Genetic architecture of craniofacial shape in the house mouse: a genetic and morphological perspective

Morphological diversity in nature is astounding. A remarkable example of such diversity is the vertebrate cranium. This structure is developmentally, anatomically, and functionally integrated with the many other tissues and sensory systems of the head. Because of this, it is under strong constrains to achieve an adult form (size and shape) compatible with the functional requirements of the individual. The genetic basis of craniofacial diversity has been traditionally studied from a macro-evolutionary perspective (i.e. at the between-species level), with special focus on adaptive radiation and domestication. The work presented in this thesis is an attempt to understand the genetic basis of craniofacial shape variation in the house mouse. By using between-subspecies and within population variation, I address the question from a micro-evolutionary perspective. In this thesis I also explore the genetic architecture of the traits (i.e. number, effect size, and genomic distribution of the causal loci), and the extent to which phenotypic variation can be explained by genetic variation – i.e. heritability of the traits. The first two chapters of this thesis are the first genome-wide approximation to the genetic architecture of craniofacial shape and size in mice. I combine highly recombinant mouse populations –wild hybrid mice and outbred lab mice- with dense marker coverage of the genome to map the loci underlying phenotypic variation. I identify genes previously known to be involved in craniofacial formation, and provide a list of genomic regions that contain new candidate genes for craniofacial development. Regarding the genetic architecture, I show that craniofacial traits are highly polygenic and highly heritable, with many loci of very small effect distributed uniformly along the genome. The last chapter of the thesis is an assessment of the morphological transition associated with the degree of admixture between two subspecies of the house mouse, Mus musculus musculus and Mus musculus domesticus. I show that craniofacial shape changes, but not size changes, are correlated with the level of admixture. The transition from M. m. musculus to M. m. domesticus is continuous, such mode would be expected from a trait with polygenic architecture, and therefore these results are in line with the genetic results obtained in previous chapters. Overall the work presented in this thesis is the first genome-wide analyses of the genetic basis and genetic architecture of craniofacial shape variation in the house mouse. It is also the first time shape variation is explored in a close-to-natural context; previous work used crosses between inbred 10 mouse strains. Therefore, the results reported here are directly relevant to the understanding of complex traits evolution