Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés, Unité Mixte de Recherche-Centre National de la Recherche Scientifique 5504, Institut National des Sciences Appliquées de Toulouse, 31077 Toulouse Cedex 4, France.
Genetics. 2010 Jun;185(2):395-404. doi: 10.1534/genetics.110.118190.
Molecular biologists have long searched for molecular mechanisms responsible for tuning the rate of genetic-variant generation (RGVG) in fluctuating environments. In spite of several bacterial examples, no regulated variation in the RGVG has been identified in eukaryotic systems. Based notably on the example of industrial and pathogenic yeasts, this article proposes a nonregulated molecular evolutionary mechanism for the appearance of the transient increase of the RGVG in eukaryotic cell populations facing challenging environments. The stochastic nature of gene expression allows a model in which the RGVG in the population can be rapidly tuned as a result of a simple Darwinian process acting on noise-driven heterogeneity in the RGVG from cell to cell. The high flexibility conferred through this model could resolve paradoxical situations, especially concerning the mutator phenotype in cancer cells.
分子生物学家长期以来一直在寻找导致遗传变异产生率（RGVG）在波动环境中发生变化的分子机制。尽管有几个细菌的例子，但在真核系统中尚未发现 RGVG 的调节变化。本文主要以工业和致病性酵母为例，提出了一种非调控的分子进化机制，用于解释真核细胞群体在面临挑战性环境时，RGVG 短暂增加的现象。基因表达的随机性使得这样一种模型成为可能，即由于简单的达尔文过程作用于细胞间 RGVG 的噪声驱动异质性，种群中的 RGVG 可以迅速调整。通过这种模型赋予的高灵活性可以解决矛盾的情况，特别是涉及癌细胞中的突变表型。
