Evolution of Yin and Yang isoforms of a chromatin remodeling subunit precedes the creation of two genes

  1. Wen Xu
  2. Lijiang Long
  3. Yuehui Zhao
  4. Lewis Stevens
  5. Irene Felipe
  6. Javier Munoz
  7. Ronald E Ellis
  8. Patrick T McGrath  Is a corresponding author
  1. Georgia Institute of Technology, United States
  2. University of Edinburgh, United Kingdom
  3. Spanish National Research Center - CNIO, Spain
  4. Rowan University School of Medicine, United States

Abstract

Genes can encode multiple isoforms, broadening their functions and providing a molecular substrate to evolve phenotypic diversity. Evolution of isoform function is a potential route to adapt to new environments. Here we show that de novo, beneficial alleles in the nurf-1 gene became fixed in two laboratory lineages of C. elegans after isolation from the wild in 1951, before methods of cryopreservation were developed. nurf-1 encodes an ortholog of BPTF, a large (>300kD) multidomain subunit of the NURF chromatin remodeling complex. Using CRISPR-Cas9 genome editing and transgenic rescue, we demonstrate that in C. elegans, nurf-1 has split into two, largely non-overlapping isoforms (NURF-1.D and NURF-1.B, which we call Yin and Yang, respectively) that share only two of 26 exons. Both isoforms are essential for normal gametogenesis but have opposite effects on male/female gamete differentiation. Reproduction in hermaphrodites, which involves production of both sperm and oocytes, requires a balance of these opposing Yin and Yang isoforms. Transgenic rescue and genetic position of the fixed mutations suggest that different isoforms are modified in each laboratory strain. In a related clade of Caenorhabditis nematodes, the shared exons have duplicated, resulting in the split of the Yin and Yang isoforms into separate genes, each containing approximately 200 amino acids of duplicated sequence that has undergone accelerated protein evolution following the duplication. Associated with this duplication event is the loss of two additional nurf-1 transcripts, including the long-form transcript and a newly identified, highly expressed transcript encoded by the duplicated exons. We propose these lost transcripts are non-functional side products necessary to transcribe the Yin and Yang transcripts in the same cells. Our work demonstrates how gene sharing, through the production of multiple isoforms, can precede the creation of new, independent genes.

Data availability

Sequencing reads were uploaded to the SRA under PRJNA526473

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Wen Xu

    School of Biological Sciences, Georgia Institute of Technology, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2085-7223
  2. Lijiang Long

    School of Biological Sciences, Georgia Institute of Technology, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Yuehui Zhao

    School of Biological Sciences, Georgia Institute of Technology, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9496-0023
  4. Lewis Stevens

    Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6075-8273
  5. Irene Felipe

    Epethelial Carcinogenesis Group, Spanish National Research Center - CNIO, Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  6. Javier Munoz

    Proteomics Unit - ProteoRed-ISCIII, Spanish National Research Center - CNIO, Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  7. Ronald E Ellis

    Department of Molecular Biology, Rowan University School of Medicine, Stratford, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Patrick T McGrath

    School of Biological Sciences, Georgia Institute of Technology, Atlanta, United States
    For correspondence
    patrick.mcgrath@biology.gatech.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1598-3746

Funding

National Institute of General Medical Sciences (R01GM114170)

  • Patrick T McGrath

National Institute of General Medical Sciences (R01GM121688)

  • Ronald E Ellis

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

Reviewing Editor

  1. Erich M Schwarz, Cornell University, United States

Version history

  1. Received: May 1, 2019
  2. Accepted: September 5, 2019
  3. Accepted Manuscript published: September 9, 2019 (version 1)
  4. Version of Record published: September 19, 2019 (version 2)

Copyright

© 2019, Xu 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. Wen Xu
  2. Lijiang Long
  3. Yuehui Zhao
  4. Lewis Stevens
  5. Irene Felipe
  6. Javier Munoz
  7. Ronald E Ellis
  8. Patrick T McGrath
(2019)
Evolution of Yin and Yang isoforms of a chromatin remodeling subunit precedes the creation of two genes
eLife 8:e48119.
https://doi.org/10.7554/eLife.48119

Share this article

https://doi.org/10.7554/eLife.48119

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