Multiple pathways of selected gene amplification during adaptive mutation
Multiple pathways of selected gene amplification during adaptive mutation
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DOI：
10.1073/pnas.0608309103
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发表时间：
2006-11-14
影响因子：
11.1
通讯作者：
Roth, John R.
中科院分区：
文献类型：
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作者：
Kugelberg, Elisabeth;Kofoid, Eric;Roth, John R.
在一种被称为“适应性突变”的现象中，一群具有lac操纵子(lac-)突变的细菌细胞在长期暴露于选择性生长条件(乳糖)中积累lac(+)逆转株。有证据表明，选择性条件不会增加突变率，反而有利于具有泄漏的lac等位基因重复的稀有细胞的生长。拷贝数(扩增)的进一步增加改善了生长，并通过向克隆增加更多的突变靶标(细胞和每个细胞的乳胶拷贝)增加了序列改变的可能性。这里描述了这些复制和放大。在选择之前，具有大(134-kb)lac重复和长连接序列(>；1kb)的细胞很常见(0.2%)。在低拷贝数lac扩增的细胞中选择后，发现了相同的大重复序列。令人惊讶的是，在高拷贝数扩增中发现了较小的重复(平均34kb)。当缺失修改先前存在的大重复复制时，形成小重复复制。较短的重复长度允许较高的乳糖扩增和较好的乳糖生长。因此，选择有利于一系列的基因扩增类型，这些类型通过增加靶点来使序列改变的可能性更大。这些发现与任何生物系统中的遗传适应有关，在这些生物系统中，可以通过增加基因拷贝来增加适应性(例如，癌症和细菌耐药性)。
in a phenomenon referred to as "adaptive mutation," a population of bacterial cells with a mutation in the lac operon (lac-) accumulates Lac(+) revertants during prolonged exposure to selective growth conditions (lactose). Evidence was provided that selective conditions do not increase the mutation rate but instead favor the growth of rare cells with a duplication of the leaky lac allele. A further increase in copy number (amplification) improves growth and increases the likelihood of a sequence change by adding more mutational targets to the clone (cells and lac copies per cell). These duplications and amplifications are described here. Before selection, cells with large (134-kb) lac duplications and long junction sequences (> 1 kb) were common (0.2%). The same large repeats were found after selection in cells with a low-copy-number lac amplification. Surprisingly, smaller repeats (average, 34 kb) were found in high-copy-number amplifications. The small-repeat duplications form when deletions modify a preexisting large-repeat duplication. The shorter repeat size allowed higher lac amplification and better growth on lactose. Thus, selection favors a succession of gene-amplification types that make sequence changes more probable by adding targets. These findings are relevant to genetic adaptation in any biological systems in which fitness can be increased by adding gene copies (e.g., cancer and bacterial drug resistance).