populations were differentiated from the Portuguese and Madeiran populations and no evidence of recent migration between the three was obtained. Within the Azores, the Eastern, Western, and Central island groups tended to act as separate genetic units for house mice, with some exceptions. In particular, there was evidence of recent migration events among islands of the Central island group, whose populations were relatively undifferentiated. Santa Maria had genetically distinctive mice, which may relate to its colonization history. © 2013 The Linnean Society of London     

Influence of physical environmental characteristics and anthropogenic factors on the position and structure of a contact zone between two chromosomal races of the house mouse on the island of Madeira (North Atlantic, Portugal)

Aim This study aimed to investigate if and how environmental characteristics (physical factors of the natural environment and the human impact on the landscape) influence the position and structure of a contact zone between two chromosomal races of the house mouse (Mus musculus domesticus Rutty 1712) from the island of Madeira. Location The western part of Madeira, a volcanic island in the North Atlantic. Methods Mice were sampled along a south/north‐western transect following the main road, in human‐modified outdoor habitats. Karyotypes of mice were determined using the yeast‐stimulated bone marrow cell method. Trapping sites were characterized in terms of their physical (altitude, temperature, precipitation and soil type) and habitat (human landscape use and occupancy) features. Demographic parameters of mouse populations, based on trapping‐with‐removal techniques, were also analysed (relative abundance, sex‐ratio, juvenile ratio and female fertility ratio), as well as body size (weight and length). Results Four chromosomal zones were identified on the basis of the frequency of two diagnostic rearrangements (Rb(6.7) in race E. Calheta and Rb(7.15) in race A. Cruz). E. Calheta was present in the two southern‐most zones, followed by the contact zone characterized by the presence of two inter‐racial hybrids and the co‐occurrence of mice belonging to the two races. The northern‐most part of the transect was occupied by A. Cruz. Environmental features differed leading us to split the transect into two parts. The southern part is characterized by lower altitude and precipitation, milder temperature, better soil quality supporting vegetable crops and vineyards, and more abundant and evenly distributed human habitats. This southern part is occupied by E. Calheta mice. The north‐western part presents characteristics opposite to those described above with cereals as the main cultivated crop, and it includes the contact zone as well as the zone inhabited by A. Cruz mice. The demographic parameters evaluated in this study did not differ significantly between chromosomal zones. Main conclusions This ecological survey highlights differences in climatic and edaphic features that have moulded the agricultural activities of humans, contributing to a differentiation of their spatial development, and hence the structure of potential habitats for mice. Results are interpreted within the source–sink framework of population dynamics, following which E. Calheta may function as a source and the areas where A. Cruz and the contact zone are located may function as a sink. Our study suggests that the position and chromosomal composition of the contact zone is influenced by the human component underlying broader environmental features. Similar characteristics were most likely present during the historical settlement of Madeira. They may have favoured the independent divergence of the two races and influenced the dynamics of the contact zone.     

The major histocompatibility complex and mating preferences in wild house mice (mus domesticus)

This study examined the relationship between the major histocompatibilitycomplex (MHC) genes and mate choice by wild house mice in acontrolled laboratory setting in an attempt to understand themechanisms maintaining natural MHC diversity. Three rearinggroups of wild test mice were produced: nonfostered controlmice, mice fostered into families of an inbred laboratory mousestrain, and mice fostered into families of a second mouse straindiffering genetically from the first only within the MHC region.At maturity, test mice were given a choice of two opposite-sexstimulus mice of the two MHC-congenic strains used for fostering.Test mice were scored for several measures of preference includingamount of time spent with either stimulus mouse, and ejaculationwith a stimulus mouse. Females in two of three rearing groupsspent more time with one MHC type regardless of rearing environment,suggesting that females did not prefer mates dissimilar fromfamily MHC type. Time preferences tended to be stronger in femalesthan in males. Male test mice ejaculated indiscriminantly. Femalewild mice mated to ejaculation more often in longer trials,but these matings were still too infrequent to assess preferences.Fostering had little or no effect on MHC-based mate preferencesof wild house mice, and no evidence suggested that MHC was usedto avoid inbreeding. Wild female mice may still choose matesbased on MHC haplotypes (but do not necessarily prefer MHC-dissimilarmates); other cues are probably also used. Based on these results,inbreeding avoidance does not seem a strong mechanism for maintainingnatural MHC diversity     

Gene flow and hybridization following introduction of Mus domesticus into an established population

Seventy-seven house mice ( Mus domesticus ) from Eday, Orkney were released into a long-established population on the Isle of May (56^o 12'N) in 1982. Introduced allozymes, mt and Y-chromosome DNA, and Robertsonian chromosomes spread rapidly, reaching approximate stability c . 3 years later at frequencies different to those in both parental populations. The hybrid population was morphometrically intermediate between the two parents. This is a preliminary summary only; full details will be published elsewhere.     

House mouse dispersal in Iron Age Spain: a geometric morphometrics appraisal

During the Iron Age, sea trade in the Mediterranean increased, particularly with the expansion of Phoenician and Greek colonies in the Western Mediterranean. A side effect of these human movements was the involuntary dispersion of commensal species, such as the house mouse (Mus musculus domesticus). One archaeological layer dated from the 4th Century BC, coming from an Iberian village located in the Mediterranean coast of Spain, contained a large and reliable accumulation of small mammals. The presence of the house mouse was highly suspected within this layer. To assess its abundance quantitatively, we used a geometric morphometrics approach of the first lower molar contour using elliptical Fourier analysis. We also increased the power of the discrimination between the Algerian mouse (Mus spretus) and the house mouse by combining a dimension reduction approach together with different validation procedures. The relative importance of age, sex, and geographical origin onto the shape and form of the lower molar contour was also investigated. The results obtained demonstrate the presence and the dominance of the house mouse in the landscape surrounding the Iberian village in the 1st Millennium BC, only a few centuries after its arrival in the Western Mediterranean Basin. A cross‐validated linear discriminant function considering different Mediterranean populations suggest Morocco and France as the most probable geographical origins for the Algerian mouse, and Tunisia for the origin of house mice in North‐Eastern Spain. © 2011 The Linnean Society of London, Biological Journal of the Linnean Society, 2011, 102 , 483–497.