Lines of least resistance and genetic architecture of house mouse (Mus musculus) mandible shape.

Evolution along "lines of least resistance (LLR)" is a well-established phenomenon, which is ultimately based on variational properties of the developmental system. However, it has remained unclear which aspects of development are responsible for observed distributions of variation. This article suggests that house mouse mandible shape may present an opportunity for future research in this field. The genetic architecture of mouse mandible shape has been investigated in the laboratory, and its evolution has been surveyed in studies on natural variation. Here, I ask whether evolutionary diversification of mandible shape follows "LLR" by comparing principal directions of genetic and evolutionary variation, and I assess the potential contribution of specific genomic regions to evolutionary divergence along these directions. The role of two aspects of development, QTL number (presumably reflecting mutational target size) and canalization, is comparatively assessed. Overall, our results demonstrate a strong tendency of genetic and evolutionary systems to vary along similar directions, suggesting that mandible shape evolves along LLR at the level of populations, subspecies and species. At the level of genetic factors, effects bearing similarity to directions of evolution are significantly overrepresented, providing support for the mutational target size hypothesis. A role for canalization is not supported by a clear correlation between directions of evolution and size of genetic effects; however, the evidence for canalization remains ambiguous. These results provide some insights into how the developmental system may shape the variational properties of genetic systems and thus influence the direction of evolution.

Exploring the effects of gene dosage on mandible shape in mice as a model for studying the genetic basis of natural variation.

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.

Micro-evolutionary divergence patterns of mandible shapes in wild house mouse (Mus musculus) populations.

BACKGROUND: Insights into the micro-evolutionary patterns of morphological traits require an assessment of the natural variation of the trait within and between populations and closely related species. The mouse mandible is a particularly suitable morphological trait for such an analysis, since it has long been used as a model to study the quantitative genetics of shape. In addition, many distinct populations, sub-species and closely related species are known for the house mouse. However, morphological comparisons among wild caught animals require an assessment in how far environmental and technical factors could interfere with the shape change measurements. RESULTS: Using geometric morphometrics, we have surveyed mandible shapes in 15 natural populations of the genus Mus, with a focus on the subspecies Mus musculus domesticus. In parallel we have carefully assessed possibly confounding technical and biological factors. We find that there are distinct differences on average between populations, subspecies and species, but these differences are smaller than differences between individuals within populations. Populations from summer-dry regions, although more ancestral, are less distinct from each other than are populations from the more recently colonized northern areas. Populations with especially distinct shapes occur in an area of sympatry of M. m. domesticus and M. spretus and on recently colonized sub-antarctic islands. We have also studied a number of inbred strains to assess in how far their mandible shapes resemble those from the wild. We find that they fall indeed into the shape space of natural variation between individuals in populations. CONCLUSIONS: Although mandible shapes in natural populations can be influenced by environmental variables, these influences are insufficient to explain the average extent of shape differences between populations, such that evolutionary processes must be invoked to explain this level of diversity. We discuss that adaptive evolution may contribute to shape changes between populations, in particular in newly colonized areas. A comparison between inbred strains and wild mice suggests that the laboratory environment has no major systematic effect on the mandible shape and that such strains can be used as representatives of the natural shape differences between individuals.

A comparative assessment of mandible shape in a consomic strain panel of the house mouse (Mus musculus)--implications for epistasis and evolvability of quantitative traits.

BACKGROUND: Expectations of repeatedly finding associations between given genes and phenotypes have been borne out by studies of parallel evolution, especially for traits involving absence or presence of characters. However, it has rarely been asked whether the genetic basis of quantitative trait variation is conserved at the intra- or even at the interspecific level. This question is especially relevant for shape, where the high dimensionality of variation seems to require a highly complex genetic architecture involving many genes. RESULTS: We analyse here the genetic effects of chromosome substitution strains carrying M. m. musculus chromosomes in a largely M. m. domesticus background on mandible shape and compare them to the results of previously published QTL mapping data between M. m. domesticus strains. We find that the distribution of genetic effects and effect sizes across the genome is consistent between the studies, while the specific shape changes associated with the chromosomes are different. We find also that the sum of the effects from the different M. m. musculus chromosomes is very different from the shape of the strain from which they were derived, as well as all known wild type shapes. CONCLUSIONS: Our results suggest that the relative chromosome-wide effect sizes are comparable between the long separated subspecies M. m. domesticus and M. m. musculus, hinting at a relative stability of genes involved in this complex trait. However, the absolute effect sizes and the effect directions may be allele-dependent, or are context dependent, i.e. epistatic interactions appear to play an important role in controlling shape.

EST based phylogenomics of Syndermata questions monophyly of Eurotatoria.

BACKGROUND: The metazoan taxon Syndermata comprising Rotifera (in the classical sense of Monogononta+Bdelloidea+Seisonidea) and Acanthocephala has raised several hypotheses connected to the phylogeny of these animal groups and the included subtaxa. While the monophyletic origin of Syndermata and Acanthocephala is well established based on morphological and molecular data, the phylogenetic position of Syndermata within Spiralia, the monophyletic origin of Monogononta, Bdelloidea, and Seisonidea and the acanthocephalan sister group are still a matter of debate. The comparison of the alternative hypotheses suggests that testing the phylogenetic validity of Eurotatoria (Monogononta+Bdelloidea) is the key to unravel the phylogenetic relations within Syndermata. The syndermatan phylogeny in turn is a prerequisite for reconstructing the evolution of the acanthocephalan endoparasitism. RESULTS: Here we present our results from a phylogenomic approach studying i) the phylogenetic position of Syndermata within Spiralia, ii) the monophyletic origin of monogononts and bdelloids and iii) the phylogenetic relations of the latter two taxa to acanthocephalans. For this analysis we have generated EST libraries of Pomphorhynchus laevis, Echinorhynchus truttae (Acanthocephala) and Brachionus plicatilis (Monogononta). By extending these data with database entries of B. plicatilis, Philodina roseola (Bdelloidea) and 25 additional metazoan species, we conducted phylogenetic reconstructions based on 79 ribosomal proteins using maximum likelihood and bayesian approaches. Our findings suggest that the phylogenetic position of Syndermata within Spiralia is close to Platyhelminthes, that Eurotatoria are not monophyletic and that bdelloids are more closely related to acanthocephalans than monogononts. CONCLUSION: Mapping morphological character evolution onto molecular phylogeny suggests the (partial or complete) reduction of the corona and the emergence of a retractable anterior end (rostrum, proboscis) before the separation of Acanthocephala. In particular, the evolution of a rostrum might have been a key event leading to the later evolution of the acanthocephalan endoparasitism, given the enormous relevance of the proboscis for anchoring of the adults to the definitive hosts' intestinal wall.

Whole-mount in situ hybridization in the rotifer Brachionus plicatilis representing a basal branch of lophotrochozoans.

In order to broaden the comparative scope of evolutionary developmental biology and to refine our picture of animal macroevolution, it is necessary to establish new model organisms, especially from previously underrepresented groups, like the Lophotrochozoa. We have established the culture and protocols for molecular developmental biology in the rotifer species Brachionus plicatilis Müller (Rotifera, Monogononta). Rotifers are nonsegmented animals with enigmatic basal position within the lophotrochozoans and marked by several evolutionary novelties like the wheel organ (corona), the median eye, and the nonpaired posterior foot. The expression of Bp-Pax-6 is shown using whole-mount in situ hybridization. The inexpensive easy culture and experimental tractability of Brachionus as well as the range of interesting questions to which it holds the key make it a promising addition to the "zoo" of evo-devo model organisms.