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

Citation

Baer, Charles; Johnson, Lindsay; Hahn, Daniel; Smith, Olivia (2020), Short-term heritable variation overwhelms two hundred generations of mutational variance for metabolic traits in Caenorhabditis elegans, Dryad, Dataset, https://doi.org/10.5061/dryad.9cnp5hqgb

Abstract

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.

Methods

Data are raw data as described in the Methods of the publication and have not been normalized.

Usage Notes

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:

  1. Random; A random number associated with each replicate, from 1-290.
  2. Extraction_block; extraction block 1-5, see Methods for details.
  3. Tr; Treatment=MA (mutation accumulation) or PS (ancestral pseudoline)
  4. Line; line number (MA or ancestral pseudoline)
  5. Rep; replicate number (1-5)
  6. 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.
  7. ADAblock; Adenosine deaminase (ADA) activity assay block (1-4).
  8. ADKblock; Adenosine kinase (ADK) activity assay block (1-5).
  9. Tot_Pro; Total soluble protein concentration.
  10. ADA_act; Adenosine deaminase (ADA) activity.
  11. ADK_act; Adenosine kinase (ADK) activity.
  12. TubADA; Tubulin concentration, measured in the ADA assay.
  13. ADA_conc; ADA concentration.
  14. TubADK; Tubullin concentration, measured in the ADK assay.
  15. ADK_conc; ADK concentration.
  16. AMP; concentration of adenosine monophosphate (AMP).
  17. Adenine; concentration of adenine.
  18. Adenosine; concentration of adenosine.
  19. GMP; concentration of guanosine monophosphate.
  20. Guanine; concentration of guanine.
  21. Guanosine; concentration of guanosine.
  22. Hypoxanthine; concentration of hypoxanthine.
  23. Uric_Acid; concentration of uric acid.
  24. Xanthine; concentration of xanthine.
  25. Inosine; concentration of inosine.

Funding

National Institutes of Health, Award: GM107227, R25GM115298

National Science Foundation, Award: DEB 1639005

University of Florida, Award: UFGI seed grant