title: The mutational structure of metabolism in Caenorhabditis 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 mutation accumulation 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.
authors.affiliation: Department of Life Sciences, Imperial College London, United Kingdom.|Department of Surgery and Cancer, Imperial College London, United Kingdom.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Davies
authors.affiliation: Department of Life Sciences, Imperial College London, United Kingdom.
authors.forename: Armand
authors.initials: A
authors.lastname: Leroi
authors.affiliation: Department of Life Sciences, Imperial College London, United Kingdom.
authors.forename: Austin
authors.initials: A
authors.lastname: Burt
authors.affiliation: Department of Surgery and Cancer, Imperial College London, United Kingdom.
authors.forename: Jacob G
authors.initials: JG
authors.lastname: Bundy
authors.affiliation: Department of Biology, University of Florida, Gainesville, Florida. cbaer@ufl.edu.|Genetics Institute, University of Florida, Gainesville, Florida. cbaer@ufl.edu.
authors.forename: Charles F
authors.initials: CF
authors.lastname: Baer
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D056084:Genetic Fitness; D055442:Metabolome / Q000235:genetics*; D009154:Mutation; D000067552:Mutation Accumulation
keywords: Fitness; metabolome; mutation accumulation; mutational bias; mutational variance