1. Evolutionary Biology
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Ongoing resolution of duplicate gene functions shapes the diversification of a metabolic network

  1. Meihua Christina Kuang
  2. Paul D Hutchins
  3. Jason D Russell
  4. Joshua J Coon
  5. Chris Todd Hittinger  Is a corresponding author
  1. University of Wisconsin-Madison, United States
Research Article
  • Cited 14
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Cite this article as: eLife 2016;5:e19027 doi: 10.7554/eLife.19027

Abstract

The evolutionary mechanisms leading to duplicate gene retention are well understood, but the long-term impacts of paralog differentiation on the regulation of metabolism remain underappreciated. Here we experimentally dissect the functions of two pairs of ancient paralogs of the GALactose sugar utilization network in two yeast species. We show that the Saccharomyces uvarum network is more active, even as over-induction is prevented by a second co-repressor that the model yeast Saccharomyces cerevisiae lacks. Surprisingly, removal of this repression system leads to a strong growth arrest, likely due to overly rapid galactose catabolism and metabolic overload. Alternative sugars, such as fructose, circumvent metabolic control systems and exacerbate this phenotype. We further show that S. cerevisiae experiences homologous metabolic constraints that are subtler due to how the paralogs have diversified. These results show how the functional differentiation of paralogs continues to shape regulatory network architectures and metabolic strategies long after initial preservation.

Data availability

The following data sets were generated
    1. Kuang MC
    2. Hittinger T
    (2016) RNA-Seq of Saccharomyces uvarum
    Publicly available at the NCBI Short Read Archive (accession no: SRP077015).

Article and author information

Author details

  1. Meihua Christina Kuang

    Laboratory of Genetics, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3206-6525
  2. Paul D Hutchins

    Genome Center of Wisconsin, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Jason D Russell

    Genome Center of Wisconsin, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Joshua J Coon

    Genome Center of Wisconsin, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Chris Todd Hittinger

    Laboratory of Genetics, University of Wisconsin-Madison, Madison, United States
    For correspondence
    cthittinger@wisc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5088-7461

Funding

National Science Foundation (DEB-1253634 , DEB-1442148)

  • Chris Todd Hittinger

National Institute of Food and Agriculture (Hatch Project 1003258)

  • Chris Todd Hittinger

DOE Great Lakes Bioenergy Research Center (DOE Office of Science BER DE-FC02-07ER64494)

  • Joshua J Coon
  • Chris Todd Hittinger

Pew Charitable Trusts (Pew Scholar in the Biomedical Sciences)

  • Chris Todd Hittinger

Alexander von Humboldt-Stiftung (Alfred Toepfer Faculty Fellow)

  • Chris Todd Hittinger

National Institutes of Health (R35 GM118110)

  • Joshua J Coon

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

Reviewing Editor

  1. Leonid Kruglyak, Howard Hughes Medical Institute, Uuniversity of California, Los Angeles, United States

Publication history

  1. Received: June 21, 2016
  2. Accepted: September 28, 2016
  3. Accepted Manuscript published: September 30, 2016 (version 1)
  4. Accepted Manuscript updated: October 5, 2016 (version 2)
  5. Version of Record published: November 1, 2016 (version 3)

Copyright

© 2016, Kuang 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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Further reading

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    Many primate genes produce circular RNAs (circRNAs). However, the extent of circRNA conservation between closely related species remains unclear. By comparing tissue-specific transcriptomes across over 70 million years of primate evolution, we identify that within 3 million years circRNA expression profiles diverged such that they are more related to species identity than organ type. However, our analysis also revealed a subset of circRNAs with conserved neural expression across tens of millions of years of evolution. By comparing to species-specific circRNAs, we identified that the downstream intron of the conserved circRNAs display a dramatic lengthening during evolution due to the insertion of novel retrotransposons. Our work provides comparative analyses of the mechanisms promoting circRNAs to generate increased transcriptomic complexity in primates.

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    Franziska Gruhl et al.
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    Circular RNAs (circRNAs) are found across eukaryotes and can function in post-transcriptional gene regulation. Their biogenesis through a circle-forming backsplicing reaction is facilitated by reverse-complementary repetitive sequences promoting pre-mRNA folding. Orthologous genes from which circRNAs arise, overall contain more strongly conserved splice sites and exons than other genes, yet it remains unclear to what extent this conservation reflects purifying selection acting on the circRNAs themselves. Our analyses of circRNA repertoires from five species representing three mammalian lineages (marsupials, eutherians: rodents, primates) reveal that surprisingly few circRNAs arise from orthologous exonic loci across all species. Even the circRNAs from orthologous loci are associated with young, recently active and species-specific transposable elements, rather than with common, ancient transposon integration events. These observations suggest that many circRNAs emerged convergently during evolution - as a byproduct of splicing in orthologs prone to transposon insertion. Overall, our findings argue against widespread functional circRNA conservation.