A Test for Epistasis Among Induced Mutations in Caenorhabditis elegans

Abstract

Synergistic epistasis, in which deleterious mutations tend to magnify each other’s effects, is a necessary component of the mutational deterministic hypothesis for the maintenance of sexual production. We tested for epistasis for life-history traits in the soil nematode Caenorhabditis elegans by inducing mutations in two genetic backgrounds: a wild-type strain and a set of genetically loaded lines that contain large numbers of independent mildly detrimental mutations. There was no significant difference between the effect of new mutations on the wild-type background and the genetically loaded background for four out of five fitness correlates. In these four cases, the maximum level of epistasis compatible with the data was very low. The fifth trait, late productivity, is not likely to be an important component of fitness. This suggests either that specific environmental conditions are required to cause epistasis or that synergistic epistasis is not a general phenomenon. We also suggest a new mechanism by which deleterious mutations may provide an advantage to sexual reproduction under low selection coefficients.

Variation in mutational (co)variances

“…Mutational bias occurs when the distribution of phenotypic effects depends on genetic background and thus when there are non-additive and epistatic effects between the de novo MA and the fixed genetic background ( Halligan and Keightley 2009 ; Jones et al 2014 ; Saxena et al 2018 ; Schweizer and Wagner 2020 ). In our case, however, one should be cautious in interpreting the presence of epistasis because the phenotypic effect distribution of new mutations was barely sampled ( Keightley et al 2000 ; Peters and Keightley 2000 ; Jasmin and Lenormand 2016 ). Given the number of generations in any MA experiment and the small number of lines assayed here, each MA line carries an idiosyncratic number of mutations that do not comprehensibly target the QTL underlying presumed polygenic traits such as locomotion behavioral traits.…”

Variation in mutational (co)variances

“…Mutational bias could be interpreted to reveal epistasis (Halligan and Keightley, 2009; Jones et al, 2014; Saxena et al, 2018; Schweizer and Wagner, 2020), as the distribution of phenotypic effects depends on genetic background. However, with just two genotypes, and because MA lines carry a small and heterogeneous sample of mutations between them, the phenotypic effect distribution of mutations is barely sampled and any firm conclusion regarding epistasis remains unsupported (Jasmin and Lenormand, 2016; Keightley et al, 2000; Peters and Keightley, 2000).…”