Park Annie, Ghezzi Alfredo, Wijesekera Thilini P, Atkinson Nigel S
Department of Neuroscience and The Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, TX, United States.
Department of Biology, University of Puerto Rico, Rio Piedras. San Juan, PR, United States.
Neuropharmacology. 2017 Aug 1;122:22-35. doi: 10.1016/j.neuropharm.2017.01.032. Epub 2017 Feb 1.
Drosophila melanogaster has become a significant model organism for alcohol research. In flies, a rich variety of behaviors can be leveraged for identifying genes affecting alcohol responses and adaptations. Furthermore, almost all genes can be easily genetically manipulated. Despite the great evolutionary distance between flies and mammals, many of the same genes have been implicated in strikingly similar alcohol-induced behaviors. A major problem in medical research today is that it is difficult to extrapolate from any single model system to humans. Strong evolutionary conservation of a mechanistic response between distantly related organisms, such as flies and mammals, is a powerful predictor that conservation will continue all the way to humans. This review describes the state of the Drosophila alcohol research field. It describes common alcohol behavioral assays, the independent origins of resistance and tolerance, the results of classical genetic screens and candidate gene analysis, and the outcomes of recent genomics studies employing GWAS, transcriptome, miRNA, and genome-wide histone acetylation surveys. This article is part of the Special Issue entitled "Alcoholism".
黑腹果蝇已成为酒精研究的重要模式生物。在果蝇中,可以利用丰富多样的行为来鉴定影响酒精反应和适应性的基因。此外,几乎所有基因都能轻松地进行遗传操作。尽管果蝇与哺乳动物在进化上相距甚远,但许多相同的基因都与惊人相似的酒精诱导行为有关。当今医学研究中的一个主要问题是,很难从任何单一模型系统推断到人类。在果蝇和哺乳动物等远缘生物之间,机械反应具有很强的进化保守性,这有力地预示着这种保守性将一直延续到人类。这篇综述描述了果蝇酒精研究领域的现状。它介绍了常见的酒精行为检测方法、抗性和耐受性的独立起源、经典遗传筛选和候选基因分析的结果,以及最近采用全基因组关联研究(GWAS)、转录组学、微小RNA(miRNA)和全基因组组蛋白乙酰化调查的基因组学研究成果。本文是名为“酒精中毒”的特刊的一部分。