Resurrecting ancestral alcohol dehydrogenases from yeast
Open accessAbstract
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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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].”
From Adaptive laboratory evolution—Principles and applications for biotechnology (2013) · cites this paper as [153]
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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
- PMC
- PMC3618678
- 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
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- 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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