Age- and Temperature-Dependent Somatic Mutation Accumulation in Drosophila melanogaster
Age- and Temperature-Dependent Somatic Mutation Accumulation in Drosophila melanogaster
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DOI：
10.1371/journal.pgen.1000950
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发表时间：
2010-05-01
期刊：
影响因子：
4.5
通讯作者：
Vijg, Jan
中科院分区：
文献类型：
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作者：
Garcia, Ana Maria;Calder, R. Brent;Vijg, Jan
我们之前使用含有可从基因组 DNA 中有效恢复的突变报告基因的转基因小鼠模型，证明了突变以组织特异性方式在衰老小鼠中积累。通过在果蝇中应用最近开发的类似的基于报告基因的测定，我们现在发现果蝇体组织中 lacZ 位点的突变频率约为小鼠组织中的三倍，其中大基因组重排的比例要高得多。与小鼠类似，果蝇的体细胞突变也会随着年龄的增长而积累，但在较高的温度下，体细胞突变的积累速度要快得多，这种情况在无脊椎动物中与寿命缩短有关。发现大多数突变在胸部积累，较少在腹部积累，这表明高度氧化的飞行肌可能是基因毒性应激的来源。这些结果表明，寿命较短的果蝇的体细胞突变负荷比寿命较长的小鼠严重得多，果蝇的突变率与生物衰老成正比，而不是与时间衰老成正比。
Using a transgenic mouse model harboring a mutation reporter gene that can be efficiently recovered from genomic DNA, we previously demonstrated that mutations accumulate in aging mice in a tissue-specific manner. Applying a recently developed, similar reporter-based assay in Drosophila melanogaster, we now show that the mutation frequency at the lacZ locus in somatic tissue of flies is about three times as high as in mouse tissues, with a much higher fraction of large genome rearrangements. Similar to mice, somatic mutations in the fly also accumulate as a function of age, but they do so much more quickly at higher temperature, a condition which in invertebrates is associated with decreased life span. Most mutations were found to accumulate in the thorax and less in abdomen, suggesting the highly oxidative flight muscles as a possible source of genotoxic stress. These results show that somatic mutation loads in short-lived flies are much more severe than in the much longer-lived mice, with the mutation rate in flies proportional to biological rather than chronological aging.