Torkelson J, Harris R S, Lombardo M J, Nagendran J, Thulin C, Rosenberg S M
Department of Biochemistry, University of Alberta, Edmonton, Canada.
EMBO J. 1997 Jun 2;16(11):3303-11. doi: 10.1093/emboj/16.11.3303.
Stationary-phase mutation in microbes can produce selected ('adaptive') mutants preferentially. In one system, this occurs via a distinct, recombination-dependent mechanism. Two points of controversy have surrounded these adaptive reversions of an Escherichia coli lac mutation. First, are the mutations directed preferentially to the selected gene in a Lamarckian manner? Second, is the adaptive mutation mechanism specific to the F plasmid replicon carrying lac? We report that lac adaptive mutations are associated with hypermutation in unselected genes, in all replicons in the cell. The associated mutations have a similar sequence spectrum to the adaptive reversions. Thus, the adaptive mutagenesis mechanism is not directed to the lac genes, in a Lamarckian manner, nor to the F' replicon carrying lac. Hypermutation was not found in non-revertants exposed to selection. Therefore, the genome-wide hypermutation underlying adaptive mutation occurs in a differentiated subpopulation. The existence of mutable subpopulations in non-growing cells is important in bacterial evolution and could be relevant to the somatic mutations that give rise to cancers in multicellular organisms.
微生物中的稳定期突变可优先产生被选择的（“适应性”）突变体。在一个系统中，这是通过一种独特的、依赖重组的机制发生的。围绕大肠杆菌乳糖（lac）突变的这些适应性回复突变存在两个争议点。第一，这些突变是否以拉马克式的方式优先指向被选择的基因？第二，适应性突变机制是否特定于携带乳糖基因的F质粒复制子？我们报告称，乳糖适应性突变与细胞内所有复制子中未被选择基因的超突变有关。相关突变与适应性回复突变具有相似的序列谱。因此，适应性诱变机制并非以拉马克式的方式指向乳糖基因，也不是指向携带乳糖基因的F'复制子。在接受选择的非回复突变体中未发现超突变。因此，适应性突变背后的全基因组超突变发生在一个分化的亚群体中。非生长细胞中可变亚群体的存在在细菌进化中很重要，并且可能与多细胞生物体中引发癌症的体细胞突变有关。
