DOI: 10.5061/dryad.9cnp5hqgb
title: Short-term heritable variation overwhelms two hundred generations of mutational variance for metabolic traits in Caenorhabditis elegans

description: Metabolic disorders have a large heritable component, and have increased
 markedly in human populations over the past few generations. 
 Genome-wide association studies of metabolic traits typically find a
 substantial unexplained fraction of total heritability, suggesting an
 important role of spontaneous mutation.  An alternative
 explanation is that epigenetic effects contribute significantly to the
 heritable variation. Here we report a study designed to quantify the
 cumulative effects of spontaneous mutation on adenosine metabolism in the
 nematode Caenorhabditis elegans, including both the activity and
 concentration of two metabolic enzymes and the standing pools of their
 associated metabolites.  The only prior studies on the effects of
 mutation on metabolic enzyme activity, in Drosophila melanogaster, found
 that total enzyme activity presents a mutational target similar to that of
 morphological and life-history traits.  However, those studies
 were not designed to account for short-term heritable effects. 
 We find that the short-term heritable variance for most traits is of
 similar magnitude as the variance among MA lines.  This result
 suggests that the potential heritable effects of epigenetic variation in
 metabolic disease warrant additional scrutiny.
description: Data are raw data as described in the Methods of the publication
 and have not been normalized.
description: Raw (not normalized) data
 for enzyme activity, protein concentration, and metabolite
 concentrations.  See Methods in the main text for details.  Column
 headings (A-Y) in the worksheet titled "Data" are:
 
 Random; A random number associated with each replicate, from
 1-290. Extraction_block; extraction block 1-5, see
 Methods for details. Tr; Treatment=MA (mutation
 accumulation) or PS (ancestral pseudoline) Line; line
 number (MA or ancestral pseudoline) Rep; replicate
 number (1-5) techrep; Technical replicate, nested
 within replicate.  All traits except adenosine kinase activity (ADK_act)
 and several replicates of adenosine deaminase concentration (ADA_conc)
 have only one technical replicate.  For ADK_act and ADA_conc, technical
 replicates were averaged for each (biological) replicate prior to
 downstream analyses. ADAblock; Adenosine deaminase
 (ADA) activity assay block (1-4). ADKblock; Adenosine
 kinase (ADK) activity assay block (1-5). Tot_Pro;
 Total soluble protein concentration. ADA_act; Adenosine deaminase (ADA)
 activity. ADK_act; Adenosine kinase (ADK)
 activity. TubADA; Tubulin concentration, measured in
 the ADA assay. ADA_conc; ADA
 concentration. TubADK; Tubullin
 concentration, measured in the ADK assay. ADK_conc;
 ADK concentration. AMP; concentration of adenosine
 monophosphate (AMP). Adenine; concentration of
 adenine. Adenosine; concentration of
 adenosine. GMP; concentration of guanosine
 monophosphate. Guanine; concentration of
 guanine. Guanosine; concentration of
 guanosine. Hypoxanthine; concentration of
 hypoxanthine. Uric_Acid;
 concentration of uric acid. Xanthine; concentration of xanthine.
 Inosine; concentration of inosine.