"Evolutionary, developmental and functional aspects of skeletal variation in a mouse population selectively bred for increased long bone length"

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Phenotypic variation provides the fuel for evolution by means of selection. Despite this central role in the evolutionary process, several aspects of phenotypic variation remain poorly understood. These include: (i) the relationship between phenotypic variation and evolvability, (ii) the relationship between genetic, developmental and phenotypic variation in complex traits, and (iii) the relationship between phenotypic variation and variation in organismal function and performance. This proposal outlines an innovative research program that addresses these relationships in an integrative fashion, using artificial selection in mice. Through selective breeding for relative increases in tibia length, the program seeks to modify patterns of (co)variation in tibia length and correlated traits, and to create a population of mice with relatively longer tibiae compared to a control population. Three research objectives will be addressed: (1) to quantify how phenotypic and genetic correlations, and evolvability, change in traits under different selection pressures, (2) to uncover developmental and genetic differences that correlate with observed differences in tibia length between selected and control mice and (3) to assess the impact of increased tibia length on measures of musculoskeletal function and performance. To achieve these goals, we use an interdisciplinary approach, borrowing theory, concepts and practical tools from evolutionary quantitative genetics, developmental genetics and vertebrate functional morphology, and leveraging cutting-edge technologies such as µCT imaging and high-throughput transcriptome sequencing. The anticipated significance of this program is three-fold. First, it will improve our knowledge of how genetic and phenotypic variation are linked via organismal development. Second, it will create a novel mouse resource for integrative studies in skeletal biology. Third, and most importantly, by focusing on the mechanistic underpinnings of skeletal variation, this research will greatly advance our understanding of how skeletal variation drives evolutionary change and morphological diversity among vertebrates.