Multiple-stress analysis for isolation of Drosophila longevity genes
Multiple-stress analysis for isolation of Drosophila longevity genes
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DOI：
10.1073/pnas.0404648101
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发表时间：
2004-08-24
影响因子：
11.1
通讯作者：
Benzer, S
中科院分区：
文献类型：
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作者：
Wang, HD;Kazemi-Esfarjani, P;Benzer, S
寿命长的生物体往往对各种形式的环境压力更具抵抗力。果蝇长寿突变体玛士撒拉就是一个例子，它对热、氧化剂和饥饿的抵抗力增强。为了鉴定受这三种应激调控的基因，我们通过从“应激”cDNA中减去“非应激”cDNA，为每一种构建了cDNA文库，并使用DNA杂交来鉴定受所有三种应激调控的基因。这项筛选确实确定了13个基因，其中一些已知与长寿有关，还有候选基因。选择其中的两个，hsp 26和hsp 27，通过产生转基因系和通过使用上游激活序列/GAL 4系统来测试它们对寿命的影响。hsp 26或hsp 27的过度表达延长了30%的平均寿命，果蝇也表现出更强的抗应激能力。结果表明，多重胁迫筛选可用于鉴定新的长寿基因。
Long-lived organisms tend to be more resistant to various forms of environmental stress. An example is the Drosophila longevity mutant, methuselah, which has enhanced resistance to heat, oxidants, and starvation. To identify genes regulated by these three stresses, we made a cDNA library for each by subtraction of "unstressed" from "stressed" cDNA and used DNA hybridization to identify genes that are regulated by all three. This screen indeed identified 13 genes, some already known to be involved in longevity, plus candidate genes. Two of these, hsp26 and hsp27, were chosen to test for their effects on lifespan by generating transgenic lines and by using the upstream activating sequence/GAL4 system. Overexpression of either hsp26 or hsp27 extended the mean lifespan by 30%, and the flies also displayed increased stress resistance. The results demonstrate that multiple-stress screening can be used to identify new longevity genes.