Letter

Maternal age generates phenotypic variation in Caenorhabditis elegans

Received:
Accepted:
Published online:

Abstract

Genetically identical individuals that grow in the same environment often show substantial phenotypic variation within populations of organisms as diverse as bacteria1, nematodes2, rodents3 and humans4. With some exceptions5,6,7, the causes are poorly understood. Here we show that isogenic Caenorhabditis elegans nematodes vary in their size at hatching, speed of development, growth rate, starvation resistance, fecundity, and also in the rate of development of their germline relative to that of somatic tissues. We show that the primary cause of this variation is the age of an individual’s mother, with the progeny of young mothers exhibiting several phenotypic impairments. We identify age-dependent changes in the maternal provisioning of the lipoprotein complex vitellogenin to embryos as the molecular mechanism that underlies the variation in multiple traits throughout the life of an animal. The production of sub-optimal progeny by young mothers may reflect a trade-off between the competing fitness traits of a short generation time and the survival and fecundity of the progeny.

  • Subscribe to Nature for full access:

    $199

    Subscribe

Additional access options:

Already a subscriber?  Log in  now or  Register  for online access.

Accessions

Primary accessions

Gene Expression Omnibus

References

  1. 1.

    & Non-genetic individuality: chance in the single cell. Nature 262, 467–471 (1976)

  2. 2.

    et al. What accounts for the wide variation in life span of genetically identical organisms reared in a constant environment? Mech. Ageing Dev. 126, 439–443 (2005)

  3. 3.

    A third component causing random variability beside environment and genotype. A reason for the limited success of a 30 year long effort to standardize laboratory animals? Lab. Anim. 24, 71–77 (1990)

  4. 4.

    , & Phenotypic differences in genetically identical organisms: the epigenetic perspective. Hum. Mol. Genet. 14, R11–R18 (2005)

  5. 5.

    , , & Variability in gene expression underlies incomplete penetrance. Nature 463, 913–918 (2010)

  6. 6.

    , & Predicting mutation outcome from early stochastic variation in genetic interaction partners. Nature 480, 250–253 (2011)

  7. 7.

    , & Fitness trade-offs and environmentally induced mutation buffering in isogenic C. elegans. Science 335, 82–85 (2012)

  8. 8.

    & The effects of genetic variation on gene expression dynamics during development. Nature 505, 208–211 (2014)

  9. 9.

    & Heterochronic mutants of the nematode Caenorhabditis elegans. Science 226, 409–416 (1984)

  10. 10.

    et al. Complex heterochrony underlies the evolution of Caenorhabditis elegans hermaphrodite sex allocation. Evolution 70, 2357–2369 (2016)

  11. 11.

    & Influence of parental aging on the reproduction of the F1 in a hermaphrodite nematode Caenorhabditis elegans. Exp. Gerontol. 7, 195–206 (1972)

  12. 12.

    et al. A novel sperm-delivered toxin causes late-stage embryo lethality and transmission ratio distortion in C. elegans. PLoS Biol. 9, e1001115 (2011)

  13. 13.

    , & Maternal effects mediated by maternal age: from life histories to population dynamics. J. Anim. Ecol. 77, 1038–1046 (2008)

  14. 14.

    & The mysterious case of the C. elegans gut granule: death fluorescence, anthranilic acid and the kynurenine pathway. Front. Genet. 4, 151 (2013)

  15. 15.

    et al. Quantitative assessment of fat levels in Caenorhabditis elegans using dark field microscopy. G3 (Bethesda) 7, 1811–1818 (2017)

  16. 16.

    Aging in the nematode Caenorhabditis elegans: major biological and environmental factors influencing life span. Mech. Ageing Dev. 6, 413–429 (1977)

  17. 17.

    , , , & Arresting development arrests aging in the nematode Caenorhabditis elegans. Mech. Ageing Dev. 28, 23–40 (1984)

  18. 18.

    , , & The laboratory domestication of Caenorhabditis elegans. Trends Genet. 31, 224–231 (2015)

  19. 19.

    & Tissue-specific synthesis of yolk proteins in Caenorhabditis elegans. Dev. Biol. 96, 189–196 (1983)

  20. 20.

    & Receptor-mediated endocytosis in the Caenorhabditis elegans oocyte. Mol. Biol. Cell 10, 4311–4326 (1999)

  21. 21.

    , , , & TBC-2 is required for embryonic yolk protein storage and larval survival during L1 diapause in Caenorhabditis elegans. PLoS ONE 5, e15662 (2010)

  22. 22.

    , , , & New genetic regulators question relevance of abundant yolk protein production in C. elegans. Sci. Rep. 5, 16381 (2015)

  23. 23.

    , , , & Two distinct yolk lipoprotein complexes from Caenorhabditis elegans. J. Biol. Chem. 265, 14422–14431 (1990)

  24. 24.

    , , , & TGF-β and insulin signaling regulate reproductive aging via oocyte and germline quality maintenance. Cell 143, 299–312 (2010)

  25. 25.

    et al. Starvation-induced transgenerational inheritance of small RNAs in C. elegans. Cell 158, 277–287 (2014)

  26. 26.

    et al. Transgenerational effects of early life starvation on growth, reproduction, and stress resistance in Caenorhabditis elegans. Genetics 201, 201–212 (2015)

  27. 27.

    & All eggs are not equal: the maternal environment affects progeny reproduction and developmental fate in Caenorhabditis elegans. PLoS ONE 6, e25840 (2011)

  28. 28.

    , , , & Transgenerational transmission of environmental information in C. elegans. Science 356, 320–323 (2017)

  29. 29.

    et al. Impaired DNA replication derepresses chromatin and generates a transgenerationally inherited epigenetic memory. Sci. Adv. 3, e1701143 (2017)

  30. 30.

    & More is not better: brood size and population growth in a self-fertilizing nematode. Proc. R. Soc. Lond. B 246, 19–24 (1991)

  31. 31.

    , , , & Streamlined genome engineering with a self-excising drug selection cassette. Genetics 200, 1035–1049 (2015)

  32. 32.

    , & Morphologically defined sub-stages of C. elegans vulval development in the fourth larval stage. BMC Dev. Biol. 15, 26 (2015)

  33. 33.

    , & Comparing median lethal concentration values using confidence interval overlap or ratio tests. Environ. Toxicol. Chem. 25, 1441–1444 (2006)

  34. 34.

    et al. CellProfiler: image analysis software for identifying and quantifying cell phenotypes. Genome Biol. 7, R100 (2006)

  35. 35.

    et al. An image analysis toolbox for high-throughput C. elegans assays. Nat. Methods 9, 714–716 (2012)

  36. 36.

    et al. Fluorescence-based fixative and vital staining of lipid droplets in Caenorhabditis elegans reveal fat stores using microscopy and flow cytometry approaches. J. Lipid Res. 52, 1281–1293 (2011)

  37. 37.

    et al. Regulation of Caenorhabditis elegans vitellogenesis by DAF-2/IIS through separable transcriptional and posttranscriptional mechanisms. BMC Physiol. 11, 11 (2011)

  38. 38.

    , & Density dependence in Caenorhabditis larval starvation. Sci. Rep. 3, 2777 (2013)

  39. 39.

    , , , & Metabolic rate regulates L1 longevity in C. elegans. PLoS ONE 7, e44720 (2012); erratum 8, (2013)

  40. 40.

    & Assessing aging and senescent decline in Caenorhabditis elegans: cohort survival analysis. Methods Mol. Biol. 965, 473–484 (2013)

  41. 41.

    et al. RNAi interrogation of dietary modulation of development, metabolism, behavior, and aging in C. elegans. Cell Reports 11, 1123–1133 (2015)

  42. 42.

    & Genome-wide RNAi screening in Caenorhabditis elegans. Methods 30, 313–321 (2003)

  43. 43.

    , & Relationship between mitochondrial electron transport chain dysfunction, development, and life extension in Caenorhabditis elegans. PLoS Biol. 5, e259 (2007)

  44. 44.

    et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 3, research0034.1 (2002)

  45. 45.

    et al. GETPrime: a gene- or transcript-specific primer database for quantitative real-time PCR. Database (Oxford) 2011, bar040 (2011)

  46. 46.

    , , & Genome-wide germline-enriched and sex-biased expression profiles in Caenorhabditis elegans. Development 131, 311–323 (2004)

  47. 47.

    , & Selection at linked sites shapes heritable phenotypic variation in C. elegans. Science 330, 372–376 (2010)

  48. 48.

    et al. A spatial and temporal map of C. elegans gene expression. Genome Res. 21, 325–341 (2011)

  49. 49.

    , , & Global prediction of tissue-specific gene expression and context-dependent gene networks in Caenorhabditis elegans. PLOS Comput. Biol. 5, e1000417 (2009)

  50. 50.

    & Principal curves. J. Am. Stat. Assoc. 84, 502–516 (1989)

  51. 51.

    , , & emo-1, a Caenorhabditis elegans Sec61p gamma homologue, is required for oocyte development and ovulation. J. Cell Biol. 134, 699–714 (1996)

  52. 52.

    et al. The gut esterase gene (ges-1) from the nematodes Caenorhabditis elegans and Caenorhabditis briggsae. J. Mol. Biol. 229, 890–908 (1993)

Download references

Acknowledgements

This work was supported by a European Research Council Consolidator grant (616434), the Spanish Ministry of Economy and Competitiveness (BFU2011-26206 and SEV-2012-0208), the AXA Research Fund, the Bettencourt Schueller Foundation, Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR, 2014 SGR 831), the EMBL-CRG Systems Biology Program, and the CERCA Program/Generalitat de Catalunya. M.F.P. was partially supported by a FPI-Severo Ochoa fellowship. Expression profiling was performed in the CRG Genomics core facility and microscopy in the CRG Advanced Light Microscopy Facility. Some strains were provided by the CGC, which is funded by National Institutes of Health Office of Research Infrastructure Programs (P40 OD010440).

Author information

Author notes

    • Marcos Francisco Perez
    •  & Mirko Francesconi

    These authors contributed equally to this work.

Affiliations

  1. EMBL-CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain.

    • Marcos Francisco Perez
    • , Mirko Francesconi
    • , Cristina Hidalgo-Carcedo
    •  & Ben Lehner
  2. Universitat Pompeu Fabra (UPF), Barcelona, Spain

    • Marcos Francisco Perez
    • , Mirko Francesconi
    • , Cristina Hidalgo-Carcedo
    •  & Ben Lehner
  3. Institució Catalana de Recerca i Estudis Avançats (ICREA), Pg. Lluis Companys 23, Barcelona 08010, Spain.

    • Ben Lehner

Authors

  1. Search for Marcos Francisco Perez in:

  2. Search for Mirko Francesconi in:

  3. Search for Cristina Hidalgo-Carcedo in:

  4. Search for Ben Lehner in:

Contributions

M.F.P., M.F. and B.L. conceived the model, designed experiments and wrote the manuscript. M.F.P., M.F. and C.H.-C. performed experiments and analysed the data.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Ben Lehner.

Reviewer Information Nature thanks D. Gems, O. Rechavi and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Extended data

Supplementary information

PDF files

  1. 1.

    Life Sciences Reporting Summary

  2. 2.

    Supplementary Figure 1

    This file contains he uncropped source data for the gel shown in Extended Data Figure 4h.

Excel files

  1. 1.

    Supplementary Tables 1 and 2

    This file contains table 1 (supplementary to Fig. 1). Table including projection of single worm expression profiles onto the germline and somatic expression spaces and their germline and soma ranking. It also contains table 2 (supplementary to Extended Data Fig. 1). Table including residuals of single worm gene expression after correcting for germline and soma developmental stage. The table also indicates for each gene whether germline or somatic ranking better explains the observed variation and includes gene annotation for the tissue-specific gene sets. Both tables are combined as separate sheets in a single .xlsx file.

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.