The mutational structure of metabolism inCaenorhabditis elegans

Abstract

A properly functioning organism must maintain metabolic homeostasis. Deleterious mutations degrade organismal function, presumably at least in part via effects on metabolic function. Here we present an initial investigation into the mutational structure of the Caenorhabditis elegans metabolome by means of a mutation accumulation experiment. We find that pool sizes of 29 metabolites vary greatly in their vulnerability to mutation, both in terms of the rate of accumulation of genetic variance (the mutational variance, VM) and the rate of change of the trait mean (the mutational bias, ΔM). Strikingly, some metabolites are much more vulnerable to mutation than any other trait previously studied in the same way. Although we cannot statistically assess the strength of mutational correlations between individual metabolites, principal component analysis provides strong evidence that some metabolite pools are genetically correlated, but also that there is substantial scope for independent evolution of different groups of metabolites. Averaged over MA lines, PC3 is positively correlated with relative fitness, but a model in which metabolites are uncorrelated with fitness is nearly as good by Akaike's Information Criterion (AIC).

How does mutation affect the distribution of phenotypes?

“…Although we lacked the power to fully explore the affect of mutation on the distribution of variation across phenotypic space we note that the major axis of relative difference in variance between control and mutant males (d 1 ) reflected variation in multiple body shape traits (Table 1). Uneven distribution of mutational variance across phenotypic space has been reported previously for morphology, gene expression, locomotor performance, and metabolites (Houle and Fierst 2013;Latimer et al 2014;McGuigan et al 2014;Davies et al 2016), suggesting that mutation might typically bias the distribution of variation available to evolution.…”

“…In contrast to the expectation of bias for fitness, traits not closely associated with fitness are predicted to show no change in population mean under mutation (Johnson and Barton 2005). Again, available evidence is mixed; some studies reported no mutational effects on trait mean of nonfitness traits (Santiago et al 1992;Camara et al 2000;Houle and Fierst 2013;Stearns and Fenster 2016), while other studies reported mutational bias (Camara et al 2000;McGuigan and Blows 2013;Davies et al 2016). The potential for mutation to shift population trait means requires further investigation across different types of traits and taxa to determine whether mutational biases on trait mean might be common, and what types of traits might typically be affected.…”

“…A variety of experimental approaches have provided evidence of pervasive pleiotropic effects of new mutations (Denver et al 2005;Estes et al 2005;Rifkin et al 2005;Estes and Phillips 2006;McGuigan et al 2014;Gerstung et al 2015;Davies et al 2016;Utrilla et al 2016). Mutational covariances among traits have been estimated relatively rarely; available evidence suggests mutation generates positive covariance among life history traits (e.g., Houle et al 1994;Estes et al 2005).…”

“…Several studies have investigated the mutational variance in performance traits, including body size (which is often considered a performance trait: Franklin and Morrissey 2017), with mixed evidence: some studies supported the hypothesis that mutation decreases mean performance (Keightley and Ohnishi 1998;Yang et al 2001;Azevedo et al 2002;Estes et al 2005;Ostrow et al 2007;Herdegen and Radwan 2015), while other studies rejected this hypothesis (Huey et al 2003;McGuigan and Blows 2013;Latimer et al 2014). Again, available evidence is mixed; some studies reported no mutational effects on trait mean of nonfitness traits (Santiago et al 1992;Camara et al 2000;Houle and Fierst 2013;Stearns and Fenster 2016), while other studies reported mutational bias (Camara et al 2000;McGuigan and Blows 2013;Davies et al 2016). Again, available evidence is mixed; some studies reported no mutational effects on trait mean of nonfitness traits (Santiago et al 1992;Camara et al 2000;Houle and Fierst 2013;Stearns and Fenster 2016), while other studies reported mutational bias (Camara et al 2000;McGuigan and Blows 2013;Davies et al 2016).…”

Short-term heritable variation overwhelms two hundred generations of mutational variance for metabolic traits inCaenorhabditis elegans

“…More recently, DAVIES et al (2016) examined the changes in metabolite concentration 74 for 29 metabolites in a set of C. elegans MA lines that had undergone ~250 generations of 75 evolution under minimal selection and found that metabolites vary considerably in their 76 response to spontaneous mutation, as quantified by the change in mean metabolite 77 concentration (ΔM) and by the mutational (co)variance. Associations between mutational 78 correlations between pairs of metabolites (rM, presumably the result of pleiotropy) and proximity 79 of the metabolites in the global metabolic network were, on average, positive but weak 80 (JOHNSON et al 2018).…”