Gene amplification mutations originate prior to selective stress in Acinetobacter baylyi.
Gene amplification mutations originate prior to selective stress in Acinetobacter baylyi.
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DOI：
10.1093/g3journal/jkac327
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发表时间：
2023-03-09
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有争议的适应性扩增理论认为，基因扩增突变是由选择性环境诱导的，在选择性环境中，基因扩增突变由于生长限制对不适应细胞造成的压力而富集。我们测试了这一理论与三个独立的测定使用不动杆菌baylyi模型系统，专门选择猫基因扩增突变体。我们的研究结果表明，所有的猫基因扩增突变体菌落出现通过一个多步骤的过程。虽然后期步骤发生在选择暴露期间，但这些突变体源自在施加生长抑制选择之前形成的低水平扩增突变细胞。在选择过程中，这些部分突变体经历多个二级步骤，在数天至数周内产生更高的扩增，最终形成可见的高拷贝扩增集落。基于这些发现，在这个不动杆菌系统的扩增可以解释为一个自然选择过程，不需要一个压力反应。这些发现对于理解生长限制性选择性环境对癌症发展的作用具有根本意义。我们认为，在高拷贝扩增之前，包含生长因子基因的重复突变可以作为新的基因组生物标志物，以促进早期癌症检测和治疗。
The controversial theory of adaptive amplification states gene amplification mutations are induced by selective environments where they are enriched due to the stress caused by growth restriction on unadapted cells. We tested this theory with three independent assays using an Acinetobacter baylyi model system that exclusively selects for cat gene amplification mutants. Our results demonstrate all cat gene amplification mutant colonies arise through a multistep process. While the late steps occur during selection exposure, these mutants derive from low-level amplification mutant cells that form before growth-inhibiting selection is imposed. During selection, these partial mutants undergo multiple secondary steps generating higher amplification over several days to multiple weeks to eventually form visible high-copy amplification colonies. Based on these findings, amplification in this Acinetobacter system can be explained by a natural selection process that does not require a stress response. These findings have fundamental implications to understanding the role of growth-limiting selective environments on cancer development. We suggest duplication mutations encompassing growth factor genes may serve as new genomic biomarkers to facilitate early cancer detection and treatment, before high-copy amplification is attained.
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DOI：
10.1158/1055-9965.epi-13-0135
发表时间：
2013-04
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
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作者：
Caporaso NE
通讯作者：
Caporaso NE
影响因子：
7.2
作者：
Maisnier-Patin, Sophie;Roth, John R.
通讯作者：
Roth, John R.
影响因子：
82.9
作者：
Andor N;Graham TA;Jansen M;Xia LC;Aktipis CA;Petritsch C;Ji HP;Maley CC
通讯作者：
Maley CC
DOI：
10.1073/pnas.1801930115
发表时间：
2018-07-10
影响因子：
11.1
作者：
Konrad, Anke;Flibotte, Stephane;Katju, Vaishali
通讯作者：
Katju, Vaishali
DOI：
10.1007/1-4020-3764-3_12
发表时间：
2005-01-01
期刊：
GENOME INSTABILITY IN CANCER DEVELOPMENT
影响因子：
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作者：
Debatisse, M;Malfoy, B
通讯作者：
Malfoy, B