Mutation, selection, and the prevalence of the Caenorhabditis elegans heat-sensitive mortal germline phenotype

Abstract

Caenorhabditis elegans strains with the heat-sensitive mortal germline phenotype become progressively sterile over the course of a few tens of generations when maintained at temperatures near the upper range of C. elegans’ tolerance. Mortal germline is transgenerationally heritable, and proximately under epigenetic control. Previous studies have suggested that mortal germline presents a relatively large mutational target and that mortal germline is not uncommon in natural populations of C. elegans. The mortal germline phenotype is not monolithic. Some strains exhibit a strong mortal germline phenotype, in which individuals invariably become sterile over a few generations, whereas other strains show a weaker (less penetrant) phenotype in which the onset of sterility is slower and more stochastic. We present results in which we (1) quantify the rate of mutation to the mortal germline phenotype and (2) quantify the frequency of mortal germline in a collection of 95 wild isolates. Over the course of ∼16,000 meioses, we detected one mutation to a strong mortal germline phenotype, resulting in a point estimate of the mutation rate UMrt≈ 6 × 10−5/genome/generation. We detected no mutations to a weak mortal germline phenotype. Six out of 95 wild isolates have a strong mortal germline phenotype, and although quantification of the weak mortal germline phenotype is inexact, the weak mortal germline phenotype is not rare in nature. We estimate a strength of selection against mutations conferring the strong mortal germline phenotype s¯≈0.1%, similar to selection against mutations affecting competitive fitness. The appreciable frequency of weak mortal germline variants in nature combined with the low mutation rate suggests that mortal germline may be maintained by balancing selection.

Genome‐wide association and environmental suppression of the mortal germline phenotype of wild C. elegans

“…We only used such polymorphisms in the GWAS (see Methods). We included data collected by Saber et al (2022) and used either the full strain set (Fig EV1B), or a restricted set (Fig 1E and F) without the divergent Pacific area strains (as defined by Crombie et al , 2019, and Lee et al , 2021, Table EV1). Using the restricted set of 113 strains, we found that variation in the number of generations to sterility was significantly associated with genetic variation in a region of chromosome III located around 5 Mb (Fig 1E).…”

“…Mutation accumulation lines can be used to measure the ease with which a given phenotype can be altered by de novo mutation and, by comparison with natural populations, allow inference of natural selection. With this aim in mind, Saber et al (2022) used spontaneous mutation accumulation lines in C. elegans starting from two wild‐derived strains with a non‐Mrt phenotype. They found a single mutation line with a strong Mrt phenotype, likely caused by a frameshifting insertion in nrde‐2 , and none with a weak Mrt phenotype.…”

“…Saber et al recently reported on the frequency of the Mrt phenotype in wild C. elegans isolates and its low mutational variance using mutation accumulation lines. They suggested that the phenotype—or the underlying genetic polymorphisms—may be under balancing selection (Saber et al , 2022). We here asked (i) whether we could detect a common polymorphism underlying the Mrt phenotype of C. elegans wild isolates; and (ii) whether the phenotype could be suppressed by natural environmental conditions.…”

Beyond the reference: gene expression variation and transcriptional response to RNAi inC. elegans

“…Antoine Cook et al, 2017;Crombie et al, 2019;Evans, van Wijk, et al, 2021;Gaertner & Phillips, 2010;Lee et al, 2021). Natural genetic variation exists for practically any organismal trait measurable in C. elegans (Andersen & Rockman, 2022), for example: responsiveness to toxins, metals, drugs, and other stressors (Dilks et al, 2021;Evans & Andersen, 2020;Evans, Wit, et al, 2021;Hahnel et al, 2018;Na et al, 2020;Webster et al, 2019;Zdraljevic et al, 2019;Zdraljevic et al, 2017); behavior (Bendesky et al, 2012;Ghosh et al, 2015;McGrath et al, 2009); transgenerational mortality traits (Frezal et al, 2018;Saber et al, 2022); and efficiency in RNA interference (RNAi) (Elvin et al, 2011;Felix, 2008;Felix et al, 2011;Paaby et al, 2015;Tijsterman et al, 2002).…”

“…However, C. elegans harbors significant intraspecific genetic diversity (A. Barriere & M. A. Felix, 2005; Antoine Barriere & M. A. Felix, 2005; Crombie et al, 2019; Lee et al, 2021; Andersen et al, 2012), and in the last decade C. elegans has also been established as a powerful system for elucidating connections between genotype and phenotype (Andersen et al, 2012; Andersen & Rockman, 2022; A. Barriere & M. A. Felix, 2005; Antoine Barriere & M. A. Felix, 2005; Cook et al, 2017; Crombie et al, 2019; Evans, van Wijk, et al, 2021; Gaertner & Phillips, 2010; Lee et al, 2021). Natural genetic variation exists for practically any organismal trait measurable in C. elegans (Andersen & Rockman, 2022), for example: responsiveness to toxins, metals, drugs, and other stressors (Dilks et al, 2021; Evans & Andersen, 2020; Evans, Wit, et al, 2021; Hahnel et al, 2018; Na et al, 2020; Webster et al, 2019; Zdraljevic et al, 2019; Zdraljevic et al, 2017); behavior (Bendesky et al, 2012; Ghosh et al, 2015; McGrath et al, 2009); transgenerational mortality traits (Frezal et al, 2018; Saber et al, 2022); and efficiency in RNA interference (RNAi) (Elvin et al, 2011; Felix, 2008; Felix et al, 2011; Paaby et al, 2015; Tijsterman et al, 2002).…”