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Multicopy suppression underpins metabolic evolvability.

Wayne M Patrick1, Erik M Quandt, Dan B Swartzlander

  • 1Department of Biochemistry, Center for Fundamental and Applied Molecular Evolution, Emory University, Atlanta, Georgia, USA.

Molecular Biology and Evolution
|September 22, 2007
PubMed
Summary
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Multifunctional genes are common in Escherichia coli, with 20% of gene knockouts rescued by overexpressing other genes. This suggests enzyme promiscuity, or the ability to perform secondary functions, is a key mechanism for metabolic adaptation and evolution.

Area of Science:

  • Genomics
  • Biochemistry
  • Evolutionary Biology

Background:

  • Understanding the origin of new metabolic functions relies on limited genetic and biochemical evidence.
  • Enzyme promiscuity (catalyzing different reactions) and substrate ambiguity (catalyzing the same reaction on different substrates) are known mechanisms for adaptation.
  • The prevalence and chemical nature of these secondary enzymatic activities have not been systematically studied.

Purpose of the Study:

  • To systematically identify multifunctional genes in the Escherichia coli genome.
  • To investigate the frequency and diversity of enzyme promiscuity as a source of metabolic robustness and evolvability.

Main Methods:

  • Screened 104 single-gene knockout strains of Escherichia coli.
  • Assessed rescue of auxotrophy by overexpressing noncognate genes.

Related Experiment Videos

  • Analyzed the relationship between deleted genes and their suppressors.

    • Main Results:

    • 20% of auxotrophic knockout strains were rescued by overexpressing a different, noncognate gene.
    • The rescuing gene was typically unrelated to the deleted gene, indicating promiscuity arises from contingency.
    • Demonstrated a wide range of mechanistic diversity in gene function.

    Conclusions:

    • Multifunctional genes are prevalent in the Escherichia coli genome.
    • Enzyme promiscuity is a common and significant factor in metabolic robustness and evolvability.
    • This study provides a genome-wide perspective on the adaptive potential of gene multifunctionality.