[Show abstract][Hide abstract] ABSTRACT: The phylogeography of the house mouse (Mus musculus L.), an emblematic species for genetic and biomedical studies, is only partly understood, essentially because of a sampling bias towards its most peripheral populations in Europe, Asia and the Americas. Moreover, the present-day phylogeographic hypotheses stem mostly from the study of mitochondrial lineages. In this article, we complement the mtDNA studies with a comprehensive survey of nuclear markers (19 microsatellite loci) typed in 963 individuals from 47 population samples, with an emphasis on the putative Middle-Eastern centre of dispersal of the species.
Based on correspondence analysis, distance and allele-sharing trees, we find a good coherence between geographical origin and genetic make-up of the populations. We thus confirm the clear distinction of the three best described peripheral subspecies, M. m. musculus, M. m. domesticus and M. m. castaneus. A large diversity was found in the Iranian populations, which have had an unclear taxonomic status to date. In addition to samples with clear affiliation to M. m. musculus and M. m. domesticus, we find two genetic groups in Central and South East Iran, which are as distinct from each other as they are from the south-east Asian M. m. castaneus. These groups were previously also found to harbor distinct mitochondrial haplotypes.
We propose that the Iranian plateau is home to two more taxonomic units displaying complex primary and secondary relationships with their long recognized neighbours. This central region emerges as the area with the highest known diversity of mouse lineages within a restricted geographical area, designating it as the focal place to study the mechanisms of speciation and diversification of this species.
[Show abstract][Hide abstract] ABSTRACT: Populations and subspecies of the house mouse Mus musculus were able to invade new regions worldwide in the wake of human expansion. Here we investigate the origin and colonization history of the house mouse inhabiting the small island of Heligoland on the German Bight - Mus musculus helgolandicus. It was first described by Zimmermann in 1953, based on morphological descriptions which were considered to be a mosaic between the subspecies M. m. domesticus and M. m. musculus. Since mice on islands are excellent evolutionary model systems, we have focused here on a molecular characterization and an extended phenotype analysis.
The molecular data show that the mice from Heligoland are derived from M. m. domesticus based on mitochondrial D-loop sequences as well as on four nuclear diagnostic markers, including one each from the sex-chromosomes. STRUCTURE analysis based on 21 microsatellite markers assigns Heligoland mice to a distinct population and D-loop network analysis suggests that they are derived from a single colonization event. In spite of mice from the mainland arriving by ships, they are apparently genetically refractory against further immigration. Mutation frequencies in complete mitochondrial genome sequences date the colonization age to approximately 400 years ago. Complete genome sequences from three animals revealed a genomic admixture with M. m. musculus genomic regions with at least 6.5 % of the genome affected. Geometric morphometric analysis of mandible shapes including skull samples from two time points during the last century suggest specific adaptations to a more carnivorous diet.
The molecular and morphological analyses confirm that M. m. helgolandicus consists of a distinct evolutionary lineage with specific adaptations. It shows a remarkable resilience against genetic mixture with mainland populations of M. m. domesticus despite major disturbances in the past century and a high ship traffic. The genomic admixture with M. m. musculus genetic material may have contributed to the genomic distinction of the Heligoland mice. In spite of its young age, M. m. helgolandicus may thus be considered as a true subspecies of Mus, whose evolution was triggered through fast divergence on a small island.
[Show abstract][Hide abstract] ABSTRACT: Poleward range expansions are commonly attributed to global change, but could alternatively be driven by rapid evolutionary adaptation. A well-documented example of a range expansion during the past decades is provided by the European wasp spider Argiope bruennichi. Using ecological niche modeling, thermal tolerance experiments and a genome-wide analysis of gene expression divergence, we show that invasive populations have adapted to novel climatic conditions in the course of their expansion. Their climatic niche shift is mirrored in an increased cold tolerance and a population-specific and functionally differentiated gene expression response. We generated an Argiope reference genome sequence and used population genome re-sequencing to assess genomic changes associated with the new climatic adaptations. We find clear genetic differentiation and a significant admixture with alleles from East Asian populations in the invasive Northern European populations. Population genetic modeling suggests that at least some of these introgressing alleles have contributed to the new adaptations during the expansion. Our results thus confirm the notion that range expansions are not a simple consequence of climate change, but are accompanied by fast genetic changes and adaptations that may be fuelled through admixture between long separated lineages. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Global Change Biology 07/2015; DOI:10.1111/gcb.13042 · 8.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The identification of the genes involved in morphological variation in nature is still a major challenge. Here we explore a new approach: we combine 178 samples from a natural hybrid zone between two subspecies of the house mouse (Mus musculus domesticus and Mus musculus musculus), and high coverage of the genome (~145K SNPs) to identify loci underlying craniofacial shape variation. Due to the long history of recombination in the hybrid zone, high mapping resolution is anticipated. The combination of genomes from subspecies allows the mapping of both, variation within subspecies and intersubspecific differences, thereby increasing the overall amount of causal genetic variation than can be detected. Skull and mandible shape were measured using 3D landmarks and geometric morphometrics. Using principle component axes as phenotypes, and a linear mixed model accounting for genetic relatedness in the mapping populations, we identified 9 genomic regions associated with skull and 10 with mandible shape. High mapping resolution (median size of significant regions = 148 kb) enabled identification of single or few candidate genes in most cases. Some of the genes act as regulators or modifiers of signaling pathways relevant for morphological development and bone formation, including several with known craniofacial phenotypes in mice and humans. The significant associations combined explain 13% and 7% of the skull and mandible shape variation. In addition, a positive correlation was found between chromosomal length and proportion of variation explained. Our results suggest a complex genetic architecture for shape traits, and support a polygenic model.This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Parentally biased expression of transcripts (genomic imprinting) in adult tissues, including the brain, can influence and possibly drive the evolution of behavioral traits. We have previously found that paternally determined cues are involved in population-specific mate choice decisions between two populations of the Western house mouse (M. m. domesticus). Here we ask whether this could be mediated by genomically imprinted transcripts that are subject to fast differentiation between these populations. We focus on three organs that are of special relevance for mate choice and behavior: the vomeronasal organ (VNO), the hypothalamus, and the liver. To first identify candidate transcripts at a genome-wide scale, we used reciprocal crosses between M. m. domesticus and M. m. musculus inbred strains and RNA sequencing of the respective tissues. Using a false discovery cutoff derived from mock reciprocal cross comparisons, we find a total of 66 imprinted transcripts, 13 of which have previously not been described as imprinted. The largest number of imprinted transcripts were found in the hypothalamus; fewer were found in the VNO, and the least were found in the liver. To assess molecular differentiation and imprinting in the wild-derived M. m. domesticus populations, we sequenced the RNA of the hypothalamus from individuals of these populations. This confirmed the presence of the above identified transcripts also in wild populations and allowed us to search for those that show a high genetic differentiation between these populations. Our results identify the Ube3a - Snrpn imprinted region on chromosome 7 as a region that encompasses the largest number of previously not described transcripts with paternal expression bias, several of which are at the same time highly differentiated. For four of these, we confirmed their imprinting status via SNP-specific pyro-sequencing assays with RNA from reciprocal crosses. In addition, we find the paternally expressed Peg13 transcript within the Trappc9 gene region on chromosome 15 to be highly differentiated. Interestingly, both regions have been implicated in Prader-Willi nervous system disorders in humans. We suggest that these genomically imprinted regions are candidates for influencing the population-specific mate-choice in mice.
[Show abstract][Hide abstract] ABSTRACT: Background - In previous work, the authors described a software package for the digitisation of 3D landmarks for use in geometric morphometrics. In this paper, we describe extensions to this software that allow semi-automatic localisation of 3D landmarks, given a database of manually annotated training images. Multi-stage registration was applied to align image patches from the database to a query image, and the results from multiple database images were combined using an array-based voting scheme. The software automatically highlights points that have been located with low confidence, allowing manual correction.
Results - Evaluation was performed on micro-CT images of rodent skulls for which two independent sets of manual landmark annotations had been performed. This allowed assessment of landmark accuracy in terms of both the distance between manual and automatic annotations, and the repeatability of manual and automatic annotation. Automatic annotation attained accuracies equivalent to those achievable through manual annotation by an expert for 87.5% of the points, with significantly higher repeatability.
Conclusions - Whilst user input was required to produce the training data and in a final error correction stage, the software was capable of reducing the number of manual annotations required in a typical landmark identification process using 3D data by a factor of ten, potentially allowing much larger data sets to be annotated and thus increasing the statistical power of the results from subsequent processing e.g. Procrustes/principal component analysis. The software is freely available, under the GNU General Public Licence, from our web-site (www.tina-vision.net).
Frontiers in Zoology 08/2014; 11(61). DOI:10.1186/s12983-014-0061-1 · 3.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Copy–number variants (CNVs) may play an important role in early adaptations, potentially facilitating rapid divergence of populations. We describe an approach to study this question by investigating CNVs present in natural populations of mice in the early stages of divergence and their involvement in selective sweeps. We have analysed individuals from two recently diverged natural populations of the house mouse (Mus musculus domesticus) from Germany and France using custom, high–density, comparative genome hybridisation arrays (CGH) that covered almost 164Mb and 2,444 genes. 1,861 of those genes we previously identified as differentially expressed between these populations, while the expression of the remaining genes was invariant. In total, we identified 1,868 CNVs across all 10 samples, 200bp to 600kb in size and affecting 424 genic regions. Roughly two thirds of all CNVs found were deletions. We found no enrichment of CNVs among the differentially expressed genes between the populations compared to the invariant ones, nor any meaningful correlation between CNVs and gene expression changes. Among the CNV genes, we found cellular component gene ontology categories of the synapse overrepresented among all the 2,444 genes tested. To investigate potential adaptive significance of the CNV regions, we selected six that showed large differences in frequency of CNVs between the two populations and analysed variation in at least two microsatellites surrounding the loci in a sample of 46 unrelated animals from the same populations collected in field trappings. We identified two loci with large differences in microsatellite heterozygosity (Sfi1 and Glo1/Dnahc8 regions) and one locus with low variation across the populations (Cmah), thus suggesting that these genomic regions might have recently undergone selective sweeps. Interestingly, the Glo1 CNV has previously been implicated in anxiety–like behaviour in mice, suggesting a differential evolution of a behavioural trait.
Frontiers in Genetics 06/2014; 5:153. DOI:10.3389/fgene.2014.00153
[Show abstract][Hide abstract] ABSTRACT: It has long been known that rodents emit signals in the ultrasonic range, but their role in social communication and mating is still under active exploration. While inbred strains of house mice have emerged as a favourite model to study ultrasonic vocalisation (USV) patterns, studies in wild animals and natural situations are still rare. We focus here on two wild derived mouse populations. We recorded them in dyadic encounters for extended periods of time to assess possible roles of USVs and their divergence between allopatric populations. We have analysed song frequency and duration, as well as spectral features of songs and syllables. We show that the populations have indeed diverged in several of these aspects and that USV patterns emitted in a mating context differ from those emitted in same sex encounters. We find that females vocalize not less, in encounters with another female even more than males. This implies that the current focus of USVs being emitted mainly by males within the mating context needs to be reconsidered. Using a statistical syntax analysis we find complex temporal sequencing patterns that could suggest that the syntax conveys meaningful information to the receivers. We conclude that wild mice use USV for complex social interactions and that USV patterns can diverge fast between populations.
PLoS ONE 05/2014; 9(5):e97244. DOI:10.1371/journal.pone.0097244 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Comparative genomics have brought much insight into the de novo emergence of genes. Two new studies in Drosophila explore the dynamics of gene gain and loss at the population and species levels, extending our view on the life cycle of genes.
Current biology: CB 03/2014; 24(6):R238-40. DOI:10.1016/j.cub.2014.02.016 · 9.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although microarrays are analysis tools in biomedical research, they are known to yield noisy output that usually requires experimental confirmation. To tackle this problem, many studies have developed rules for optimizing probe design and devised complex statistical tools to analyze the output. However, less emphasis has been placed on systematically identifying the noise component as part of the experimental procedure. One source of noise is the variance in probe binding, which can be assessed by replicating array probes. The second source is poor probe performance, which can be assessed by calibrating the array based on a dilution series of target molecules. Using model experiments for copy number variation and gene expression measurements, we investigate here a revised design for microarray experiments that addresses both of these sources of variance.
Two custom arrays were used to evaluate the revised design: one based on 25 mer probes from an Affymetrix design and the other based on 60 mer probes from an Agilent design. To assess experimental variance in probe binding, all probes were replicated ten times. To assess probe performance, the probes were calibrated using a dilution series of target molecules and the signal response was fitted to an adsorption model. We found that significant variance of the signal could be controlled by averaging across probes and removing probes that are nonresponsive or poorly responsive in the calibration experiment. Taking this into account, one can obtain a more reliable signal with the added option of obtaining absolute rather than relative measurements.
The assessment of technical variance within the experiments, combined with the calibration of probes allows to remove poorly responding probes and yields more reliable signals for the remaining ones. Once an array is properly calibrated, absolute quantification of signals becomes straight forward, alleviating the need for normalization and reference hybridizations.
PLoS ONE 03/2014; 9(3):e91295. DOI:10.1371/journal.pone.0091295 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hybrid dysfunction, a common feature of reproductive barriers between species, is often caused by negative epistasis between loci ("Dobzhansky-Muller incompatibilities"). The nature and complexity of hybrid incompatibilities remain poorly understood because identifying interacting loci that affect complex phenotypes is difficult. With subspecies in the early stages of speciation, an array of genetic tools, and detailed knowledge of reproductive biology, house mice (Mus musculus) provide a model system for dissecting hybrid incompatibilities. Male hybrids between M. musculus subspecies often show reduced fertility. Previous studies identified loci and several X chromosome-autosome interactions that contribute to sterility. To characterize the genetic basis of hybrid sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven 'hotspots,' seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL-but not cis eQTL-were substantially lower when mapping was restricted to a 'fertile' subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility. The integrated mapping approach we employed is applicable in a broad range of organisms and we advocate for widespread adoption of a network-centered approach in speciation genetics.
[Show abstract][Hide abstract] ABSTRACT: Comparing the anatomies of more than 100 different species of ants reveals that worker ants have enlarged necks, not seen in queens, that allow them to lift and carry objects many times heavier than themselves.
[Show abstract][Hide abstract] ABSTRACT: Maps generated using a modified the NR database from NCBI as reference, taxonomic relationships from NCBI Taxonomy to define the most populated branches of the phylogenetic tree for each species and blastp e-value of 1e-3
[Show abstract][Hide abstract] ABSTRACT: Mandible shape in the mouse is a complex trait that is influenced by many genetic factors. However, little is known about the action of single genes on adult mandible shape so far, since most developmentally relevant genes are already required during embryogenesis, i.e., knockouts lead to embryonic death or severe deformations, before the mandible is fully formed. We employ here a geometric morphometric approach to identify subtle phenotypic differences caused by dosage effects of candidate genes. We use mouse strains with specific gene modifications (knockouts and knockins) to compare heterozygous animals with controls from the same stock, which is expected to be equivalent to a change of gene expression of the respective locus. Such differences in expression level are also likely to occur as part of the natural variation. We focus on Bmp pathway genes (Bmp4, its antagonist Noggin, and combinations of Bmp5-7 genotypes), but include also two other developmental control genes suspected to affect mandible development in some way (Egfr and Irf6). In addition, we study the effects of Hoxd13, as well as an extracellular matrix constituent (Col2a1). We find that subtle but significant shape differences are caused by differences in gene dosage of several of these genes. The changes seen for Bmp4 and Noggin are partially compatible with the action of these genes known from birds and fish. We find significant shape changes also for Hoxd13, although this gene has so far only been implicated in skeletal patterning processes of the limbs. Comparing the effect sizes of gene dosage changes to the variation found in natural populations of mice as well as quantitative trait loci (QTL) effects on mandible shape, we find that the effect sizes caused by gene dosage changes are at the lower end of the spectrum of natural variation, but larger than the average additive effects found in QTL studies. We conclude that studying gene dosage effects have the potential to provide new insights into aspects of craniofacial development, variation, and evolution.
Development Genes and Evolution 04/2013; 223(5). DOI:10.1007/s00427-013-0443-y · 2.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
The introduction and statistical formalisation of landmark-based methods for analysing biological shape has made a major impact on comparative morphometric analyses. However, a satisfactory solution for including information from 2D/3D shapes represented by ‘semi-landmarks’ alongside well-defined landmarks into the analyses is still missing. Also, there has not been an integration of a statistical treatment of measurement error in the current approaches.
We propose a procedure based upon the description of landmarks with measurement covariance, which extends statistical linear modelling processes to semi-landmarks for further analysis. Our formulation is based upon a self consistent approach to the construction of likelihood-based parameter estimation and includes corrections for parameter bias, induced by the degrees of freedom within the linear model. The method has been implemented and tested on measurements from 2D fly wing, 2D mouse mandible and 3D mouse skull data. We use these data to explore possible advantages and disadvantages over the use of standard Procrustes/PCA analysis via a combination of Monte-Carlo studies and quantitative statistical tests. In the process we show how appropriate weighting provides not only greater stability but also more efficient use of the available landmark data. The set of new landmarks generated in our procedure (‘ghost points’) can then be used in any further downstream statistical analysis.
Our approach provides a consistent way of including different forms of landmarks into an analysis and reduces instabilities due to poorly defined points. Our results suggest that the method has the potential to be utilised for the analysis of 2D/3D data, and in particular, for the inclusion of information from surfaces represented by multiple landmark points.
Frontiers in Zoology 04/2013; 10(1):16. DOI:10.1186/1742-9994-10-16 · 3.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The evolutionary divergence of cues for mate recognition can contribute to early stages of population separation. We compare here two allopatric populations of house mice (Mus musculus domesticus) that have become separated about 3000 years ago. We have used paternity assignments in semi-natural environments to study the degree of mutual mate recognition according to population origin under conditions of free choice and overlapping generations. Our results provide insights into the divergence of mating cues, but also for the mating system of house mice. We find frequent multiple mating, occurrence of inbreeding and formation of extended family groups. In addition, many animals show strong mate fidelity, that is, frequent choice of the same mating partners in successive breeding cycles, indicating a role for familiarity in mating preference. With respect to population divergence, we find evidence for assortative mating, but only under conditions where the animals had time to familiarize themselves with mating partners from their own population. Most interestingly, the first-generation offspring born in the enclosure showed a specific mating pattern. Although matings between animals of hybrid population origin with animals of pure population origin should have occurred with equal frequency with respect to matching the paternal or maternal origin, paternal matching with mates from their own populations occurred much more often. Our findings suggest that paternally imprinted cues play a role in mate recognition between mice and that the cues evolve fast, such that animals of populations that are separated since not more than 3000 years can differentially recognize them.
[Show abstract][Hide abstract] ABSTRACT: Poleward range expansions are observed for an increasing number of species, which may be an effect of global warming during the past decades. However, it is still not clear in how far these expansions reflect simple geographical shifts of species ranges, or whether new genetic adaptations play a role as well. Here, we analyse the expansion of the wasp spider Argiope bruennichi into Northern Europe during the last century. We have used a range-wide sampling of contemporary populations and historical specimens from museums to trace the phylogeography and genetic changes associated with the range shift. Based on the analysis of mitochondrial, microsatellite and SNP markers, we observe a higher level of genetic diversity in the expanding populations, apparently due to admixture of formerly isolated lineages. Using reciprocal transplant experiments for testing overwintering tolerance, as well as temperature preference and tolerance tests in the laboratory, we find that the invading spiders have possibly shifted their temperature niche. This may be a key adaptation for survival in Northern latitudes. The museum samples allow a reconstruction of the invasion's genetic history. A first, small-scale range shift started around 1930, in parallel with the onset of global warming. A more massive invasion of Northern Europe associated with genetic admixture and morphological changes occurred in later decades. We suggest that the latter range expansion into far Northern latitudes may be a consequence of the admixture that provided the genetic material for adaptations to new environmental regimes. Hence, global warming could have facilitated the initial admixture of populations and this resulted in genetic lineages with new habitat preferences.
[Show abstract][Hide abstract] ABSTRACT: Although microarrays are routine analysis tools in biomedical research,
they still yield noisy output that often requires experimental
confirmation. Many studies have aimed at optimizing probe design and
statistical analysis to tackle this problem. However, less emphasis has
been placed on controlling the noise inherent to the experimental
approach. To address this problem, we investigate here a procedure that
controls for such experimental variance and combine it with an
assessment of probe performance. Two custom arrays were used to evaluate
the procedure: one based on 25mer probes from an Affymetrix design and
the other based on 60mer probes from an Agilent design. To assess
experimental variance, all probes were replicated ten times. To assess
probe performance, the probes were calibrated using a dilution series of
target molecules and the signal response was fitted to an absorption
model. We found that significant variance of the signal could be
controlled by averaging across probes and removing probes that are
nonresponsive. Thus, a more reliable signal could be obtained using our
procedure than conventional approaches. We suggest that once an array is
properly calibrated, absolute quantification of signals becomes straight
forward, alleviating the need for normalization and reference