Cited by 341Fungal and yeast genetics researchEvolution and Genetic DynamicsGenomics and Phylogenetic Studies

Resurrecting ancestral alcohol dehydrogenases from yeast

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Thomson, J Michael, Gaucher, Eric A, Burgan, Michelle F, De Kee, Danny W, Li, Tang, Aris, John P, Benner, Steven A·2005·Nature Genetics

Abstract

Modern yeast living in fleshy fruits rapidly convert sugars into bulk ethanol through pyruvate. Pyruvate loses carbon dioxide to produce acetaldehyde, which is reduced by alcohol dehydrogenase 1 (Adh1) to ethanol, which accumulates. Yeast later consumes the accumulated ethanol, exploiting Adh2, an Adh1 homolog differing by 24 (of 348) amino acids. As many microorganisms cannot grow in ethanol, accumulated ethanol may help yeast defend resources in the fruit. We report here the resurrection of the last common ancestor of Adh1 and Adh2, called Adh(A). The kinetic behavior of Adh(A) suggests that the ancestor was optimized to make (not consume) ethanol. This is consistent with the hypothesis that before the Adh1-Adh2 duplication, yeast did not accumulate ethanol for later consumption but rather used Adh(A) to recycle NADH generated in the glycolytic pathway. Silent nucleotide dating suggests that the Adh1-Adh2 duplication occurred near the time of duplication of several other proteins involved in the accumulation of ethanol, possibly in the Cretaceous age when fleshy fruits arose. These results help to connect the chemical behavior of these enzymes through systems analysis to a time of global ecosystem change, a small but useful step towards a planetary systems biology.

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Crossref · 10.1038/ng1553

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  • Duplications and large scale genomic variations, although they can lead to significant issues such as genomic instability, play a major role in yeast evolution.

    “As such, ALE studies highlight that duplications and large scale genomic variations, although they can lead to significant issues such as genomic instability [152], play a major role in e.g. yeast evolution; this is also indicated by data on wine yeasts, galactose utilization, comparative genomics and drug resistance [115,153-156].”

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Authors
Thomson, J. M., Gaucher, E. A., Burgan, M. F., De Kee, D. W., Li, T., Aris, J. P., & Benner, S. A.
Affiliations
  • University of North Carolina at Chapel Hill (US)
  • Foundation for Applied Molecular Evolution (US)
  • University of Florida (US)
Corresponding author
Benner, Steven A
Venue
Nature Genetics
Published
2005-05-01
Volume
37
Issue
6
Pages
630-635
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
OpenAlex
W1998447705
Cited by
341
References
30
Citations by year
2026: 8 · 2025: 8 · 2024: 14 · 2023: 22 · 2022: 16 · 2021: 10 · 2020: 13 · 2019: 24 · 2018: 17 · 2017: 17 · 2016: 15 · 2015: 19 · 2014: 21 · 2013: 20 · 2012: 19
FWCI
4.52
Type
journal article
Language
en
Open access
Locations
  • Nature Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Aeronautics and Space Administration
  • National Institute on Aging (R21AG023719)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
Keywords
ancestral protein reconstruction, alcohol dehydrogenase, ADH1, ADH2, Saccharomyces cerevisiae, gene duplication, ethanol accumulation, fleshy fruits, NADH regeneration, enzyme kinetics, Cretaceous
MeSH terms
Alcohol Dehydrogenase, Ethanol, Base Sequence, Biological Evolution, Molecular Sequence Data, Saccharomyces cerevisiae

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