1. Genetics and Genomics
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Wild worm embryogenesis harbors ubiquitous polygenic modifier variation

Research Article
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Cite this article as: eLife 2015;4:e09178 doi: 10.7554/eLife.09178

Abstract

Embryogenesis is an essential and stereotypic process that nevertheless evolves among species. Its essentiality may favor the accumulation of cryptic genetic variation (CGV) that has no effect in the wild-type but that enhances or suppresses the effects of rare disruptions to gene function. Here, we adapted a classical modifier screen to interrogate the alleles segregating in natural populations of C. elegans: we induced gene knockdowns and used quantitative genetic methodology to examine how segregating variants modify the penetrance of embryonic lethality. Each perturbation revealed CGV, indicating that wild-type genomes harbor myriad genetic modifiers that may have little effect individually but which in aggregate can dramatically influence penetrance. Phenotypes were mediated by many modifiers, indicating high polygenicity, but the alleles tend to act very specifically, indicating low pleiotropy. Our findings demonstrate the extent of conditional functionality in complex trait architecture.

Article and author information

Author details

  1. Annalise B Paaby

    Department of Biology and Center for Genomics and Systems Biology, New York University, New York, United States
    For correspondence
    apaaby@nyu.edu
    Competing interests
    The authors declare that no competing interests exist.
  2. Amelia G White

    Department of Biology and Center for Genomics and Systems Biology, New York University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. David D Riccardi

    Department of Biology and Center for Genomics and Systems Biology, New York University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Kristin C Gunsalus

    Department of Biology and Center for Genomics and Systems Biology, New York University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Fabio Piano

    Department of Biology and Center for Genomics and Systems Biology, New York University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Matthew V Rockman

    Department of Biology and Center for Genomics and Systems Biology, New York University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Jonathan Flint, Wellcome Trust Centre for Human Genetics, United Kingdom

Publication history

  1. Received: June 3, 2015
  2. Accepted: August 21, 2015
  3. Accepted Manuscript published: August 22, 2015 (version 1)
  4. Version of Record published: September 15, 2015 (version 2)
  5. Version of Record updated: March 24, 2016 (version 3)

Copyright

© 2015, Paaby 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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