Molecular evolution and functional divergence of alcohol dehydrogenases in animals, fungi and plants

Abstract

Alcohol dehydrogenases belong to the large superfamily of medium-chain dehydrogenases/reductases, which occur throughout the biological world and are involved with many important metabolic routes. We considered the phylogeny of 190 ADH sequences of animals, fungi, and plants. Non-class III Caenorhabditis elegans ADHs were seen closely related to tetrameric fungal ADHs. ADH3 forms a sister group to amphibian, reptilian, avian and mammalian non-class III ADHs. In fishes, two main forms are identified: ADH1 and ADH3, whereas in amphibians there is a new ADH form (ADH8). ADH2 is found in Mammalia and Aves, and they formed a monophyletic group. Additionally, mammalian ADH4 seems to result from an ADH1 duplication, while in Fungi, ADH formed clusters based on types and genera. The plant ADH isoforms constitute a basal clade in relation to ADHs from animals. We identified amino acid residues responsible for functional divergence between ADH types in fungi, mammals, and fishes. In mammals, these differences occur mainly between ADH1/ADH4 and ADH3/ADH5, whereas functional divergence occurred in fungi between ADH1/ADH5, ADH5/ADH4, and ADH5/ADH3. In fishes, the forms also seem to be functionally divergent. The ADH family expansion exemplifies a neofunctionalization process where reiterative duplication events are related to new activities.

Variation in protein coding genes identifies information flow as a contributor to animal complexity

“…1A) indicated that the oxidation of alcohol, mRNA processing, notably splicing, aspects of DNA repair and protein transport via vesicles should also be considered. For the oxidation of alcohol, the main component of functional diversity is the reiterative gene duplication followed by sub- and neo-functionalization that have produced a range of enzymes that metabolize ethanol and related alcohols 33 34 . Analysis of interactions amongst the Compx ortho-sets via STRING identified components of the spliceosome and of vesicular transport and in addition highlights chromatin remodeling and the Mediator complex, consistent with the results from the previous, more limited, survey 14 .…”

An Ancient Mutation in the TPH1 Gene is Consistent with the Changes in Mammalian Reproductive Rhythm

“…The selection pressure of genes was indicated by the ratio ( ω ) of non-synonymous substitution and synonymous substitution number ( d N / d S ). When ω = 1, the gene is neutrally selected; when ω < 1, the gene is purified; when ω > 1, the gene is positively selected [45].…”

“…Q (k) is the site ( k )-specific score corresponding to the posterior probability that site k is related to type-I functional divergence. Based on Thompson and his colleagues’ report, 0.9 was chosen as the critical value of Q (k) , and the site of Q (k) > 0.9 was regarded as an important amino acid leading to functional divergence [45].…”

Alcohol Dehydrogenases as Catalysts in Organic Synthesis

“…ADHs are ubiquitous in all three domains of life-Archea, Bacteria and Eukarya (Machielsen et al, 2006;Gaona-López et al, 2016;Thompson et al, 2018). In the early days of biocatalysis, naturally available enzymes have been used; the ADH from horse liver (HLADH) (Batelli and Stern, 1910;Lutwak-Mann, 1938) or the ADH from yeast (YADH) (de Smidt et al, 2008) being some prominent examples.…”