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狒狒肝脏乙醇脱氢酶编码cDNA的克隆与测序:与人类乙醇脱氢酶β亚基拥有共同祖先谱系及灵长类辐射前I类乙醇脱氢酶基因重复的证据

Cloning and sequencing of cDNA encoding baboon liver alcohol dehydrogenase: evidence for a common ancestral lineage with the human alcohol dehydrogenase beta subunit and for class I ADH gene duplications predating primate radiation.

作者信息

Trezise A E, Godfrey E A, Holmes R S, Beacham I R

机构信息

Division of Science and Technology, Griffith University, Nathan, Brisbane, Australia.

出版信息

Proc Natl Acad Sci U S A. 1989 Jul;86(14):5454-8. doi: 10.1073/pnas.86.14.5454.

DOI:10.1073/pnas.86.14.5454
PMID:2748595
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC297641/
Abstract

The baboon has at least five alcohol dehydrogenases (ADH; alcohol:NAD+ oxidoreductase, EC 1.1.1.1) and has distinct liver and kidney class I isozymes. A rat liver class I ADH partial cDNA was used to screen a baboon liver cDNA library. A cDNA clone was isolated and sequenced and found to contain the entire coding region for baboon liver ADH, 12 nucleotides of the 5' noncoding region, and 256 nucleotides of the 3' noncoding region. The amino acid sequence deduced from this cDNA most closely resembles that of human liver ADH beta subunit (ADH-beta): 363 of 374 residues were identical. This suggested that baboon liver class I ADH is of the same ancestral lineage as the human ADH-beta. In contrast to human liver, only a single ADH-beta transcript is observed in baboon liver. A comparison of human and baboon ADH 3' noncoding regions suggests that a single nucleotide change in a polyadenylylation signal consensus sequence may, in part, be responsible for the generation of ADH-beta transcripts with variable-length 3' ends in human liver. A nucleotide substitution rate of 0.5 x 10(-9) substitutions per site per year for primate class I ADH genes was deduced from the data, which suggests that the alpha-beta gamma separation of human ADH genes occurred about 60 million years ago, and that primate class I ADH gene duplications predated primate radiation.

摘要

狒狒至少有五种乙醇脱氢酶(ADH;乙醇:NAD+氧化还原酶,EC 1.1.1.1),并且具有不同的肝脏和肾脏I类同工酶。用大鼠肝脏I类ADH部分cDNA筛选狒狒肝脏cDNA文库。分离并测序了一个cDNA克隆,发现它包含狒狒肝脏ADH的完整编码区、5'非编码区的12个核苷酸和3'非编码区的256个核苷酸。从该cDNA推导的氨基酸序列与人类肝脏ADHβ亚基(ADH-β)的氨基酸序列最为相似:374个残基中有363个相同。这表明狒狒肝脏I类ADH与人类ADH-β具有相同的祖先谱系。与人类肝脏不同,在狒狒肝脏中仅观察到单一的ADH-β转录本。人类和狒狒ADH 3'非编码区的比较表明,聚腺苷酸化信号共有序列中的单个核苷酸变化可能部分导致了人类肝脏中具有可变长度3'末端的ADH-β转录本的产生。从这些数据推断,灵长类I类ADH基因的核苷酸替换率为每年每个位点0.5×10^(-9)次替换,这表明人类ADH基因的α-β-γ分离发生在约6000万年前,并且灵长类I类ADH基因的复制早于灵长类动物的辐射。

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