Compensatory mutations, antibiotic resistance and the population genetics of adaptive evolution in bacteria.
Compensatory mutations, antibiotic resistance and the population genetics of adaptive evolution in bacteria.
复制标题
细菌的补偿性突变、抗生素耐药性和适应性进化的群体遗传学。
DOI：
10.1093/genetics/154.3.985
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发表时间：
2000
期刊：
影响因子：
3.3
通讯作者：
Walker,N
中科院分区：
文献类型：
--
作者：
Levin,BR;Perrot,V;Walker,N
在没有选择药物的情况下，对抗生素和其他化疗药物产生耐药性的染色体突变通常会使微生物的适应性付出代价。最近对大肠杆菌、艾滋病毒和鼠伤寒沙门氏菌适应这些“耐药性成本”的体内和体外实验研究发现，在缺乏这些药物的情况下，进化通常会导致改善这些成本的突变增加，而不是更高适应度、对药物敏感的逆转录物。为了确定这种代偿性进化而不是逆转发生的条件，我们对大肠杆菌的低适应度rpsL（链霉素抗性）突变进行了计算机模拟、体外实验和DNA测序研究，这些突变有和没有补偿这些核糖体蛋白突变的适应度成本的突变。我们的研究结果支持这样的假设，即在这些实验中，中等适应度补偿突变体的上升，而不是高适应度逆转突变体的上升，可以归因于相对于逆转的更高的补偿性突变率，以及与序列传代相关的数值瓶颈。我们认为这些瓶颈是寄生和共生微生物种群动态所固有的，并讨论了这些结果对寄生和共生微生物耐药性和适应性进化问题的影响。
In the absence of the selecting drugs, chromosomal mutations for resistance to antibiotics and other chemotheraputic agents commonly engender a cost in the fitness of microorganisms. Recent in vivo and in vitro experimental studies of the adaptation to these “costs of resistance” in Escherichia coli, HIV, and Salmonella typhimurium found that evolution in the absence of these drugs commonly results in the ascent of mutations that ameliorate these costs, rather than higher-fitness, drug-sensitive revertants. To ascertain the conditions under which this compensatory evolution, rather than reversion, will occur, we did computer simulations, in vitro experiments, and DNA sequencing studies with low-fitness rpsL (streptomycin-resistant) mutants of E. coli with and without mutations that compensate for the fitness costs of these ribosomal protein mutations. The results of our investigation support the hypothesis that in these experiments, the ascent of intermediate-fitness compensatory mutants, rather than high-fitness revertants, can be attributed to higher rates of compensatory mutations relative to that of reversion and to the numerical bottlenecks associated with serial passage. We argue that these bottlenecks are intrinsic to the population dynamics of parasitic and commensal microbes and discuss the implications of these results to the problem of drug resistance and adaptive evolution in parasitic and commmensal microorganisms in general.
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影响因子：
1.8
作者：
Ameen，Edrees
通讯作者：
Ameen，Edrees
DOI：
10.1073/pnas.95.7.3949
发表时间：
1998-03-31
影响因子：
11.1
作者：
Björkman, J;Hughes, D;Andersson, DI
通讯作者：
Andersson, DI
影响因子：
15.9
作者：
Levin, Bruce R.;Bull, James J.
通讯作者：
Bull, James J.
影响因子：
5.6
作者：
ROSSET, R;GORINI, L
通讯作者：
GORINI, L