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Resurrecting ancestral alcohol dehydrogenases from yeast

Nature Genetics volume 37, pages 630–635 (2005)Cite this article

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 fruit1. We report here the resurrection of the last common ancestor2 of Adh1 and Adh2, called AdhA. The kinetic behavior of AdhA 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 AdhA 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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Figure 1: The pathway by which yeast make, accumulate and then consume ethanol.
Figure 2: Maximum likelihood trees interrelating sequences determined in this work with sequences in the publicly available database.

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Acknowledgements

We thank A. Falcon and T. Barnash for their assistance. Funding was provided by the US National Research Council, the US National Aeronautics and Space Administration's Astrobiology Institute (E.A.G.) and the US National Aeronautics and Space Administration Exobiology program (S.A.B.).

Author information

Author notes

  1. J Michael Thomson

    Present address: Department of Cell & Developmental Biology, University of North Carolina, Chapel Hill, North Carolina, 27599, USA

  2. Michelle F Burgan

    Present address: Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina, 27710, USA

Authors and Affiliations

  1. Department of Anatomy and Cell Biology, University of Florida, Gainesville, 32610, Florida, USA

    J Michael Thomson, John P Aris & Steven A Benner

  2. Foundation for Applied Molecular Evolution, Gainesville, 32601, Florida, USA

    Eric A Gaucher, Danny W De Kee & Tang Li

  3. Department of Chemistry, University of Florida, Gainesville, 32611, Florida, USA

    Michelle F Burgan & Steven A Benner

  4. Department of Cell & Developmental Biology, University of North Carolina, Chapel Hill, North Carolina, 27599, USA

    Michelle F Burgan

  5. Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina, 27710, USA

    J Michael Thomson

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  1. J Michael Thomson
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Correspondence to Steven A Benner.

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Supplementary information

Supplementary Fig. 1

Complementation of Adh 1/2 double minus with ancestral proteins. (PDF 4843 kb)

Supplementary Fig. 2

Trees showing f2 values for families with more than two paralogs. (PDF 87 kb)

Supplementary Table 1

Newly cloned and existing ADH genes used in the ancestral reconstruction. (PDF 163 kb)

Supplementary Note (PDF 130 kb)

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Thomson, J., Gaucher, E., Burgan, M. et al. Resurrecting ancestral alcohol dehydrogenases from yeast. Nat Genet 37, 630–635 (2005). https://doi.org/10.1038/ng1553

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