Thompson Claudia E, Freitas Loreta B, Salzano Francisco M
Departamento de Farmacociências, Unidade de Genômica e Bioinformática Clínica, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil.
Unidade de Biologia Teórica e Computacional, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Genet Mol Biol. 2018;41(1 suppl 1):341-354. doi: 10.1590/1678-4685-GMB-2017-0047.
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.
乙醇脱氢酶属于中链脱氢酶/还原酶的大型超家族，这类酶广泛存在于生物界，并参与许多重要的代谢途径。我们研究了动物、真菌和植物的190个乙醇脱氢酶序列的系统发育。发现秀丽隐杆线虫的非Ⅲ类乙醇脱氢酶与真菌的四聚体乙醇脱氢酶密切相关。乙醇脱氢酶3与两栖动物、爬行动物、鸟类和哺乳动物的非Ⅲ类乙醇脱氢酶形成姐妹群。在鱼类中，鉴定出两种主要形式：乙醇脱氢酶1和乙醇脱氢酶3，而在两栖动物中有一种新的乙醇脱氢酶形式（乙醇脱氢酶8）。乙醇脱氢酶2存在于哺乳动物和鸟类中，它们形成一个单系群。此外，哺乳动物的乙醇脱氢酶4似乎是由乙醇脱氢酶1复制而来，而在真菌中，乙醇脱氢酶根据类型和属形成簇。植物乙醇脱氢酶同工型相对于动物的乙醇脱氢酶构成一个基部进化枝。我们确定了真菌、哺乳动物和鱼类中乙醇脱氢酶类型之间功能差异所涉及的氨基酸残基。在哺乳动物中，这些差异主要发生在乙醇脱氢酶1/乙醇脱氢酶4和乙醇脱氢酶3/乙醇脱氢酶5之间，而在真菌中，功能差异发生在乙醇脱氢酶1/乙醇脱氢酶5、乙醇脱氢酶5/乙醇脱氢酶4和乙醇脱氢酶5/乙醇脱氢酶3之间。在鱼类中，这些形式似乎在功能上也存在差异。乙醇脱氢酶家族的扩张例证了一个新功能化过程，其中反复的复制事件与新的活性相关。
