In population samples, segregating recessive variants at low frequency are largely inaccessible to study. This project uses an experimental system in which rare alleles have been made common, recessive alleles can be homozygosed on demand, and cumulative effects of large numbers of small-effect variants can be measured in an unbiased way. The project centers on the nematode Caenorhabditis becei, which has all the experimental virtues of C. elegans but with a mating system and population biology that make it better suited to questions about genetic diversity in general and recessive variation in particular. This project will measure sex-specific competitive fitnesses and sex- and allele-specific transcript abundances in a specially designed panel of C. becei to reveal the architecture of segregating recessive variation and its molecular characteristics. The data will address basic questions in evolutionary biology while generating generalizable gene- and variant-scale models that predict whether variants are likely to have recessive effects.

Segregating recessive variants are responsible for a substantial health burden. The work proposed here interrogates the recessive effects of 2.4 million polymorphic sites segregating in an experimental nematode panel derived from six genomes freshly sampled from the wild. The data will generate generalizable gene- and variant-scale models that predict whether variants are likely to have recessive effects.