Variation und Variabilität der Unterkieferform in der Hausmaus

In dieser Doktorarbeit beschreibe ich zunächst die Variation in der Unterkieferform wildgefangener Mäuse, wobei das Hauptaugenmerk auf der Hausmaus, Mus musculus, liegt. Unter Einbeziehung gefangengehaltener Mäuse, von Inzuchtstämmen und einiger Experimentalpopulationen versuche ich dann herauszuarbeiten, welche biologischen Prozesse die beobachteten Variationsmuster erklären könnten. Hierbei kommen auch genetische und entwicklungsbiologische Aspekte zum Tragen, d.h. die der Variation zugrundeliegende Variabilität. Meine wichtigsten Ergebnisse sind folgende: 1) Mahalanobis-Distanzen basierend auf canonical-variates-Analyse von Prokrustes-Koordinaten sind ein gutes Maß für den Formunterschied zwischen zwei Populationen. In Kombination mit der Benutzung mikrotomographischer Aufnahmen von Mäuse-Hemimandibeln sind sie ausreichend robust gegenüber verschiedenen Problemen betreffend Qualität der Proben und Weiterverarbeitung der Daten, als da sind Begrenzungen der Probengröße, systematische Fehler in Bezug auf Alter, Geschlecht und Größe der Tiere, Orientierung der Specimen im Tomographen, Präparation der Knochen und Registrierung der Meßpunkte. 2) Phänotypische Plastizität als Reaktion auf Umweltfaktoren beeinflußt die Unterkieferform weniger stark, als eß dem durschschnittlichen Formunterschied zwischen zwei Populationen entspricht, d.h. Formunterschiede zwischen wilden Populationen beruhen zu großen Teilen auf genetischen Unterschieden. 3) Verschiedene Kategorien von Selektion könnten auf die Unterkieferform gewirkt haben. Vier Populationen von Mäusen aus sommertrockenen Gebieten haben sehr ähnliche Formen, was bedeuten könnte, daß diese Form durch stabilisierende Selektion konserviert wurde. Eine Population von M. m. domesticus aus einem Dorf in den spanischen Pyreneen, wo die Mäuse sympatrisch mit M.spretus lebten, ist in ihrer Unterkieferform stark divergent von andern M. musculus. Es könnte sich hierbei um einen Fall von character displacement, d.h. evolutionäre Betonung der Nischenunterschiede zur Konkurenzvermeidung, handeln. Zwei Populationen von M. m. domesticus, die sich von nicht weit zurückliegenden Kolonisationsereignissen durch menschlichen Transport auf den subantarktischen Kerguelen-Inseln herleiten, weichen von anderen Hausmäusen in teilweise ähnlichen Richtungen ab, was einen Fall paralleler Anpassung an das kalte Klima auf diesen Inseln darstellen könnte. 4) Inzuchtstämme der Hausmaus unterscheiden sich stärker von wilden Hausmäusen und voneinander als unterschiedliche Arten in der Natur. Dies beruht vermutlich auf nichtadditiven, epistatischen Interaktionen zwichen and der Morphogenese beteiligten Genen. Diese Hypothese wird unterstützt durch die Beobachtung, daß F1-Tiere aus Kreuzungen zwischen verschiedenen Inzuchtstämmen nicht lediglich wie Zwischeformen zwischen den Parentalstämmen aussehen, sondern sich wieder teilweise der Wildform annähern. 5) Genetisch diverse (nicht ingezüchtete) Populationen von wilden Hausmäusen, die im Labor gehalten werden, verändern ihre Unterkieferform im Lauf weniger Generationen, wenn auch weniger stark als Inzuchtstämme. Sie unterscheiden sich auch weniger voneinander als dies bei Inzuchtstämmen der Fall ist. Möglicherweise liegt hier ein noch unbekannter (epigenetischer) Mechanismus zugrunde, der durch die Laborhaltung induziert wird. 6) Die Formabweichungen von Kerguelen-Mäusen, Inzuchtstämmen und gefangen gehaltenen Wildmäusen („abgeleitete Populationen“) sind in ihren Richtungen nicht zufallsverteilt. Dieses Muster muß aus einer merkmalsbezogenen Perspektive untersucht werden. Die geometrische Morphometrie bietet dafür keine geeigneten Methoden. Einfache Alternativmethoden, basierend auf Meßstrecken, ermöglichen es, die Ähnlichkeit der Richtungen von Formveränderungen zu quantifizieren und die beteiligten Regionen des Unterkiefers zu identifizieren. 7) Mithilfe eines eigens entwickelten manuellen Protokolls wurden 20 Gruppen miteinander kovariierender Meßstrecken (interlandmark distances, ILMDs) identifiziert, die wiederum in 5 „Hauptmerkmale“ gruppiert werden können. Diese resultieren möglicherweise aus unterschiedlicher Zuweisung von begrenzten Wachstumsressourcen zu den Fortsätzen des Unterkiefers oder aus funktioneller Koppelung zwischen voderen und hinteren Bereichen. 8) Die 5 Hauptmerkmale „erklären“ große Anteile der Variation in verschiedenen Zusammenhängen: Abweichung der „abgeleiteten Populationen“ von Wildmäusen, Variation innerhalb sowohl genetisch diverser als auch ingezüchteter Populationen (im letzteren Fall besteht ein Zusammenhang zur Instabilität von Entwicklungsvorgängen), „epistatische Abweichungen“ bei Auszuchttieren vom Mittelwert zwichen den Elternstämmen, sowie nachgeburtliche Formveränderungen. Diese Vielfalt von Zusammenhängen ist ein Hinweis darauf, daß ein Großteil genetischer und entwicklungsbiologischer Veränderungen sich in einer begrenzten Anzahl von Formveränderungen niederschlägt. Die 5 Hauptmerkmale sind allerdings von geringerer Bedeutung für die Erklärung von Formunterschieden zwischen Populationen und Arten. 9) Unter Zusammenfassung der Hinweise auf die epistatische Grundlage bestimmter Formunterschiede und der spezifischen Zusammenhänge, in denen sich diese Formunterschiede manifestieren, schlage ich folgende Hypothese vor: epistatische Varianz und Instabilität der Entwicklung produzieren einen Großteil der Variation innerhalb von Populationen. Die Unterschiede zwichen Populationen und Arten, die durch genetischer Evolution entstehen, beruhen hauptsächlich auf additiver genetischer Varianz, die andere Formunterschiede hervorbringt als Epistasias und Instabilität. Diese Varianz wird möglicherweise durch stabilisierende Selektion eingeschränkt und spielt daher innerhalb von Populationen eine geringere Rolle.In this thesis, I provide a description of the shape space of wild mouse mandibles with a focus on Mus musculus. Extending the comparisons to captive mice, inbred strains and some experimental populations, I try to infer which biological processes might account for observed patterns of shape variation, including genetic and developmental aspects (variability). I obtain the following results: 1) Mahalanobis distances based on CVA of Procrustes coordinates are a good measure of the global shape difference between two populations. Combined with the use of two-dimensional projections of µCT images of mouse hemimandibles, they are sufficiently robust in the face of diverse problems with sample quality and data processing, such as limitations in sample size, sampling errors with respect to sex, age and size of the animals, orientation of the samples inside the µCT scanner, preparation of bones and landmark digitization error. 2) Phenotypic plasticity as a reaction to environmental differences affects mandible shape by a smaller amount than the average distance between samples of wild-caught populations, suggesting that the shape differences between wild populations mostly have a genetic basis. 3) Various types of selection may have acted on shape. Four populations of mice from summer-dry regions cluster closely together, indicating that stabilizing selection may have conserved their shape. A M. m. domesticus sample from a site in Spain where the mice live in sympatry with a population of M. spretus is highly divergent from other M. musculus. This could represent a case of character displacement. Two populations of M. m. domesticus representing rather recent events of colonization on the subantarctic Kerguelen islands have diverged from other M. musculus in partially similar directions, which could represent an adaptation to the cold climate on these islands. 4) Inbred mouse strains are more divergent from wild mice and from each other than different species in nature, suggesting that nonadditive mechanisms of inheritance, especially epistasis, are important determinants of shape. This idea is supported by the finding that F1 of outcrosses between inbred strains look more similar to wild mice than their parentals, i. e. their phenotype is not just intermediate, and there is some complementation of changes from the wildtype, but no complete reversal. 5) Wild-derived outbred populations kept in the laboratory diverge from wild mice over the course of a few generations, albeit less so than inbred mice. They are, however, not more divergent from each other than wild populations. This finding may point toward the existence of some epigenetically inherited mechanism of shape change which is somehow induced under laboratory conditions. 6) The Kerguelen mice, inbred strains, and wild-derived outbred populations (“derided populations”) do not diverge from wild mice in random directions. This pattern needs to be analyzed from a trait-based perspective. Geometric morphometrics alone is not suitable to dissect overall variation into individual traits. Simple alternative methods based on interlandmark distances (ILMDs) help to quantify the similarity between directions of shape change and to dissect shape changes with respect to the mandibular subregions involved. 7) Using a purpose-designed manual protocol, 20 groups of covarying ILMDs are identified, which can themselves be grouped into 5 “major traits”. These can largely be assumed to represent tradeoffs of tissue mass allocation during growth and to some degree functional coupling between parts of the mandible. 8) The 5 major traits explain large proportions of variation in several contexts: divergence of the derived populations from wild mice, variation within outbred and inbred populations (for the latter, i.e. developmental instability), “epistatic deviations” of outcross F1 from the interparental mean, and postnatal longitudinal ontogenetic shape change. This variety of contexts indicates that a large part of the genetically/developmentally generated variation is expressed via a limited number of types of shape changes. At the same time, the 5 traits are less important for the explanation of differences between populations and species. 9) Taking together the evidence for epistatic genetic architecture of shape and the results on the specific contexts in which the corresponding shape changes are observed, I hypothesize that epistatic shape variance may relate to developmental instability and provides the major part of phenotypic variance in wild populations. Stabilizing selection is unable to control this variation. Evolutionary divergence, however, happens predominantly along axes of additive variance, which provide a lower part of phenotypic variance within populations under this model, potentially due to the action of stabilizing selection

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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>We analyse here the genetic effects of chromosome substitution strains carrying <it>M. m. musculus </it>chromosomes in a largely <it>M. m. domesticus </it>background on mandible shape and compare them to the results of previously published QTL mapping data between <it>M. m. domesticus </it>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 <it>M. m. musculus </it>chromosomes is very different from the shape of the strain from which they were derived, as well as all known wild type shapes.</p> <p>Conclusions</p> <p>Our results suggest that the relative chromosome-wide effect sizes are comparable between the long separated subspecies <it>M. m. domesticus </it>and <it>M. m. musculus</it>, 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.</p

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

Micro-evolutionary divergence patterns of mandible shapes in wild house mouse (<it>Mus musculus</it>) populations

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>Using geometric morphometrics, we have surveyed mandible shapes in 15 natural populations of the genus <it>Mus</it>, with a focus on the subspecies <it>Mus musculus domesticus</it>. 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 <it>M. m. domesticus </it>and <it>M. spretus </it>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.</p> <p>Conclusions</p> <p>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.</p

EST based phylogenomics of Syndermata questions monophyly of Eurotatoria

Abstract 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.</p

EST based phylogenomics of Syndermata questions monophyly of Eurotatoria

Background: The metazoan taxon Syndermata comprising Rotifera (in the classical sense o