Multiple Genomic Landscapes of Recombination and Genomic Divergence in Wild Populations of House Mice-The Role of Chromosomal Fusions and Prdm9.

Chromosomal fusions represent one of the most common types of chromosomal rearrangements found in nature. Yet, their role in shaping the genomic landscape of recombination and hence genome evolution remains largely unexplored. Here, we take advantage of wild mice populations with chromosomal fusions to evaluate the effect of this type of structural variant on genomic landscapes of recombination and divergence. To this aim, we combined cytological analysis of meiotic crossovers in primary spermatocytes with inferred analysis of recombination rates based on linkage disequilibrium using single nucleotide polymorphisms. Our results suggest the presence of a combined effect of Robertsonian fusions and Prdm9 allelic background, a gene involved in the formation of meiotic double strand breaks and postzygotic reproductive isolation, in reshaping genomic landscapes of recombination. We detected a chromosomal redistribution of meiotic recombination toward telomeric regions in metacentric chromosomes in mice with Robertsonian fusions when compared to nonfused mice. This repatterning was accompanied by increased levels of crossover interference and reduced levels of estimated recombination rates between populations, together with high levels of genomic divergence. Interestingly, we detected that Prdm9 allelic background was a major determinant of recombination rates at the population level, whereas Robertsonian fusions showed limited effects, restricted to centromeric regions of fused chromosomes. Altogether, our results provide new insights into the effect of Robertsonian fusions and Prdm9 background on meiotic recombination.

PRDM9 Diversity at Fine Geographical Scale Reveals Contrasting Evolutionary Patterns and Functional Constraints in Natural Populations of House Mice.

One of the major challenges in evolutionary biology is the identification of the genetic basis of postzygotic reproductive isolation. Given its pivotal role in this process, here we explore the drivers that may account for the evolutionary dynamics of the PRDM9 gene between continental and island systems of chromosomal variation in house mice. Using a data set of nearly 400 wild-caught mice of Robertsonian systems, we identify the extent of PRDM9 diversity in natural house mouse populations, determine the phylogeography of PRDM9 at a local and global scale based on a new measure of pairwise genetic divergence, and analyze selective constraints. We find 57 newly described PRDM9 variants, this diversity being especially high on Madeira Island, a result that is contrary to the expectations of reduced variation for island populations. Our analysis suggest that the PRDM9 allelic variability observed in Madeira mice might be influenced by the presence of distinct chromosomal fusions resulting from a complex pattern of introgression or multiple colonization events onto the island. Importantly, we detect a significant reduction in the proportion of PRDM9 heterozygotes in Robertsonian mice, which showed a high degree of similarity in the amino acids responsible for protein-DNA binding. Our results suggest that despite the rapid evolution of PRDM9 and the variability detected in natural populations, functional constraints could facilitate the accumulation of allelic combinations that maintain recombination hotspot symmetry. We anticipate that our study will provide the basis for examining the role of different PRDM9 genetic backgrounds in reproductive isolation in natural populations.

Population effects of heavy metal pollution in wild Algerian mice (Mus spretus).

Heavy metal mining is one of the largest sources of environmental pollution. The analysis of different types of biomarkers in sentinel species living in contaminated areas provides a measure of the degree of the ecological impact of pollution and is thus a valuable tool for human and environmental risk assessments. In previous studies we found that specimens from two populations of the Algerian mice (Mus spretus) living in two abandoned heavy metal mines (Aljustrel and Preguiça, Portugal) had higher body burdens of heavy metals, which led to alterations in enzymatic activities and in haematological, histological and genotoxic parameters, than mice from a nearby reference population. We have now analysed individuals from the same sites at the biometric and genetic levels to get a broader portrayal of the impact of heavy metal pollution on biodiversity, from molecules to populations. Size and shape variations of the mouse mandible were searched by implementing the geometric morphometric method. Population genetic differentiation and diversity parameters (φST estimates; nucleotide and haplotype diversities) were studied using the mitochondrial cytochrome b gene (Cytb) and the control region (CR). The morphometric analyses revealed that animals from the three sites differed significantly in the shape of the mandible, but mandibular shape varied in a more resembling way within individuals of both mine sites, which is highly suggestive for an effect of environmental quality on normal development pathways in Algerian mice. Also, antisymmetry in mandible size and shape was detected in all populations, making these traits not reliable indicators of developmental instability. Overall little genetic differentiation was found among the three populations, although pairwise φST comparisons revealed that the Aljustrel and the Preguiça populations were each differentiated from the other two populations in Cytb and in CR, respectively. Genetic diversity parameters revealed higher genetic diversity for Cytb in the population from Aljustrel, while in the population from Preguiça diversity of the two markers changed in opposite directions, higher genetic diversity in CR and lower in Cytb, compared to the reference population. Demographic changes and increased mutation rates may explain these findings. We show that developmental patterns and genetic composition of wild populations of a small mammal can be affected by chronic heavy metal exposure within a relatively short time. Anthropogenic stress may thus influence the evolutionary path of natural populations, with largely unpredictable ecological costs.

Skin mites in mice (Mus musculus): high prevalence of Myobia sp. (Acari, Arachnida) in Robertsonian mice.

Myobia sp. and Demodex sp. are two skin mites that infest mice, particularly immunodeficient or transgenic lab mice. In the present study, wild house mice from five localities from the Barcelona Roberstonian system were analysed in order to detect skin mites and compare their prevalence between standard (2n = 40) and Robertsonian mice (2n > 40). We found and identified skin mites through real-time qPCR by comparing sequences from the mitochondrial 16S rRNA and the nuclear 18S rRNA genes since no sequences are available so far using the mitochondrial gene. Fourteen positive samples were identified as Myobia musculi except for a deletion of 296 bp out to 465 bp sequenced, and one sample was identified as Demodex canis. Sampling one body site, the mite prevalence in standard and Robertsonian mice was 0 and 26%, respectively. The malfunction of the immune system elicits an overgrowth of skin mites and consequently leads to diseases such as canine demodicosis in dogs or rosacea in humans. In immunosuppressed mice, the probability of developing demodicosis is higher than in healthy mice. Since six murine toll-like receptors (TLRs) are located in four chromosomes affected by Robertsonian fusions, we cannot dismiss that differences in mite prevalence could be the consequence of the interruption of TLR function. Although ecological and/or morphological factors cannot be disregarded to explain differences in mite prevalence, the detection of translocation breakpoints in TLR genes or the analysis of TLR gene expression are needed to elucidate how Robertsonian fusions affect the immune system in mice.

R2d2 Drives Selfish Sweeps in the House Mouse.

A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether "selfish" genes are capable of fixation-thereby leaving signatures identical to classical selective sweeps-despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes nonrandom segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2(HC)) in natural populations. We replicate this finding in multiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2(HC) rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2(HC) is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution.

Impact of the number of Robertsonian chromosomes on germ cell death in wild male house mice.

Previous studies in the house mouse have shown that the presence of Robertsonian (Rb) metacentric chromosomes in heterozygous condition affects the process of spermatogenesis. This detrimental effect mainly depends on the number of metacentrics involved and the complexity of the resulting meiotic figures. In this study, we aimed at elucidating the relationship between the chromosomal composition and spermatogenesis impairment in mice present in an area of chromosomal polymorphism (the so-called Barcelona system BRbS) in which Rb mice are surrounded by all acrocentric animals, no established metacentric races are present and the level of structural heterozygosity is relatively low. Using the terminal deoxinucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay, we report higher frequency of apoptotic spermatogenetic cells in mice carrying six pairs of metacentrics at the homozygous state than in those carrying two or three fusions at the heterozygous state. Specifically, we detected a higher frequency of TUNEL-positive (T+) tubules and of T+ cells per tubule cross section and also a lower spermatid/spermatocyte ratio. These results indicate that the number of metacentrics at the homozygous state is more influential in determining apoptotic germ cell death than that of moderate chromosome heterozygosity. The percentage of germ cell death lower than 50 % found in our samples and the geographic distribution of the set of metacentrics within the BRbS indicate that although the spermatogenic alterations detected in this area could act as a partial barrier to gene flow, they are not sufficient to prevent Rb chromosomes from spreading in nature.

Ontogeny of the male femur: Geometric morphometric analysis applied to a contemporary Spanish population.

OBJECTIVE: To describe the morphological changes of the male femur during the adolescent growth spurt and to compare the pattern obtained with that reported previously for females. MATERIAL AND METHODS: Two hundred and forty males from a Spanish population aged between 9 and 16 years were analysed, based on telemetries. Size and shape variation of the femur was quantified by 22 2D-landmarks and analysed using geometric morphometric methods. Likewise, the variation of neck-shaft and bicondylar angles were also determined and evaluated by Student's t-test. Sexual differences were analysed by comparing results here obtained on boys with those corresponding to girls reported in a previous study. RESULTS: In males, both size and shape varied significantly with age, with males having larger dimensions than females. In general terms, these changes are generally characterised by an increase in robustness of the femur and shape modifications in the epiphyses. During growth, the neck-shaft angle decreases and the size of the greater and lesser trochanters increase. A significant increase of distal epiphyseal dimensions was recorded, mainly in the medial condyle. The angular remodeling of both the neck and the bicondylar regions of the male femur continues until 16 and 15 years, respectively. Female and male femur each followed divergent growth trajectories. Males showed a greater variability in neck-shaft and bicondylar angles than females. DISCUSSION: The timing, morphology and growth trajectories provided on the femur during development can be very helpful in anthropological, paleoanthropological and evolution studies.

Genetic recombination variation in wild Robertsonian mice: on the role of chromosomal fusions and Prdm9 allelic background.

Despite the existence of formal models to explain how chromosomal rearrangements can be fixed in a population in the presence of gene flow, few empirical data are available regarding the mechanisms by which genome shuffling contributes to speciation, especially in mammals. In order to shed light on this intriguing evolutionary process, here we present a detailed empirical study that shows how Robertsonian (Rb) fusions alter the chromosomal distribution of recombination events during the formation of the germline in a Rb system of the western house mouse (Mus musculus domesticus). Our results indicate that both the total number of meiotic crossovers and the chromosomal distribution of recombination events are reduced in mice with Rb fusions and that this can be related to alterations in epigenetic signatures for heterochromatinization. Furthermore, we detected novel house mouse Prdm9 allelic variants in the Rb system. Remarkably, mean recombination rates were positively correlated with a decrease in the number of ZnF domains in the Prdm9 gene. The suggestion that recombination can be modulated by both chromosomal reorganizations and genetic determinants that control the formation of double-stranded breaks during meiosis opens new avenues for understanding the role of recombination in chromosomal speciation.

Ontogeny of the female femur: geometric morphometric analysis applied on current living individuals of a Spanish population.

In this study we describe the development of the female femur based on the analysis of high-resolution radiographic images by means of geometric morphometrics, while assessing the usefulness of this method in these kinds of studies. The material analysed consisted of digital images in DICOM format (telemetries), corresponding to 184 left femora in anterior view, obtained from the database of the Hospital Sant Joan de Déu of Barcelona (Spain). Bones analysed corresponded to individuals from 9 to 14 years old. Size and shape variation of the entire femur was quantified by 22 two-dimensional landmarks. Landmark digitisation errors were assessed using Procrustes anova test. Centroid size (CS) variation with age was evaluated by an anova test. Shape variation was assessed by principal component analysis. A mancova test between the first five principal components and age, using the CS as covariable, was applied. Results indicated that both size and shape vary significantly with age. Several age-related shape changes remained significant after removing the allometric effect. In general, an increase in the robustness of the bone and noticeable phenotypic changes in certain areas of the femur were observed. During growth in the proximal region of the femur, the collo-diaphyseal angle decreases, the neck of the femur widens and the fovea moves to a lower position, standing more in line with the plane of the neck. Likewise, the size of the greater and lesser trochanters increase. In the distal region, a significant increase of epiphyseal dimensions was recorded, mainly in the medial condyle. The angular remodelling of the neck and the bicondylar region of the femur in females continues until 13 years old. The information provided in the present study increases our knowledge on the timing and morphology of the femur during development, and in particular the morphology of the different femoral ossification centres during development.

Variational modularity at the cell level: insights from the sperm head of the house mouse.

BACKGROUND: Modularity is an important feature in the evolvability of organisms, since it allows the occurrence of complex adaptations at every single level of biological systems. While at the cellular level the modular organization of molecular interactions has been analyzed in detail, the phenotypic modularity (or variational modularity) of cell shape remains unexplored. The mammalian spermatozoon constitutes one of the most complex and specialized cell types found in organisms. The structural heterogeneity found in the sperm head suggests an association between its inner composition, shape and specificity of function. However, little is known about the extent of the connections between these features. Taking advantage of the house mouse sperm morphology, we analyzed the variational modularity of the sperm head by testing several hypotheses related to its structural and functional organization. Because chromosomal rearrangements can affect the genotype-phenotype map of individuals and thus modify the patterns of covariation between traits, we also evaluate the effect of Robertsonian translocations on the modularity pattern of the sperm head. RESULTS: The results indicated that the house mouse sperm head is divided into three variational modules (the acrosomal, post-acrosomal and ventral spur module), which correspond to the main regions of the cytoskeletal mesh beneath the plasma membrane, i.e., the perinuclear theca. Most of the covariation is concentrated between the ventral spur and the acrosomal and post-acrosomal modules. Although the Rb fusions did not alter the main modularity pattern, they did affect the percentages of covariation between pairs of modules. CONCLUSIONS: The structural heterogeneity of the cytoskeleton is responsible for the modular organization of the sperm head shape, corroborating the role that this structure has in maintaining the cell shape. The reduction in percentages of shape covariation between pairs of modules in Rb sperms suggests that chromosomal rearrangements could induce changes in the genotype-phenotype map. Nevertheless, how these variations affect sperm fertilization success is yet to be elucidated.

Postnatal histomorphogenesis of the mandible in the house mouse.

The mandible of the house mouse, Mus musculus, is a model structure for the study of the development and evolution of complex morphological systems. This research describes the histomorphogenesis of the house mouse mandible and analyses its biological significance from the first to the eighth postnatal weeks. Histological data allowed us to test a hypothesis concerning modularity in this structure. We measured the bone growth rates by fluorescent labelling and identified the bone tissue types through microscopic analysis of histological cross-sections of the mandible during its postnatal development. The results provide evidence for a modular structure of the mouse mandible, as the alveolar region and the ascending ramus show histological differences throughout ontogeny. The alveolar region increases in length during the first two postnatal weeks by bone growth in the posterior region, while horizontally positioned incisors preclude bone growth in the anterior region. In the fourth postnatal week, growth dynamics shows a critical change. The alveolar region drifts laterally and the ramus becomes more vertical due to the medial growth direction of the coronoid region and the lateral growth of the ventral region of the ramus. Diet changes after weaning are probably involved in these morphological changes. In this way, the development of the masticatory muscles that insert on the ascending ramus may be particularly related to this shape modeling of the house mouse mandible.

Postnatal ontogeny of the femur in fossorial and semiaquatic water voles in the 3D-shape space.

Water voles of the genus Arvicola constitute an excellent subject to investigate to which extent function affects postnatal developmental growth of limb structures in phylogenetically close species. We performed a comparative analysis of postweaning femur form changes between Arvicola sapidus (semiaquatic) and Arvicola scherman (fossorial) using three-dimensional landmark-based geometric morphometrics. In both species, we observed greater femur robustness in juvenile individuals than in adult ones, probably due to the accommodation of high loads on the bone during initial locomotor efforts. Significant interspecific differences were also found in the femur size and shape of adult specimens, as well as in the postnatal allometric and phenotypic trajectories. In terms of phenotypic variation, fossorial water voles show relatively wider third and lesser trochanters, and greater femur robustness than A. sapidus, characters associated to the digging activity. In contrast, A. sapidus displays a slight increase of the greater trochanter in comparison with A. scherman, which is seemingly an adaptive response for enhancing propulsion through the water. Results evidence that certain morphological traits and differences between A. sapidus and A. scherman in the allometric and phenotypic trajectories of the femur are associated with their different locomotor mode.

A Bocage Landscape Restricts the Gene Flow of Pest Vole Populations.

The population dynamics of most animal species inhabiting agro-ecosystems may be determined by landscape characteristics, with agricultural intensification and the reduction of natural habitats influencing dispersal and hence limiting gene flow. Increasing landscape complexity would thus benefit many endangered species by providing different ecological niches, but it could also lead to undesired effects in species that can act as crop pests and disease reservoirs. We tested the hypothesis that a highly variegated landscape influences patterns of genetic structure in agricultural pest voles. Ten populations of fossorial water vole, Arvicola scherman, located in a bocage landscape in Atlantic NW Spain were studied using DNA microsatellite markers and a graph-based model. The results showed a strong isolation-by-distance pattern with a significant genetic correlation at smaller geographic scales, while genetic differentiation at larger geographic scales indicated a hierarchical pattern of up to eight genetic clusters. A metapopulation-type structure was observed, immersed in a landscape with a low proportion of suitable habitats. Matrix scale rather than matrix heterogeneity per se may have an important effect upon gene flow, acting as a demographic sink. The identification of sub-populations, considered to be independent management units, allows the establishment of feasible population control efforts in this area. These insights support the use of agro-ecological tools aimed at recreating enclosed field systems when planning integrated managements for controlling patch-dependent species such as grassland voles.

Divergence time estimation using ddRAD data and an isolation-with-migration model applied to water vole populations of Arvicola.

Molecular dating methods of population splits are crucial in evolutionary biology, but they present important difficulties due to the complexity of the genealogical relationships of genes and past migrations between populations. Using the double digest restriction-site associated DNA (ddRAD) technique and an isolation-with-migration (IM) model, we studied the evolutionary history of water vole populations of the genus Arvicola, a group of complex evolution with fossorial and semi-aquatic ecotypes. To do this, we first estimated mutation rates of ddRAD loci using a phylogenetic approach. An IM model was then used to estimate split times and other relevant demographic parameters. A set of 300 ddRAD loci that included 85 calibrated loci resulted in good mixing and model convergence. The results showed that the two populations of A. scherman present in the Iberian Peninsula split 34 thousand years ago, during the last glaciation. In addition, the much greater divergence from its sister species, A. amphibius, may help to clarify the controversial taxonomy of the genus. We conclude that this approach, based on ddRAD data and an IM model, is highly useful for analyzing the origin of populations and species.

Ecological Analysis of the Helminth Community of Microtus lusitanicus (Gerbe, 1879) (Rodentia) in Asturias (NW Spain).

The Lusitanian pine vole, Microtus lusitanicus, an endemic fossorial rodent of the Iberian Peninsula, has a burrowing behaviour and prefers to live underground. It feeds on bark and roots causing severe damage to trees. In Asturias (NW Spain), where M. lusitanicus is considered a pest in several orchards, a faunistic-ecological study was carried out to describe the helminth community of this species and the main factors that could influence its helminth component species. For this purpose, our own collection of 710 voles from several orchards of various locations in Asturias was used. Eight helminth species, four cestodes and four nematodes, were found. Statistical non-parametric tests were used to analyse the effects of extrinsic and intrinsic factors on the diversity of the helminth community and species prevalence and abundance. The results show the influence of climate variables, the year and season of capture, as well as host age, on the diversity of the helminth community and the infection parameters of some helminth species, underlining the importance of their life cycles. In addition to shedding light on the helminth community of this rodent in Asturias, the results obtained could be used to improve the biological methods applied to fight the M. lusitanicus pest.

The impact of chromosomal fusions on 3D genome folding and recombination in the germ line.

The spatial folding of chromosomes inside the nucleus has regulatory effects on gene expression, yet the impact of genome reshuffling on this organization remains unclear. Here, we take advantage of chromosome conformation capture in combination with single-nucleotide polymorphism (SNP) genotyping and analysis of crossover events to study how the higher-order chromatin organization and recombination landscapes are affected by chromosomal fusions in the mammalian germ line. We demonstrate that chromosomal fusions alter the nuclear architecture during meiosis, including an increased rate of heterologous interactions in primary spermatocytes, and alterations in both chromosome synapsis and axis length. These disturbances in topology were associated with changes in genomic landscapes of recombination, resulting in detectable genomic footprints. Overall, we show that chromosomal fusions impact the dynamic genome topology of germ cells in two ways: (i) altering chromosomal nuclear occupancy and synapsis, and (ii) reshaping landscapes of recombination.

Spermatogenesis in house mouse in a Robertsonian polymorphism zone.

Robertsonian (Rb) translocations can be important in speciation as a mechanism of postzygotic isolation between populations. Meiotic non-disjunction, gametogenic impairment, and association of impaired autosomal segments with sex chromosomes have been postulated as mechanisms responsible for reducing fertility in Rb mice. Quantitative histological studies needed to understand the role of Rb fusions in gametogenic impairment are scarce. Most research on Rb mice has analyzed meiotic non-disjunction of laboratory and wild-derived strains, which have complex or simple structural heterozygosity with large numbers of fusions. Using histological multilevel sampling, we examined spermatogenesis in mice from the Rb polymorphism area of Barcelona. We studied four chromosomal groups having: a) one Rb heterozygote fusion and 2n=39, b) one Rb heterozygote fusion and 2n=31, c) three Rb heterozygote fusions without monobrachial homology and with diploid number ranging from 2n=29 to 2n=37, and d) only Rb homozygote fusions with diploid number ranging from 2n=28 to 2n=30. Standard mice from the area surrounding the Rb zone were used as control. We analyzed morphological variables of the testes, relative frequency of stages in the seminiferous epithelium cycle, the 'round spermatids:primary spermatocytes' ratio, and other derived parameters. Our results reveal that structural homozygote mice and simple heterozygote mice having as few as one to three Rb fusions undergo greater germ cell death (GCD) than standard mice, suggesting that Rb fusions are related to increased GCD (in both the heterozygous and homozygous state) and may be the main cause of decreased gene flow between mice populations from this area.

Three-dimensional geometric morphometric analysis of the humerus: Comparative postweaning ontogeny between fossorial and semiaquatic water voles (Arvicola).

Different types of locomotion in phylogenetically close rodent species can lead to significantly different growth patterns of certain skeletal structures. In the present study, we compared the allometric and phenotypic trajectories of the humerus in semiaquatic (Arvicola sapidus) and fossorial (Arvicola scherman) water vole taxa, using three-dimensional geometric morphometrics, to investigate the relationships between functional and ontogenetic differences. Results revealed shared humerus traits between A. sapidus and A. scherman, specifically an expansion of the epicondylar and deltopectoral crests along postnatal ontogeny. In both species, the humerus of young specimens is more robust than in adults, possibly as a compensatory response for lower bone stiffness. However, significant interspecific differences were detected in all components of allometric and phenotypic trajectories. Noticeably divergent allometric trajectories were observed, probably as a result of different functional pressures exerted on this bone. Important differences in the form of the adult humerus between taxa were also found, particularly in features located in muscle insertion zones. Furthermore, the allometric regression revealed certain shape variation not associated with size in A. scherman, suggesting mechanical stress produced by the persistent digging activity during adulthood. A. scherman is a chisel-tooth digger that shares several traits in the humerus morphology with scratch-digger rodent species. Nevertheless, these shared characteristics are less pronounced in fossorial water voles, which is congruent with the different implications of the forelimb in the digging activity in these two types of diggers.

Multimethod Approach to the Early Postnatal Growth of the Mandible in Mice from a Zone of Robertsonian Polymorphism.

The western European house mouse (Mus musculus domesticus) shows high karyotypic diversity owing to Robertsonian translocations. Morphometric studies conducted with adult mice suggest that karyotype evolution due to these chromosomal reorganizations entails variation in the form and the patterns of morphological covariation of the mandible. However, information is much scarcer regarding the effect of these rearrangements on the growth pattern of the mouse mandible over early postnatal ontogeny. Here we compare mandible growth from the second to the eighth week of postnatal life between two ontogenetic series of mice from wild populations, with the standard karyotype and with Robertsonian translocations respectively, reared under the same conditions. A multi-method approach is used, including bone histology analyses of mandible surfaces and cross-sections, as well as geometric morphometric analyses of mandible form. The mandibles of both standard and Robertsonian mice display growth acceleration around weaning, anteroposterior direction of bone maturation, a predominance of bone deposition fields over ontogeny, and relatively greater expansion of the posterior mandible region correlated with the ontogenetic increase in mandible size. Nevertheless, differences exist between the two mouse groups regarding the timing of histological maturation of the mandible, the localization of certain bone remodeling fields, the temporospatial patterns of morphological variation, and the organization into two main modules. The dissimilarities in the process of mandible growth between the two groups of mice become more evident around sexual maturity, and could arise from alterations that Robertsonian translocations may exert on genes involved in the bone remodeling mechanism. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc.

Comparative postnatal histomorphogenesis of the mandible in wild and laboratory mice.

The coordinated activity of bone cells (i.e., osteoblasts and osteoclasts) during ontogeny underlies observed changes in bone growth rates (recorded in bone histology and bone microstructure) and bone remodeling patterns explaining the ontogenetic variation in bone size and shape. Histological cross-sections of the mandible in the C57BL/6J inbred mouse strain were recently examined in order to analyze the bone microstructure, as well as the directions and rates of bone growth according to the patterns of fluorescent labeling, with the aim of description of the early postnatal histomorphogenesis of this skeletal structure. Here we use the same approach to characterize the histomorphogenesis of the mandible in wild specimens of Mus musculus domesticus, from the second to the eighth week of postnatal life, for the first time. In addition, we assess the degree of similarity in this biological process between the wild specimens examined and the C57BL/6J laboratory strain. Bone microstructure data show that M. musculus domesticus and the C57BL/6J strain differ in the temporospatial pattern of histological maturation of the mandible, which particularly precludes the support of mandibular organization into the alveolar region and the ascending ramus modules at the histological level in M. musculus domesticus. The patterns of fluorescent labeling reveal that the mandible of the wild mice exhibits temporospatial differences in the remodeling pattern, as well as higher growth rates particularly after weaning, compared to the laboratory mice. Since the two mouse groups were reared under the same conditions, the dissimilarities found suggest the existence of differences between the groups in the genetic regulation of bone remodeling, probably as a result of their different genetic backgrounds. Despite the usual suitability of inbred mouse strains as model organisms, inferences from them to natural populations regarding bone growth should be made with caution.