View Program - 2022 Population, Evolutionary, and Quantitative Genetics Conference

Segregating recessive variants have a substantial influence on biological processes. Outcrossing species tend to accumulate a high number of low-frequency moderately deleterious recessive variants, as their negative effects are masked by dominant alleles. Recessive variation has remained largely understudied, as low-frequency recessive variants have a small additive contribution, limiting statistical power in quantitative analyses. There is a need for an experimental system in which low-frequency variation can be made more common, recessive alleles can be made more homozygous, and recessive effects can be distinguished from additive effects. Here we present a new experimental evolve-and-resequencing approach to analyze recessive variants through the construction of recombinant inbred line crosses with varying degrees of relatedness and homozygosity. The gonochoristic nematode Caenorhabditis becei provides a powerful animal model for the study of recessive deleterious variation due to its ideal properties: Short generation time, the ability to cryopreserve living stocks and replicate genotypes, a small genome with a high-quality chromosome level assembly, and manageable levels of inbreeding depression, allowing us to create the first recombinant inbred panel for any gonochoristic Caenorhabditis. We have generated more than 400 recombinant inbred lines via 25 generations of sibmating starting from outbred wild founders. We have sequenced founding individuals, their F1 progeny, and all recombinant inbred lines. We are generating an annotated catalog of segregating variants, phasing haplotypes in the founder genomes, genotyping every recombinant inbred line, and characterizing the recessive deleterious variation exposed in our experimental evolution design.

Genetic Analysis of Segregating Recessive Variation in the Nematode Caenorhabditis becei