Studies on the Robertsonian chromosomal variation of Mus musculus domesticus (Rodentia, Muridae) in Greece

The karyotype of the house mouse, Mus musculus domesticus , was examined in 282 specimens from 44 localities, in an effort to gain better understanding of the Robertsonian (Rb) variation known to exist in Greece. We consider that an Rb system exists in Peloponnisos, southern Greece, distributed in an area that is substantially larger than previously known. It consists of at least three Rb races with 2 n  = 30, 2 n  = 24 and 2 n  = 28, respectively, the last being reported for the first time in this paper and carrying Rb(3.6), Rb(8.12), Rb(10.14), Rb(13.15), Rb(9.16) and Rb(11.17) in a homozygous state. Additional instances of variation in this Rb system include individuals with 2 n  = 31 and 32 of variable Rb constitution and hybrids between the Rb races with 2 n  = 30 and 2 n  = 24. In southern Peloponnisos, Rb(10.14) was found in either a homozygous or a heterozygous state (2 n  = 38 or 39). The relationships among the Rb populations of Peloponnisos are discussed and hypotheses for their evolution are proposed. Rb variation was also recorded in two new locations of eastern Sterea Ellas (2 n  = 28 and 29) and one in Ipiros, north-west Greece (2 n  = 38). These findings corroborate the existence of two separate Rb systems in those two areas. Moreover, among a number of islands surveyed, Rb variation was only found in Kythira island, with Rb(10.14) in a heterozygous state (2 n  = 39). Finally, the typical all-acrocentric karyotype (2 n  = 40) was found in 51 of the animals studied from 13 localities. © 2005 The Linnean Society of London, Biological Journal of the Linnean Society , 2005, 84 , 503–513.     

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.     

Mitochondrial DNA in the hybrid zone between Mus musculus musculus and Mus musculus domesticus: a comparison of two transects

We studied mtDNA introgression across the contact zone between Mus musculus musculus and M. m. domesticus in two independent transects in the Czech Republic and Bavaria, Germany. A total of 1270 mice from 98 localities in the Czech transect and 456 mice from 41 localities in the Bavarian transect were examined for presence or absence of a Bam HI restriction site in the mt-Nd1 gene. Using this simple mtDNA marker, variants that belonged to the M. m. domesticus lineage (presence of restriction site) could be unequivocally distinguished from those belonging to the M. m. musculus lineage (absence of restriction site). The extent of introgression of mtDNA, three autosomal allozymes and the X chromosome was compared. The introgression of X markers was more limited than was that of the allozymes and mtDNA. In the Czech transect, the centre for the mtDNA cline was shifted about 3.6 km to the west relative to the X chromosome cline, with asymmetric introgression from M. m. musculus to M. m. domesticus . Interestingly, in the Bavarian transect, the centre of the mtDNA cline was shifted about 10.9 km to the east relative to the X chromosome cline, with asymmetric introgression from M. m. domesticus to M. m. musculus, opposite in direction to that observed in the Czech transect.  © 2005 The Linnean Society of London, Biological Journal of the Linnean Society , 2005, 84 , 363–378.     

Evolutionary modularity of the mouse mandible: dissecting the effect of chromosomal reorganizations and isolation by distance in a Robertsonian system of Mus musculus domesticus

The mouse mandible consists of several morphogenetic units that are usually grouped into two main modules: the alveolar region and the ascending ramus. The genetic/ontogenetic modularity of the two regions implies that they might evolve independently to some extent. In particular, evolutionary modularity in quantitative traits could arise during chromosomal speciation due to lower gene flow in rearranged chromosomes. With the aim of uncovering the autonomous evolution of the mandible modules, the form variation of each of them was assessed in the house mouse Robertsonian system from Barcelona, in which chromosomal variation and geographical distance may act as isolation factors. The association between these factors and morphological changes was analysed to determine their contribution to the differentiation of each module. Although size changes in the two modules were highly correlated, shape changes were not, and their association with karyotype differences, but not geographical distance, was dependent on the module. The results support the existence of two evolutionary modules and highlight the importance of size in morphological integration of the mandible. They also suggest that geographical distance and chromosomal reorganizations reduce gene flow between karyotypically divergent populations, but although geographical distance represents a global barrier to gene flow, the isolation produced by a set of chromosomal reorganizations only affects particular modules, probably depending on the number and location of loci with effects on a particular morphological region.     

Mitochondrial DNA variation in the western house mouse (Mus musculus domesticus) close to its site of origin: studies in Turkey

In contrast to a substantial inventory of mitochondrial d -loop sequences from the West European part of the range of the western house mouse Mus musculus domesticus , there are few such data from close to the Middle Eastern origin of the subspecies. This paper attempts to rectify this situation, with details of d -loop sequences of 92 mice from 45 localities in Turkey, adding to the six mice from three localities previously studied from that country. The molecular data were found to be consistent with Turkey being close to the site of origin of M. m. domesticus . The 54 Turkish haplotypes were distributed throughout a phylogenetic tree incorporating representative sequences described previously, and there was high nucleotide diversity among the Turkish mice. There was weak genetic structure in Turkey, although haplotypes of the 'Main Turkish Clade', while common over much of Turkey, were absent from Southern Anatolia. Haplotypes of the Main Turkish Clade were also found in western Europe and it is believed that they derived from Turkey, which thus represents one of the source areas for the westwards expansion of M. m. domesticus .  © 2005 The Linnean Society of London, Biological Journal of the Linnean Society , 2005, 84 , 473–485.     

The genomics of speciation: investigating the molecular correlates of X chromosome introgression across the hybrid zone between Mus domesticus and Mus musculus

Understanding the genetic details of reproductive isolation is a key goal in the study of speciation. Hybrid zones, geographical regions where two species meet and exchange genes, can provide insight into the genetic basis of reproductive isolation. This is especially true in species with mapped molecular markers because patterns of gene flow can be compared among different genomic regions. Even greater insight can be obtained in species with complete genome sequences because gene identity, gene number and other features of interest can be assessed for genomic regions with different patterns of introgression. Here, we review recent studies on the well-characterized hybrid zone between Mus domesticus and M. musculus , including a detailed survey of patterns of introgression for 13 markers on the X chromosome. We then compare levels of introgression for these 13 regions to a number of genomic attributes inferred from the complete sequence of the X chromosome, with two purposes. First, we identify candidate genes for reproductive isolation by finding genes that map to an X-linked region of reduced introgression and that are only expressed in the male germ line or that show high rates of protein evolution in comparison with rat. Second, we ask whether patterns of gene flow are correlated with recombination rate, gene density, base composition, CpG island density, mutation rate and the rate of protein evolution, as might be expected if many genes contribute to reproductive isolation. We identify seven candidate genes for reproductive isolation between M. domesticus and M. musculus , and our analyses reveal no general correlations between levels of introgression and other measured sequence characteristics. These results underline the utility of the house mouse as a model system for the study of speciation.  © 2005 The Linnean Society of London, Biological Journal of the Linnean Society , 2005, 84 , 523–534.     

Reproductive isolation between chromosomal races of the house mouse Mus musculus domesticus in a parapatric contact area revealed by an analysis of multiple unlinked loci

The house mouse, Mus musculus domesticus, exhibits a high level of chromosomal polymorphism because of the occurrence and fast fixation of Robertsonian fusions between telocentric chromosomes. For this reason, it has been considered a classical speciation model to analyse the role of the chromosomal changes in reproductive isolation. In this study, we analysed a parapatric contact area between two metacentric races in central Italy, the Cittaducale race (CD: 2n = 22) and the Ancarano race (ACR: 2n = 24), to estimate gene flow at the boundary. Hybrids between these two races show high levels of structural heterozygosity and are expected to be highly infertile. A sample of 88 mice from 14 sites was used. The mice were genotyped by means of eight microsatellite loci mapped in four different autosomal arms. The results show clear genetic differentiation between the CD and ACR races, as revealed by differences in allele frequencies, factorial correspondence analysis and indexes of genetic population (e.g. F(ST) and R(ST)) along the contact zone. The genetic differentiation between the races was further highlighted by assignation and clustering analyses, in which all the individuals were correctly assigned by their genotypes to the source chromosomal race. This result is particularly interesting in view of the absence of any geographical or ecological barrier in the parapatric contact zone, which occurs within a village. In these conditions, the observed genetic separation suggests an absence of gene flow between the races. The CD-ACR contact area is a rare example of a final stage of speciation between chromosomal races of rodents because of their chromosomal incompatibility.     

On the origin of Robertsonian fusions in nature: evidence of telomere shortening in wild house mice

The role of telomere shortening to explain the occurrence of Robertsonian (Rb) fusions, as well as the importance of the average telomere length vs. the proportion of short telomeres, especially in nature populations, is largely unexplored. In this study, we have analysed telomere shortening in nine wild house mice from the Barcelona Rb system with diploid numbers ranging from 29 to 40 chromosomes. We also included two standard (2n = 40) laboratory mice for comparison. Our data showed that the average telomere length (considering all chromosomal arms) is influenced by both the diploid number and the origin of the mice (wild vs. laboratory). In detail, we detected that wild mice from the Rb Barcelona system (fused and standard) present shorter telomeres than standard laboratory mice. However, only wild mice with Rb fusions showed a high proportion of short telomeres (only in p‐arms), thus revealing the importance of telomere shortening in the origin of the Rb fusions in the Barcelona system. Overall, our study confirms that the number of critically short telomeres, and not a simple reduction in the average telomere length, is more likely to lead to the origin of Rb fusions in the Barcelona system and ultimately in nature.     

Phylogenetic analysis of the distribution of chromosomal races of Mus mnscuius domesticus Rutty in Europe

Robertsonian (Rb) translocation is a common chromosomal rearrangement in the house mouse. In free-living populations, 79 fusions with different combinations of chromosomes 1 to 18 have been found in some 45 populations. An updated list of these fusions is presented and analysed in order to reveal the possible processes by which the fusions spread within or among populations. A widespread hypothesis is that when two populations share the same fusion, it can be assumed that they have a common ancestor. This can serve as the basis for the use of the cladistic methods. While I present such an analysis on the updated list of Rbs, I also point to the problems associated with it in this case because many fusions have multiple origins and exchanges of Rbs between populations are frequent. I have tried to use a different approach, based on a critical and quantitative evaluation of the hypothesis of common ancestry. Assuming that the 153 possible fusions have an equal probability of occurrence, I give the formula to compute the probability that populations share a given number of fusions by chance alone. Only when this probability is lower than a chosen level (say 5%) can the populations be inferred to have a non-independent origin (i.e. they have a common ancestor or they have exchanged chromosomes by introgression). This probability measure is then used as a distance estimate to show the relationship between all the Rb populations. This analysis suggests that although some Rbs must have occurred more than once, most of the populations have non-independent origins. Almost all the populations from northern Africa to Belgium and Germany appear to have close karyotopic relationships and form a major group. Clearly independent Rb populations are mainly found in the periphery of this major group, for example in Scotland, Denmark and Spain. 'Chromosomal' flow between Rb populations appears to be a very important process.     

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.     

High diversity of centric fusions with monobrachial homology in an area of chromosomal polymorphism of Mus musculus domesticus

One of the simplest models of chromosomal speciation is speciation by monobrachial centric fusion. This model is based on the assumption that a sterility barrier can develop between populations, in which fixed centric fusions show monobrachial homology, i.e. share only one chromosome arm. However, studies aimed at delineating intermediate stages of transition to reproductive isolation are lacking. In this paper, we describe a new area of chromosomal polymorphism in the house mouse, Mus musculus domesticus Schwarz and Schwarx, 1943, in Sicily (Italy). We trapped 79 mice at eighteen localities in an area of approximately 500 Km² surrounding the largest active European volcano, Mount Etna. Combining G‐banding and chromosome painting we identified twelve different Robertsonian (Rb) metacentrics. Considering the high number of Rb fusions, some of them shared with other documented areas, the presently studied area of chromosomal polymorphism is very likely to represent a mixture of allochthonous and autochthonous Rb fusions. The Rb(9.16) is the most widespread metacentric (overall frequency 0.80). Two Rb metacentrics, Rb(4.10) and Rb(5.6), have similar overall frequency, 0.29 and 0.37, respectively, and are narrowly co‐distributed in ten populations. Nine fusions – Rb(2.13), Rb(1.3), Rb(12.17), Rb(8.17), Rb(2.14), Rb(10.14), Rb(11.17), Rb(3.15), and Rb(11.14) – show a low frequency (0.04–0.01) and mostly non‐overlapping localization, but each of them shares monobrachial homology with at least one other metacentric. The overall geographical distribution of different Rb fusions seems to match an early stage of race formation. The eventual role of the presently studied hybrid zone in the context of chromosomal speciation by monobrachial centric fusions is discussed. © 2011 The Linnean Society of London, Biological Journal of the Linnean Society, 2011, 103 , 722–731.     

Chromosomal rearrangements,phenotypic variation and modularity: a case study from a contact zone between house mouse Robertsonian races in Central Italy

The Western European house mouse, Mus musculus domesticus, is well‐known for the high frequency of Robertsonian fusions that have rapidly produced more than 50 karyotipic races, making it an ideal model for studying the mechanisms of chromosomal speciation. The mouse mandible is one of the traits studied most intensively to investigate the effect of Robertsonian fusions on phenotypic variation within and between populations. This complex bone structure has also been widely used to study the level of integration between different morphogenetic units. Here, with the aim of testing the effect of different karyotypic assets on the morphology of the mouse mandible and on its level of modularity, we performed morphometric analyses of mice from a contact area between two highly metacentric races in Central Italy. We found no difference in size, while the mandible shape was found to be different between the two Robertsonian races, even after accounting for the genetic relationships among individuals and geographic proximity. Our results support the existence of two modules that indicate a certain degree of evolutionary independence, but no difference in the strength of modularity between chromosomal races. Moreover, the ascending ramus showed more pronounced interpopulation/race phenotypic differences than the alveolar region, an effect that could be associated to their different polygenic architecture. This study suggests that chromosomal rearrangements play a role in the house mouse phenotypic divergence, and that the two modules of the mouse mandible are differentially affected by environmental factors and genetic makeup.     

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.     

Evolution of the chromosomal races of Mus musculus domesticus in the Rhaetian Alps: the roles of whole-arm reciprocal translocation and zonal raciation

The evolution of ten Robertsonian (Rb) races of the house mouse (Mus musculus domesticus) in the Rhaetian Alps of northern Italy and southern Switzerland is reconsidered. The mechanisms of centric fusion, zonal raciation and, for the first time, whole-arm reciprocal translocation (WART), are used in this non-mathematical approach to produce a phylogenetic tree (using chromosome fusions as characters) with the smallest number of steps. The shortest tree that we found (16 steps) is at least two to nine mutations shorter than previously published models. Three other trees (17 or 18 steps) are also considered, since they are geographically more sensible. In general, these four scenarios correspond more closely to the present distributions of the ten Rb races than previous trees. Our results suggest that zonal raciation and WARTs play an important role in the evolution of Rb races of the house mouse.     

Chromosomal evolution of the house mouse, Mus musculus domesticus, in the Aeolian Archipelago (Sicily, Italy)

We describe the chromosomal evolution of the metacentric populations of the house mouse, Mus musculus domesticus , which constitute the Robertsonian System of Aeolian Islands (Sicily, Italy). Eighty-nine specimens from all the seven islands that form the Archipelago were cytogenetically examined. The analysis shows the presence of 4 Rb races with a large number of shared metacentric chromosomes: 2 n  = 36 on Panarea, 2 n  = 34 on Alicudi, 2 n  = 26 on Lipari and Stromboli, and a different 2 n  = 26 race on Vulcano. On Salina and Filicudi, the standard karyotype was found. Polymorphism was only found in a population on Panarea Island and this population shares no metacentrics with the other races. The distribution of metacentrics among the races and the comparison between the Aeolian metacentrics and those found in the 97 previously documented metacentric populations allows us to formulate a hypothesis of chromosomal evolution for the Aeolian Robertsonian system. Six of the twelve metacentric chromosomes found in the Aeolian Islands come from localities outside the archipelago. The evolutionary model highlights how the chromosomal races originated inside the Archipelago and involve several factors, such as formation in situ of metacentrics, zonal raciation and, whole arm reciprocal translocation. © 2009 The Linnean Society of London, Biological Journal of the Linnean Society , 2009, 96 , 194–202.     

A multilocus perspective on refugial isolation and divergence in rainforest skinks (Carlia)

To explore the evolutionary consequences of climate-induced fluctuations in distribution of rainforest habitat we contrasted demographic histories of divergence among three lineages of Australian rainforest endemic skinks. The red-throated rainbow skink, Carlia rubrigularis, consists of morphologically indistinguishable northern and southern mitochondrial DNA (mtDNA) lineages that are partially reproductively isolated at their parapatric boundary. The third lineage (C. rhomboidalis) inhabits rainforests just to the south of C. rubrigularis, has blue, rather than red-throated males, and for mtDNA is more closely related to southern C. rubrigularis than is northern C. rubrigularis. Multigene coalescent analyses supported more recent divergence between morphologically distinct lineages than between morphologically conservative lineages. There was effectively no migration and therefore stronger isolation between southern C. rubrigularis and C. rhomboidalis, and low unidirectional migration between morphologically conservative lineages of C. rubrigularis. We found little or no evidence for strong differences in effective population size, and hence different contributions of genetic drift in the demographic history of the three lineages. Overall the results suggest contrasting responses to long-term fluctuations in rainforest habitats, leading to varying opportunities for speciation.     

Mitochondrial DNA polymorphisms of the house mouse Mus musculus domesticus from Greece, focusing on the Robertsonian chromosomal system of north-west Peloponnese

This study focused on the sequence variation in a mitochondrial region in house mice Mus musculus domesticus from chromosomally variable populations in the north-west Peloponnese, Greece. The mitochondrial molecular variation revealed was among the highest found so far for M. m. domesticus populations. The haplotype distribution pattern was rather complex. There was no clear differentiation between the populations characterized by Robertsonian chromosomes and standard all-acrocentric populations. There is therefore no indication that the Robertsonian populations were formed during a prolonged period of geographical isolation.  © 2005 The Linnean Society of London, Biological Journal of the Linnean Society , 2005, 84 , 643–651.     

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.     

Evolutionary and dispersal history of Eurasian house mice Mus musculus clarified by more extensive geographic sampling of mitochondrial DNA

We examined the sequence variation of mitochondrial DNA control region and cytochrome b gene of the house mouse (Mus musculus sensu lato) drawn from ca. 200 localities, with 286 new samples drawn primarily from previously unsampled portions of their Eurasian distribution and with the objective of further clarifying evolutionary episodes of this species before and after the onset of human-mediated long-distance dispersals. Phylogenetic analysis of the expanded data detected five equally distinct clades, with geographic ranges of northern Eurasia (musculus, MUS), India and Southeast Asia (castaneus, CAS), Nepal (unspecified, NEP), western Europe (domesticus, DOM) and Yemen (gentilulus). Our results confirm previous suggestions of Southwestern Asia as the likely place of origin of M. musculus and the region of Iran, Afghanistan, Pakistan, and northern India, specifically as the ancestral homeland of CAS. The divergence of the subspecies lineages and of internal sublineage differentiation within CAS were estimated to be 0.37–0.47 and 0.14–0.23 million years ago (mya), respectively, assuming a split of M. musculus and Mus spretus at 1.7 mya. Of the four CAS sublineages detected, only one extends to eastern parts of India, Southeast Asia, Indonesia, Philippines, South China, Northeast China, Primorye, Sakhalin and Japan, implying a dramatic range expansion of CAS out of its homeland during an evolutionary short time, perhaps associated with the spread of agricultural practices. Multiple and non-coincident eastward dispersal events of MUS sublineages to distant geographic areas, such as northern China, Russia and Korea, are inferred, with the possibility of several different routes.