Genetic diversity estimates for the Caenorhabditis Intervention Testing Program screening panel.

Abstract

The Caenorhabditis Intervention Testing Program (CITP) was founded on the principle that compounds with positive effects across a genetically diverse test-set should have an increased probability of engaging conserved biochemical pathways with mammalian translational potential. To fulfill its mandate, the CITP uses a genetic diversity panel of Caenorhabditis strains for assaying longevity effects of candidate compounds. The panel comprises 22 strains from three different species, collected globally, to achieve inter-population genetic diversity. The three represented species, C. elegans, C. briggsae, and C. tropicalis, are all sequential hermaphrodites, which simplifies experimental procedures while maximizing intra-population homogeneity. Here, we present estimates of the genetic diversity encapsulated by the constituent strains in the panel based on their most recently published and publicly available whole-genome sequences, as well as two newly generated genomic data sets. We observed average genome-wide nucleotide diversity (π) within the C. elegans (1.2e-3), C. briggsae (7.5e-3), and C. tropicalis strains (2.6e-3) greater than estimates for human populations, and comparable to that found in mouse populations. Our analysis supports the assumption that the CITP screening panel encompasses broad genetic diversity, suggesting that lifespan-extending chemicals with efficacy across the panel should be enriched for interventions that function on conserved processes that are shared across genetic backgrounds. While the diversity panel was established by the CITP for studying longevity interventions, the panel may prove useful for the broader research community when seeking broadly efficacious interventions for any phenotype with potential genetic background effects.