Environmental pleiotropy and demographic history direct adaptation under antibiotic selection.

Environmental pleiotropy and demographic history direct adaptation under antibiotic selection.
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DOI:
10.1038/s41437-018-0137-3
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发表时间:
2018-11
期刊:
影响因子:
3.8
通讯作者:
Knight CG
Knight CG
中科院分区:
生物学2区
文献类型:
--
作者:
Gifford DR;Krašovec R;Aston E;Belavkin RV;Channon A;Knight CG

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环境变化后的进化拯救需要突变,允许新环境中的人口增长。如果变化严重到足以阻止大多数种群的繁殖,那么救援就依赖于已经存在的突变。如果变化是持续的,在两个环境中的适应性效应,以及它们是如何关联的--被称为“环境多效性”--可能决定哪些等位基因最终受到青睐。一个种群的人口统计学历史--其规模随时间的变化--影响着当前的变化。虽然人口统计学的历史是众所周知的,影响进化的可能性救援,它如何与环境多效性在严重和持续的环境变化的相互作用仍然是未知的。在这里,我们展示了这些因素如何在抗生素耐药性进化过程中相互作用,这是由具有多效性适应性效应的预先存在的突变推动的进化拯救的一个关键例子。我们结合联合收割机发表的数据与新的模拟,以阐明环境多效性及其对不同人口历史下的抗性进化的影响。抗性等位基因之间的比较通常显示与适合度没有相关性,中性多效性-高于和低于敏感菌株的最低抑菌浓度。实验进化后的抗性等位基因频率与抗生素存在和不存在下的适应性效应表现出相反的相关性。模拟结果表明,环境多效性对等位基因频率的影响取决于人口统计学史。在种群水平上,环境多效性的主要影响是平均适应度,而不是进化拯救或多样性的概率。我们的工作表明,确定环境多效性和人口统计学的历史是至关重要的预测耐药演变,我们讨论了在体内进化过程中的实用性。
Evolutionary rescue following environmental change requires mutations permitting population growth in the new environment. If change is severe enough to prevent most of the population reproducing, rescue becomes reliant on mutations already present. If change is sustained, the fitness effects in both environments, and how they are associated—termed ‘environmental pleiotropy’—may determine which alleles are ultimately favoured. A population’s demographic history—its size over time—influences the variation present. Although demographic history is known to affect the probability of evolutionary rescue, how it interacts with environmental pleiotropy during severe and sustained environmental change remains unexplored. Here, we demonstrate how these factors interact during antibiotic resistance evolution, a key example of evolutionary rescue fuelled by pre-existing mutations with pleiotropic fitness effects. We combine published data with novel simulations to characterise environmental pleiotropy and its effects on resistance evolution under different demographic histories. Comparisons among resistance alleles typically revealed no correlation for fitness—i.e., neutral pleiotropy—above and below the sensitive strain’s minimum inhibitory concentration. Resistance allele frequency following experimental evolution showed opposing correlations with their fitness effects in the presence and absence of antibiotic. Simulations demonstrated that effects of environmental pleiotropy on allele frequencies depended on demographic history. At the population level, the major influence of environmental pleiotropy was on mean fitness, rather than the probability of evolutionary rescue or diversity. Our work suggests that determining both environmental pleiotropy and demographic history is critical for predicting resistance evolution, and we discuss the practicalities of this during in vivo evolution.
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