Insulin-like peptides and the mTOR-TFEB pathway protect C. elegans hermaphrodites from Mating-induced Death

  1. Cheng Shi
  2. Lauren N Booth
  3. Coleen T Murphy  Is a corresponding author
  1. Princeton University, United States
  2. Stanford University, United States

Abstract

C. elegans lifespan is shortened by mating, but these deleterious effects must be delayed long enough for successful reproduction. Susceptibility to brief mating-induced death is caused by the loss of protection upon self-sperm depletion. Self-sperm maintains the expression of a DAF-2 insulin-like antagonist, INS-37, which promotes the nuclear localization of intestinal HLH-30/TFEB, a key pro-longevity regulator. Mating induces the agonist INS-8, promoting HLH-30 nuclear exit and subsequent death. In opposition to the protective role of HLH-30 and DAF-16/FOXO, TOR/LET-363 and the IIS-regulated Zn-finger transcription factor PQM-1 promote seminal-fluid-induced killing. Self-sperm maintenance of nuclear HLH-30/TFEB allows hermaphrodites to resist mating-induced death until self-sperm are exhausted, increasing the chances that mothers will survive through reproduction. Mothers combat males' hijacking of their IIS pathway by expressing an insulin antagonist that keeps her healthy through the activity of pro-longevity factors, as long as she has her own sperm to utilize.

Data availability

Microarray data are available at the following links:"L4 fog-2(q71) vs N2 hermaphrodites"https://puma.princeton.edu/cgi-bin/exptsets/review.pl?exptset_no=7332"L4 fem-3(q20) vs N2 hermaphrodites"https://puma.princeton.edu/cgi-bin/exptsets/review.pl?exptset_no=7333"D3 mated fog-2(q71) vs pqm-1(ok485) hermaphrodites"https://puma.princeton.edu/cgi-bin/exptsets/review.pl?exptset_no=7334

Article and author information

Author details

  1. Cheng Shi

    Department of Molecular Biology, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0365-8273
  2. Lauren N Booth

    Department of Genetics, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Coleen T Murphy

    Department of Molecular Biology, Princeton University, Princeton, United States
    For correspondence
    ctmurphy@princeton.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8257-984X

Funding

NIH Office of the Director (Pioneer 1DP1OD020400-01)

  • Coleen T Murphy

Glenn Foundation for Medical Research (NA)

  • Coleen T Murphy

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Matt Kaeberlein, University of Washington, United States

Publication history

  1. Received: February 27, 2019
  2. Accepted: July 7, 2019
  3. Accepted Manuscript published: July 8, 2019 (version 1)
  4. Version of Record published: August 16, 2019 (version 2)

Copyright

© 2019, Shi et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Cheng Shi
  2. Lauren N Booth
  3. Coleen T Murphy
(2019)
Insulin-like peptides and the mTOR-TFEB pathway protect C. elegans hermaphrodites from Mating-induced Death
eLife 8:e46413.
https://doi.org/10.7554/eLife.46413

Further reading

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    2. Genetics and Genomics
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    Insight

    Young Caenorhabditis elegans hermaphrodites use their own sperm to protect against the negative consequences of mating.

    1. Evolutionary Biology
    2. Genetics and Genomics
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    Research Article Updated

    Meiotic drive supergenes are complexes of alleles at linked loci that together subvert Mendelian segregation resulting in preferential transmission. In males, the most common mechanism of drive involves the disruption of sperm bearing one of a pair of alternative alleles. While at least two loci are important for male drive—the driver and the target—linked modifiers can enhance drive, creating selection pressure to suppress recombination. In this work, we investigate the evolution and genomic consequences of an autosomal, multilocus, male meiotic drive system, Segregation Distorter (SD) in the fruit fly, Drosophila melanogaster. In African populations, the predominant SD chromosome variant, SD-Mal, is characterized by two overlapping, paracentric inversions on chromosome arm 2R and nearly perfect (~100%) transmission. We study the SD-Mal system in detail, exploring its components, chromosomal structure, and evolutionary history. Our findings reveal a recent chromosome-scale selective sweep mediated by strong epistatic selection for haplotypes carrying Sd, the main driving allele, and one or more factors within the double inversion. While most SD-Mal chromosomes are homozygous lethal, SD-Mal haplotypes can recombine with other, complementing haplotypes via crossing over, and with wildtype chromosomes via gene conversion. SD-Mal chromosomes have nevertheless accumulated lethal mutations, excess non-synonymous mutations, and excess transposable element insertions. Therefore, SD-Mal haplotypes evolve as a small, semi-isolated subpopulation with a history of strong selection. These results may explain the evolutionary turnover of SD haplotypes in different populations around the world and have implications for supergene evolution broadly.