Spontaneous Mutations Decrease Sensitivity of Gene Expression to Random Environmental Variation in Caenorhabditis elegans

Abstract

BackgroundBiological phenotypes are described as “canalized” if they are robust to minor variation of environment and/or genetic background. The existence of a robust phenotype logically implies that some underlying mechanism must be variable, in the sense of “able to vary”, in order to compensate for variation in the environment and/or genetic effects. Several lines of evidence lead to the conclusion that deleterious mutations predictably render morphological, developmental, and life-history traits more sensitive to small random environmental perturbations - that is, mutations de-canalize the phenotype.Methodology/Principal FindingsUsing conventional dye-swap microarray methodology, we compared transcript abundance in a sample of >7,000 genes between four mutation accumulation (MA) lines of the nematode Caenorhabditis elegans and the common (unmutated) ancestor. There was significantly less environmental variance in the MA lines than in the ancestor, both among replicates of the same gene and among genes.Conclusions/SignificanceDeleterious mutations consistently decrease the within-line component of variance in transcript abundance, which is straightforwardly interpreted as reducing the sensitivity of gene expression to small random variation in the environment. This finding is consistent with the idea that underlying variability in gene expression might be mechanistically responsible for phenotypic robustness.

Evolution of a Higher Intracellular Oxidizing Environment in Caenorhabditis elegans under Relaxed Selection

“…Although the results of this study and results from other studies involving C. elegans [60], [61] and Drosophila [62] clearly show that strong and significant results can be detected with a small number of MA lines, there are several reasons why the failure to detect a strong relationship between oxidative stress and the frequency of base substitutions should not be surprising. First, the measures of oxidative stress reported here were measured at the endpoint of 250 generations of evolution under relaxed selection, whereas mutations accumulated in the genome over the entire 250 generations.…”

Global Gene Expression Divergence in Spontaneous Mutation Accumulation Lines ofCaenorhabditis elegansunder Varying Efficiency of Selection

“…As with the mutational variance, this suggests that mutations resulting in increased sensitivity to environmental and transcriptional noise due to dysregulation of gene expression are accumulating to the greatest degree under conditions of extreme genetic drift, and to a lesser degree in MA lines with larger population bottlenecks (and greater efficiency of selection). This increase in the Vr for transcription in our MA lines contrasts with a previous C. elegans study using DNA microarrays in which the ancestral N2 control was found to have higher Vr than the MA lines (Baer and Denver 2010). The observation that an increase in Vr largely mirrors the pattern for Vm suggests that the two may be related and perhaps stem from the same mechanistic causes.…”

“…This suggests that new mutations have rendered transcriptional regulation of some genes less robust and perhaps more sensitive to environmental variation. This contrasts with a previous C. elegans study in which the ancestral N2 control was found to have higher Vr than the MA lines (Baer and Denver 2010).…”

“…cerevisiae and D. melanogaster where mutational variation in gene expression was determined to be positively associated with environmental variation and gene expression noise (Rifkin et al 2005;Landry et al 2007;Huang et al 2016). The canalization of gene expression, which renders patterns of gene expression robust to the effects of environmental variation, also appears to buffer the perturbing effects of mutations by similar means (Wagner et al 1997;Meiklejohn and Hartl 2002;Rifkin et al 2005;Landry et al 2007;Baer and Denver 2010;Huang et al 2016).…”

“…The ratio of the mutational variance from MA studies to the environmental variance, Vm/Ve, has been used to estimate the mutational heritability and in the absence of experimental environmental variation, the residual variance, Vr, has sometimes been used as a proxy for Ve (Rifkin et al 2005). Following Baer and Denver (2010), we estimated Vr from the variance in gene expression between replicate plates of worms descended from the same MA genotype, wherein each plate housed several thousand L1 larvae. Although Ve should be based on individual variation, we assume that the Vr estimated from the variation among populations (plates) of the same genotype is a function of Ve, and can be used to indicate the relative magnitude of Ve between genotypes.…”