Reduced recombination patterns in Robertsonian hybrids between chromosomal races of the house mouse: chiasma analyses.

The recombination suppression models of chromosomal speciation posit that chromosomal rearrangements act as partial barriers to gene flow allowing these regions to accumulate genetic incompatibilities, thus contributing to the divergence of populations. Empirical and theoretical studies exploring the requirements of these models have mostly focused on the role of inversions. Here, the recombination landscape of heterozygosity for Robertsonian (Rb) fusions is investigated in the house mouse. Laboratory-bred F1 males and females between highly differentiated races from Tunisia (Rb: 2n=22, Standard, St: 2n=40) were produced in which all Rb fusions are present as trivalents in meiosis. Recombination patterns were determined by the analysis of chiasmata and compared with previous data on the Tunisian parental mice. A comparative analysis was performed on wild-caught male mice spanning the hybrid zone between two Italian races (2n=40, 2n=22). The results showed that the chiasma characteristics of both male and female Tunisian F1 and Italian hybrids clearly differed from those of Rb and St mice. Not only was the mean chiasma number (CN) intermediate between those of the parental mice in both geographic samples, but the distribution of chiasmata along the chromosomal arms of the F1 showed a distinct mosaic pattern. In short, the proximal region in the F1 exhibited a reduced CN similar to that observed in homozygous Rb, whereas distal regions more closely matched those in St mice. These results suggest that Rb rearrangements (homozygous or heterozygous) reduce recombination in the proximal regions of the chromosomes supporting their potential role in recombination-mediated speciation models.

A new cytotype of the African pygmy mouse Mus minutoides in Eastern Africa. Implications for the evolution of sex-autosome translocations.

The African pygmy mice (genus Mus, subgenus Nannomys) are recognized for their highly conserved morphology but extensive chromosomal diversity, particularly involving sex-autosome translocations, one of the rarest chromosomal rearrangements among mammals. It has been shown that in the absence of unambiguous diagnostic morphological traits, sex-autosome translocations offer accurate taxonomic markers. For example, in Mus minutoides, irrespective of the diploid number (which ranges from 2n = 18 to 34), all specimens possess the sex-autosome translocations (X.1) and (Y.1) that are unique to this species. In this study, we describe a new cytotype that challenges this view. Males are characterized by the translocation (Y.1) only, while females carry no sex-autosome translocation, the X chromosome being acrocentric. Hence, although sex-autosome translocations (X.1) and (Y.1) are still diagnostic when one or both are present, their absence does not rule out M. minutoides. This cytotype has a large distribution, with specimens found in Tanzania and in the eastern part of South Africa. The nonpervasive distribution of Rb(X.1) provides an opportunity to investigate different evolutionary scenarios of sex-autosome translocations using a phylogenetic framework and the distribution of telomeric repeats. The results tend to support a scenario involving a reversal event, i.e., fusion then fission of Rb(X.1), and highlighted the existence of a new X1X1X2X2/X1X2Y sex chromosome system, confirming the remarkable diversity of neo-sex chromosomes and sex determination systems in the African pygmy mice.

Insights into the evolutionary history of the X-linked sex reversal mutation in mus minutoides: clues from sequence analyses of the Y-linked Sry gene.

The African pygmy mouse, Mus minutoides, is one of the very few mammal species that deviates from the classical mammalian XX/XY sex chromosome system by presenting a high proportion of fully fertile sex-reversed females. Since the still unknown sex reversal mutation is X-linked (X*), they are designated as X*Y females. Until now, X*Y females had only been identified in Southern Africa, but data were lacking for the rest of the vast sub-Saharan distribution range of this species. In this study, the PCR genotyping of the Y-linked Sry gene on 72 females from Western Africa (Guinea, Ivory Coast and Ghana) uncovered 10 sex-reversed females distributed in the 3 countries. This expands our understanding of the geographical distribution and temporal origin (dated at 0.9 mya) of the sex reversal mutation. In addition, we sequenced and analyzed a fragment of the Sry gene (including the complete high-mobility group, i.e. HMG box, and the partial C-terminal region). The results demonstrate the presence of multiple polymorphic copies of the gene as reported in other rodent species and reveal, more unexpectedly, an extremely high proportion of amino acid replacement within the HMG box. In effect, the predicted HMG box protein sequence similarity between some populations of M. minutoides is as low as 94.9%, and at the interspecific level (within genus), it drops to only 91.1% between M. minutoides and M. musculus.

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

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

Origin of the chromosomal radiation of Madeiran house mice: a microsatellite analysis of metacentric chromosomes.

Chromosome races of Mus musculus domesticus are characterised by particular sets of metacentric chromosomes formed by Robertsonian fusions and whole-arm reciprocal translocations. The Atlantic island of Madeira is inhabited by six chromosome races of house mice with 6-9 pairs of metacentric chromosomes. Three of these races are characterised by the metacentric 3.8 also found elsewhere in the distribution of M. m. domesticus, including Denmark and Spain. We investigated the possibility that metacentric 3.8 was introduced to Madeira during the initial colonisation, as this could have 'seeded' the cascade of chromosomal mutation that is the basis of the extraordinary chromosomal radiation observed on the island. Variation at 24 microsatellite loci mapping to three different chromosomal regions (proximal, interstitial and distal) of mouse chromosomes 3 and 8 was investigated in 179 mice from Madeira, Denmark, Portugal, Spain, Italy and Scotland. Analyses of microsatellite loci closely linked to the centromeres of these chromosomes ('proximal loci') do not support a common evolutionary origin of metacentric 3.8 among Madeiran, Danish and Spanish mouse populations. Our results suggest that Madeiran mice are genetically more similar to standard karyotype mice from Portugal than to metacentric mice from elsewhere. There is expected to be an interruption to gene flow between hybridising metacentric races on Madeira, particularly in the chromosomal regions close to the rearrangement breakpoints. Consistent with this, relating to differentiation involving chromosomes 3 and 8 on Madeira, we found greater genetic structure among races for proximal than interstitial or distal loci.

Chromosomal dynamics of nucleolar organizer regions (NORs) in the house mouse: micro-evolutionary insights.

Variation in the number and chromosomal location of nucleolar organizer regions (NORs) was studied in the house mouse, Mus musculus (2n=40). From an origin in Western Asia, this species colonized the Middle East, Europe and Asia. This expansion was accompanied by diversification into five subspecies. NOR diversity was revealed by fluorescence in situ hybridization using 18S and 28S probes on specimens spanning Asia to Western Europe. The results showed that the house mouse genome possessed a large number of NOR-bearing autosomes and a surprisingly high rate of polymorphism for the presence/absence of rRNA genes on all these chromosomes. All NOR sites were adjacent to the centromere except for two that were telomeric. Subspecific differentiation established from the NOR frequency data was concordant with the overall pattern of radiation proposed from molecular studies, but highlighted several discrepancies that need to be further addressed. NOR diversity in M. musculus consisted of a large number of polymorphic NORs that were common to at least two subspecies, and a smaller number of NORs that were unique to one subspecies. The most parsimonious scenario argues in favor of a subspecific differentiation by lineage sorting of ancestral NOR polymorphisms; only the unique NORs would have appeared by inter-chromosomal transposition, except for the two telomeric ones that may have originated by hybridization with another species. Such a scenario provides an alternative view from the one prevailing in most systematic and phylogenetic analyses that NORs have a high transposition rate due to concerted evolution of rRNA genes.

Fertility assessment in hybrids between monobrachially homologous Rb races of the house mouse from the island of Madeira: implications for modes of chromosomal evolution.

The speciation model of divergence by monobrachially homologous fusions (that is, with one arm in common) benefits from a wide conceptual acceptance, because heterozygotes between populations carrying such fusions suffer from high levels of meiotic dysfunction. The same meiotic configurations can also be generated by WART (whole-arm reciprocal translocation), rearrangements that are known to occur in mammals. Estimating the disadvantage of heterozygotes carrying monobrachially homologous fusions is required to evaluate the relevance of this mode of chromosomal evolution in diversification and speciation. House mice are an excellent study models because chromosomal races exist carrying monobrachially homologous fusions, and WARTs have been documented in this species. The fertility of heterozygote mice carrying the smallest number of monobrachially homologous fusions (that is, a chain of four chromosomes, C4) was investigated in laboratory-bred hybrids between two parapatric chromosomal races from the island of Madeira. Meiotic nondisjunction analyses and histological sections of testes showed that aneuploidy (16.7%) and germ cell death (50.9%) rates reached significantly higher mean values in hybrids than in homozygotes. In females, however, the histological analysis of ovarian follicle parameters revealed no significant differences between hybrid and homozygous individuals. Overall, the reproductive assays indicated that these C4-carrying hybrids were not sterile but showed an approximately 50% decrease in fertility compared to homozygous parental mice. Implications for modes of chromosomal evolution involving monobrachially homologous fusions are discussed.

Geographic patterns of inversion polymorphisms in a wild African rodent, Mastomys erythroleucus.

By suppressing recombination and reducing gene flow, chromosome inversions favor the capture and protection of advantageous allelic combinations, leading to adaptive polymorphisms. However, studies in non-model species remain scarce. Here we investigate the distribution of inversion polymorphisms in the multimammate rat Mastomys erythroleucus in West Africa. More than 270 individuals from 52 localities were karyotyped using G-bands and showed widespread polymorphisms involving four chromosome pairs. No significant deviations from Hardy-Weinberg equilibrium were observed either through space or time, nor were differences retrieved in viability or sex contribution between cytotypes. The distribution of chromosomal variation, however, showed perfect congruence with that of mtDNA-based phylogeographic clades. Thus, inversion diversity patterns in M. erythroleucus appeared more related to historical and/or demographic processes than to climate-based adaptive features. Using cross-species chromosome painting and G-banding analyses to identify homologous chromosomes in related out-group species, we proposed a phylogenetic scenario that involves ancestral-shared polymorphisms and subsequent lineage sorting during expansion/contraction of West African savannas. Our data suggest that long-standing inversion polymorphisms may act as regions in which adaptation genes may accumulate (nucleation model).

Molecular insights into the colonization and chromosomal diversification of Madeiran house mice.

The colonization history of Madeiran house mice was investigated by analysing the complete mitochondrial (mt) D-loop sequences of 156 mice from the island of Madeira and mainland Portugal, extending on previous studies. The numbers of mtDNA haplotypes from Madeira and mainland Portugal were substantially increased (17 and 14 new haplotypes respectively), and phylogenetic analysis confirmed the previously reported link between the Madeiran archipelago and northern Europe. Sequence analysis revealed the presence of four mtDNA lineages in mainland Portugal, of which one was particularly common and widespread (termed the 'Portugal Main Clade'). There was no support for population bottlenecks during the formation of the six Robertsonian chromosome races on the island of Madeira, and D-loop sequence variation was not found to be structured according to karyotype. The colonization time of the Madeiran archipelago by Mus musculus domesticus was approached using two molecular dating methods (mismatch distribution and Bayesian skyline plot). Time estimates based on D-loop sequence variation at mainland sites (including previously published data from France and Turkey) were evaluated in the context of the zooarchaeological record of M. m. domesticus. A range of values for mutation rate (mu) and number of mouse generations per year was considered in these analyses because of the uncertainty surrounding these two parameters. The colonization of Portugal and Madeira by house mice is discussed in the context of the best-supported parameter values. In keeping with recent studies, our results suggest that mutation rate estimates based on interspecific divergence lead to gross overestimates concerning the timing of recent within-species events.

Chromosomal phylogeny and evolution of the African mole-rats (Bathyergidae).

The subterranean African mole-rats (Family Bathyergidae) show considerable variation in their diploid numbers, but there is limited understanding of the events that shaped the extant karyotypes. Here we investigate chromosomal evolution in specimens representative of six genera and an outgroup species, the cane rat Thryonomys swinderianus, using flow-sorted painting probes isolated from the naked mole-rat, Heterocephalus glaber (2n = 60). A chromosomal phylogeny based on the cladistic analysis of adjacent syntenies detected by cross-species chromosome painting was not consistent with that obtained using DNA sequences due, in large part, to the conserved nature of the Bathyergus, Georychus and Cryptomys karyotypes. In marked contrast, the Fukomys and Heliophobius species showed extensive chromosome reshuffling, permitting their analysis by a computational approach that has conventionally been employed in comparative genomic studies for retrieving phylogenetic information based on DNA sequence or gene order data. Using the multiple genome rearrangements (MGR) algorithm and chromosomal rearrangement data detected among F. damarensis, F. darlingi, F. mechowi and the sister taxa B. janetta and Heliophobius argenteocinereus, cytogenetic support for the monophyly of Fukomys and a sister association for F. darlingi + F. damarensis was retrieved, mirroring the published sequence-based topology. We show that F. damarensis, a lineage adapted to arid and climatically unpredictable environments in Southern Africa, is characterized by a large number of fissions the fixation of which has probably been favoured by environmental factors and/or its particular eusocial structure.

Dissection of a Y-autosome translocation in Cryptomys hottentotus (Rodentia, Bathyergidae) and implications for the evolution of a meiotic sex chromosome chain.

We describe the outcome of a comprehensive cytogenetic survey of the common mole-rat, Cryptomys hottentotus, based on G and C banding, fluorescence in situ hybridisation and the analysis of meiotic chromosomes using immunostaining of proteins involved in the formation of synaptonemal complex (SCP1 and SCP3). We identified the presence of a Y-autosome translocation that is responsible for a fixed diploid number difference between males (2n = 53) and females (2n = 54), a character that likely defines the C. hottentotus lineage. Immunostaining, combined with C banding of spermatocytes, revealed a linearised sex trivalent with X(1) at one end and X(2) at the other, with evidence of reduced recombination between Y and X(2) that seems to be heterochromatin dependant in the C. hottentotus lineage. We suggest that this could depict the likely initial step in the differentiation of a true neo-X, and that this may mimic an early stage in the mammalian meiotic chain formation, an evolutionary process that has been taken to an extreme in a monotreme mammal, the platypus.

Patterns of genic diversity and structure in a species undergoing rapid chromosomal radiation: an allozyme analysis of house mice from the Madeira archipelago.

The chromosomal radiation of the house mouse in the island of Madeira most likely involved a human-mediated colonization event followed by within-island geographical isolation and recurrent episodes of genetic drift. The genetic signature of such processes was assessed by an allozyme analysis of the chromosomal races from Madeira. No trace of a decrease in diversity was observed suggesting the possibility of large founder or bottleneck sizes, multiple introductions and/or a high post-colonization expansion rate. The Madeira populations were more closely related to those of Portugal than to other continental regions, in agreement with the documented human colonization of the island. Such a Portuguese origin contrasts with a study indicating a north European source of the mitochondrial haplotypes present in the Madeira mice. This apparent discrepancy may be resolved if not one but two colonization events took place, an initial north European introduction followed by a later one from Portugal. Asymmetrical reproduction between these mice would have resulted in a maternal north European signature with a nuclear Portuguese genome. The extensive chromosomal divergence of the races in Madeira is expected to contribute to their genic divergence. However, there was no significant correlation between chromosomal and allozyme distances. This low apparent chromosomal impact on genic differentiation may be related to the short time since the onset of karyotypic divergence, as the strength of the chromosomal barrier will become significant only at later stages.

Complex evolution of X and Y autosomal translocations in the giant mole-rat, Cryptomys mechowi (Bathyergidae).

Cross-species chromosome painting was used to determine homologous chromosomal regions between two species of mole-rat, the naked mole-rat, Heterocephalus glaber (2n = 60), and the giant mole-rat, Cryptomys mechowi (2n = 40), using flow-sorted painting probes representative of all but two of the H. glaber chromosomal complement. In total 43 homologous regions were identified in the C. mechowi genome. Eight H. glaber chromosomes are retained in toto in C. mechowi, and 13 produce two or more signals in this species. The most striking difference in the karyotypes of the two taxa concerns their sex chromosomes. The H. glaber painting probes identified a complex series of translocations that involved the fractionation of four autosomes and the subsequent translocation of segments to the sex chromosomes and to autosomal partners in the C. mechowi genome. An intercalary heterochromatic block (IHB) was detected in sex chromosomes of C. mechowi at the boundary with the translocated autosomal segment. We discuss the likely sequence of evolutionary events that has led to the contemporary composition of the C. mechowi sex chromosomes, and consider these in the light of prevailing views on the genesis of sex chromosomes in mammals.

Adaptive energetics in house mice, Mus musculus domesticus, from the island of Porto Santo (Madeira archipelago, North Atlantic).

The bioenergetic strategies of house mice (Mus musculus domesticus) from the island of Porto Santo were investigated and compared with those of mice from mainland Portugal. Energy obtained from food ingestion was 18.2% lower in Porto Santo mice than in mainland mice (1.53 vs. 1.87 kJ/g/day). The same pattern was observed for metabolisable energy intake, which was 19.2% lower in island specimens (0.87 vs. 1.08 kJ/g/day for mainland specimens). Apparent digestibility was similar in both groups of mice. Basal metabolic rate (BMR) of Porto Santo individuals was low (1.16 ml O(2)/g/h), representing only 56% of the predicted value, based on body mass, while mainland individuals exhibited a BMR closer to the expected value, corresponding to 87% of the predicted value (1.80 ml O(2)/g/h). Thermoregulatory abilities within the range of 10-28 degrees C ambient temperature did not differ between island and mainland mice. Results suggest an adaptation of Porto Santo mice to the environmental aridity of the island of Porto Santo, leading to a conservative energetic strategy.

Chromosomal and allozyme analysis of a hybrid zone between parapatric Robertsonian races of the house mouse: a case of monobrachial homology.

A detailed chromosomal and allozyme analysis of Robertsonian (Rb) populations of the house mouse in Alsace (France) was performed to evaluate the model of speciation by monobrachial centric fusions. The karyological analysis confirmed the existence of a hybrid zone between two Rb races differentiated by monobrachially homologous Rb fusions. The clinical distribution of Rb fusions showed that almost no overlap occurred between the Rb fusions specific to each race, indicating the presence of an acrocentric peak in the center of the hybrid zone. Thus, only chromosomal heterozygotes carrying one to three trivalents were present, instead of the expected highly unfit interracial hybrids, none of which were observed. The effect of karyotypic differentiation on genic divergence was tested across the hybrid zone by comparing levels of genetic structure for chromosomal and allozyme markers according to the isolation by distance model. Results confirmed the highly significant spatial structure for chromosomes, but revealed none for allozymes, indicating that genic diversity was not structured according to karyotype. These data suggest the absence of a strong chromosomal barrier to gene flow, which does not conform with predictions of the model of speciation by monobrachial centric fusions. In addition, the relatedness of these Rb races to neighboring ones, as well as the nonrandom contribution of several chromosomes to the Rb fusions, was analyzed.

Chromosomal characterization of Arvicanthis species (Rodentia, Murinae) from western and central Africa: implications for taxonomy.

A chromosome study of unstriped grass rats of the genus Arvicanthis (Rodentia, Murinae) in western and central Africa is presented. The observations extend the data available to 242 specimens from 59 localities. All individuals karyotyped belong to four karyotypic forms, or cytotypes, earlier described as ANI-1, ANI-2, ANI-3, and ANI-4 and are presumed to correspond to four distinct species. In order to provide diagnostic characters for these western and one central African Arvicanthis species, we standardized the chromosomal data available and developed a G- and C-banded chromosome nomenclature that allows easy species identification. Each form is characterized by a distinct geographical distribution, roughly following the biogeographical domains of western Africa, although their precise limits remain to be assessed. The sole area of sympatry detected is the region of the inner delta of the Niger River, where both ANI-1 and ANI-3 can be found. It is proposed that the three western African species ANI-1, ANI-3, and ANI-4 be renamed as A. niloticus, A. ansorgei, and A. rufinus, respectively.

Molecular studies on the colonization of the Madeiran archipelago by house mice.

To study the colonization history of the house mouse (Mus musculus domesticus) on the Madeiran archipelago, complete mitochondrial D-loop sequences were obtained for 44 individuals from Madeira, Porto Santo and Ilhas Desertas. Altogether, 19 D-loop haplotypes were identified which formed part of a single clade in a phylogeny incorporating haplotypes from elsewhere in the range of M. m. domesticus, indicating that the Madeiras were colonized from a single source. Similarities between the sequences found in the Madeiras and those in Scandinavia and northern Germany suggest that northern Europe was the source area, and there is the intriguing possibility that the Vikings may have accidentally brought house mice to the archipelago. However, there is no record of Vikings visiting the Madeiras; on historical grounds, Portugal is the most likely source area for Madeiran mice and further molecular data from Portugal are needed to rule out that possibility.

Developmental stability in house mice heterozygous for single Robertsonian fusions.

Fluctuating asymmetry (FA) of tooth traits has been reported to be increased in Down syndrome patients as well as hybrids between chromosomal races of the house mouse differing in several Robertsonian (Rb) fusions. Developmental stability, assessed by FA, is thus thought to be impaired by spontaneous chromosomal abnormality or by chromosomal heterozygosity. Although the effect of a single fusion on developmental stability could theoretically be expected, it has never been documented. Crosses involving two chromosomal races of the house mouse diverging for one Rb fusion were performed to assess developmental stability in parental homozygous races as well as in their hybrids. Moreover, the occurrence of a spontaneous chromosomal mutation (WART type-b) allowed us to study the instantaneous effect of such a translocation on developmental stability. No difference in fluctuating asymmetry levels was detected among the groups considered in this study. This result suggested that a single stable or spontaneous balanced structural rearrangement did not inherently disturb developmental stability. In addition, the differential effect on developmental stability of one versus many heterozygous Rb fusions highlights the role of their quantitative accumulation in the disruption of coadaptation in chromosomal hybrids.

[Probable origin of the Robertsonian phenomena in domestic mice in Tunisia]. / Origine probable du phénomène Robertsonien chez la souris domestique de Tunisie.

The Robertsonian phenomenon in house mice (Mus musculus domesticus) from Tunisia consists in the presence of only one 22-chromosome Robertsonian race (22Rb) carrying the maximum number of fusions observed until now. The 22Rb populations exclusively occupy urban centers in the Eastern-Central region of Tunisia where standard population with 40-all acrocentric chromosomes (40Std) occur in surrounding neighborhoods and rural environments. In addition to the habitat partition, allozyme and mitochondrial DNA analyses showed that the 22Rb populations were genetically differentiated from the 40Std ones. This differentiation mostly stemmed from an important decrease in genetic variability in the 22Rb populations from the Sahel towns. The extent of morphological, ecological and genetical divergence observed between these chromosomal races in Tunisia is in agreement with the predictions of the chromosomal speciation model of White which advocates that karyotypic differentiation between taxa can lead to their reproductive isolation and independent evolution. Such a process is verified if the Rb process in Tunisia results from local differentiation which is supported by both the genetic and morphological data. However, the hypothesis of an origin by introduction of these mice from another region of Tunisia or from another country cannot be totally dismissed. In this study, an allozymic analysis of mice (22Rb and 40Std) from the geographically distant city of Kairouan was performed. Results showed that 22Rb and 40Std mice from Kairouan shared the same high degree of variability, and were not genetically differentiated. This contrasts with the results registered in the two chromosomal races in the Sahel towns. Such data argue in favor of a local differentiation of the Robertsonian process in Tunisia and suggest that the decrease in variability of the structural nuclear genes in the Sahel 22Rb populations can be related to an introduction from Kairouan into a Sahel locality resulting in a founder effect or followed by a severe bottleneck prior to its dispersion throughout the Sahel region.

Spontaneous occurrence of a Robertsonian fusion involving chromosome 19 by single whole-arm reciprocal translocation (WART) in wild-derived house mice.

Chromosomal races of the house mouse (Mus musculus domesticus) bear Robertsonian (Rb) fusions, which consist of centric translocations between two non-homologous acrocentric chromosomes. The high level of diversity of these fusions in house mice is generated by de-novo formation of Rb fusions and subsequent whole-arm reciprocal exchanges (WARTs). This paper describes the spontaneous occurrence of a new Rb fusion, Rb(4.19), in progeny of wild-derived house mice segregating for Rb(4.12). The chromosomal mutation was traced to a female which exhibited germline and somatic mosaicism indicating an early embryonic origin of the mutation. FISH analysis of centromerically-located ribosomal genes suggested that no modification was observed on chromosomes 12 and 19 prior to or following the occurrence of Rb(4.19). Distribution of telomeric sequences showed that both Rb fusions lacked telomeres in their centromeric regions. It is argued that this spontaneous mutation most likely originated by single whole-arm reciprocal translocation (WART) between Rb(4.12) and an acrocentric chromosome 19, resulting in Rb(4.19) and a neo-acrocentric chromosome 12. Sequences required for centromeric function and proximal telomeres would have been transferred to the neo-chromosome 12 from chromosome 19 during the translocation. The existence of such WARTs which generate derived acrocentric chromosomes has several implications for chromosomal evolution in house mice.