Instituto Gulbenkian de Ciência, Oeiras, Portugal.
Mol Biol Evol. 2012 May;29(5):1417-28. doi: 10.1093/molbev/msr302. Epub 2011 Dec 5.
The distribution of effects of beneficial mutations is key to our understanding of biological adaptation. Yet, empirical estimates of this distribution are scarce, and its functional form is largely unknown. Theoretical models of adaptation predict that the functional form of this distribution should depend on the distance to the optimum. Here, we estimate the rate and distribution of adaptive mutations that compensate for the effect of a single deleterious mutation, which causes antibiotic resistance. Using a system with multiple molecular markers, we estimate the distribution of fitness effects of mutations at two distances from the adaptive peak in 60 populations of Escherichia coli. We find that beneficial mutations, which can contribute to compensatory evolution, occur at very high rates, of the order of 10(-5) per genome per generation and can be detected within a few tens of generations. They cause an average fitness increase of 2.5% and 3.6%, depending on the cost of resistance, which is expected under Fisher's geometrical model of adaptation. Moreover, we provide the first description of the distribution of beneficial mutations, segregating during the process of compensatory evolution, to antibiotic resistances bearing different costs. Hence, these results have important implications to understanding the spread and maintenance of antibiotic resistance in bacteria.
有益突变的效应分布是我们理解生物适应的关键。然而，这种分布的经验估计很少，其功能形式在很大程度上是未知的。适应的理论模型预测，这种分布的功能形式应该取决于与最优值的距离。在这里，我们估计了补偿单个有害突变（导致抗生素耐药性）效应的适应性突变的速率和分布。使用具有多个分子标记的系统，我们在大肠杆菌的 60 个种群中，估计了两个距离适应峰的突变的适应度效应分布。我们发现，有益突变（有助于补偿进化）的发生速度非常快，每个基因组每代约为 10(-5)，并且可以在几十代内检测到。它们导致平均适应度增加 2.5%和 3.6%，这取决于耐药性的成本，这在适应的费希尔几何模型下是可以预期的。此外，我们首次描述了在补偿进化过程中分离的、对具有不同成本的抗生素耐药性有益突变的分布。因此，这些结果对于理解细菌中抗生素耐药性的传播和维持具有重要意义。
