Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA.
Genome Biol Evol. 2022 Dec 7;14(12). doi: 10.1093/gbe/evac114.
Bacteria, Archaea, and Eukarya all share a common set of metabolic reactions. This implies that the function and topology of central metabolism has been evolving under purifying selection over deep time. Central metabolism may similarly evolve under purifying selection during long-term evolution experiments, although it is unclear how long such experiments would have to run (decades, centuries, millennia) before signs of purifying selection on metabolism appear. I hypothesized that central and superessential metabolic enzymes would show evidence of purifying selection in the long-term evolution experiment with Escherichia coli (LTEE). I also hypothesized that enzymes that specialize on single substrates would show stronger evidence of purifying selection in the LTEE than generalist enzymes that catalyze multiple reactions. I tested these hypotheses by analyzing metagenomic time series covering 62,750 generations of the LTEE. I find mixed support for these hypotheses, because the observed patterns of purifying selection are idiosyncratic and population-specific. To explain this finding, I propose the Jenga hypothesis, named after a children's game in which blocks are removed from a tower until it falls. The Jenga hypothesis postulates that loss-of-function mutations degrade costly, redundant, and non-essential metabolic functions. Replicate populations can therefore follow idiosyncratic trajectories of lost redundancies, despite purifying selection on overall function. I tested the Jenga hypothesis by simulating the evolution of 1,000 minimal genomes under strong purifying selection. As predicted, the minimal genomes converge to different metabolic networks. Strikingly, the core genes common to all 1,000 minimal genomes show consistent signatures of purifying selection in the LTEE.
细菌、古菌和真核生物都具有一组共同的代谢反应。这意味着中心代谢的功能和拓扑结构在长时间的进化过程中受到了净化选择的影响。在长期进化实验中，中心代谢可能也会受到净化选择的影响，尽管尚不清楚这种实验需要进行多长时间（几十年、几个世纪、几千年）才能出现对代谢的净化选择迹象。我假设在大肠杆菌（Escherichia coli）的长期进化实验（LTEE）中，中心和超级必需代谢酶会显示出净化选择的证据。我还假设，在 LTEE 中，专门作用于单一底物的酶比催化多种反应的通用酶表现出更强的净化选择证据。我通过分析涵盖 LTEE 62750 代的宏基因组时间序列来检验这些假设。我发现这些假设得到了混合支持，因为观察到的净化选择模式是特殊的和种群特异性的。为了解释这一发现，我提出了“积木假说”，该假说以一个儿童游戏命名，在这个游戏中，积木从塔上被抽走，直到塔倒塌。积木假说假设，功能丧失突变会降低昂贵、冗余和非必需的代谢功能。因此，复制种群可以遵循失去冗余的特殊轨迹，尽管对整体功能有净化选择。我通过模拟 1000 个在强净化选择下的最小基因组的进化来检验积木假说。正如预测的那样，最小基因组会收敛到不同的代谢网络。引人注目的是，所有 1000 个最小基因组共有的核心基因在 LTEE 中显示出一致的净化选择迹象。
