Department of Biological Sciences, California State University, Sacramento, CA 95819-6077, USA.
Department of Mathematics and Statistics, California State University, Sacramento, CA 95819-6051, USA.
G3 (Bethesda). 2023 Mar 9;13(3). doi: 10.1093/g3journal/jkac327.
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.
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，在这些环境中，由于未适应细胞的生长限制所导致的压力，它们会得到富集。我们使用三种独立的 Acinetobacter baylyi 模型系统检测了这一理论，这些系统专门选择 cat 基因扩增突变体。我们的结果表明，所有 cat 基因扩增突变体菌落都是通过多步过程产生的。虽然晚期步骤发生在选择暴露期间，但这些突变体源自于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次次要步骤，在数天到数周内产生更高的扩增，最终形成可见的高拷贝扩增菌落。基于这些发现，该 Acinetobacter 系统中的扩增可以通过不需要应激反应的自然选择过程来解释。这些发现对理解生长限制选择性环境在癌症发展中的作用具有重要意义。我们建议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，以便在获得高拷贝扩增之前，促进早期癌症的检测和治疗。
