C. elegans toxicant responses vary among genetically diverse individuals

Abstract

Comprehensive chemical hazard risk evaluations require reproducible, efficient, and informative experimental workflows in tractable model systems that allow for high replication within exposure cohorts. Additionally, the genetic variability of toxicant responses among individuals in humans and mammalian models requires practically untenable sample sizes. Caenorhabditis elegans is a premier toxicology model that has revolutionized our understanding of cellular responses to environmental pollutants and boasts robust genomic resources and high levels of genetic variation across the species. In this study, we performed dose-response analysis across 23 environmental toxicants using eight C. elegans strains representative of species-wide genetic diversity. We observed substantial variation in EC10 estimates and slope parameter estimates of dose-response curves of different strains, demonstrating that genetic background is a significant driver of differential toxicant susceptibility. We also showed that, across all toxicants, at least one C. elegans strain exhibited a significantly different EC10 or slope estimate compared to the reference strain, N2 (PD1074), indicating that population-wide differences among strains are necessary to understand responses to toxicants. Moreover, we quantified the heritability of responses to each toxicant dose and observed a correlation between the dose closest to the species-agnostic EC10 estimate and the dose that exhibited the most heritable response. Taken together, these results provide robust evidence that heritable genetic variation explains differential susceptibility across an array of environmental pollutants and that genetically diverse C. elegans strains should be deployed to aid high-throughput toxicological screening efforts.