The role of developmental genetic architecture in shaping evolutionary trends – DevEvolTrends

Mutation is the ultimate source of phenotypic variation in evolution. Random mutation, however, does not translate into isotropic phenotypic variation in all directions of phenotype space because development limits or biases the mutationally inducible phenotypic spectrum. Hence, this mutationally inducible phenotypic spectrum is fundamental in determining the potential phenotypic trajectories that can be explored by evolution. Whether and how such biases in the introduction of phenotypic variation may influence evolutionary trends – particular directions of evolutionary variation in the phenotypic space – remain extremely poorly understood. In the proposed project, we aim to generate comprehensive empirical insights into the nature and evolution of mutational variance of a developmental system.
Our main objectives will integrate the use of random mutation lines, quantitative genetics and developmental analyses to explore whether and how differential mutational sensitivity of specific cell fates adopted during development can explain their divergent evolutionary patterns within and between species. As a model system, we will study variation in the fates of six homologous cells that can be found across nematode taxa, the vulval precursor cells, termed P3.p to P8.p according to their antero-posterior position in the ventral epidermis of larvae. Importantly, the developmental fates of these six cells show distinct evolutionary patterns in two clades of nematodes: in the Caenorhabditis genus, the cell fate of P3.p varies the most across evolution; in contrast, the fates of P4.p and P8.p vary the most in the Oscheius genus. Therefore, the evolutionary trends in P(3-8).p fates differ between these two nematode genera. We previously showed that in two tested species of Caenorhabditis, the cell fate of P3.p was the most sensitive to random mutation, thus matching the observed evolutionary trend in the genus. Here we hypothesize that the differences in observed evolutionary trends between the Caenorhabditis and Oscheius genus are due in part to differential mutability at the phenotypic level (evolution of mutational variances) through the developmental genetic architecture, depending on species and genetic background.
Specifically, we propose (1) to quantify and compare the mutability of these six cell fates by building and phenotyping random mutation lines derived from wild isolates of both Caenorhabditis and Oscheius, (2) to connect these experimental data with patterns of intraspecific and interspecific variation in these traits using a large array of wild isolates in the two genera and studying the genetic architecture of natural variation within a species, and (3) to characterize the developmental genetic basis for this differential mutability by determining causal mutations in the mutation lines and then using them for reciprocal mutations of homologous genes and developmental measurements. Identification of the mutationally most sensitive features of the vulval developmental system will indicate axes of potential evolutionary variation. We will then be able to compare these results with actually observed evolutionary trends, allowing us to determine the relative roles of mutation versus selection in shaping evolutionary trends. The results will be among the first to causally connect mutability (mutational variance), developmental biology and evolutionary trends, while contrasting trends in two clades. Our experimental approach is unique as it integrates molecular, developmental and evolutionary genetic analysis at the single-cell level.