Epistatic interactions determine the mutational pathways and coexistence of lineages in clonal Escherichia coli populations

Understanding how diversity emerges in a single niche is not fully understood. Rugged fitness landscapes and epistasis between beneficial mutations could explain coexistence amongst emerging lineages. To provide an experimental test of this notion, we investigated epistasis amongst four pleiotropic mutations in rpoS, mglD, malT and hfq present in two coexisting lineages that repeatedly fixed in experimental populations of Escherichia coli. The mutations were transferred into the ancestral background individually or in combination of double or triple alleles. The combined competitive fitness of two or three beneficial mutations from the same lineage was consistently lower than the sum of the competitive fitness of single mutants – a clear indication of negative epistasis within lineages. We also found sign epistasis (i.e. the combined fitness of two beneficial mutations lower than the ancestor), not only from two different lineages (i.e. hfq and rpoS) but also from the same lineage (i.e....人们对于单一生态位（niche）中多样性的产生机制尚未完全阐明。崎岖适应度景观（rugged fitness landscapes）与有益突变间的上位性（epistasis），或可解释新兴演化支之间的共存现象。为对这一假说开展实验验证，我们针对大肠杆菌（Escherichia coli）实验种群中反复固定的两个共存演化支内的4个多效性突变（pleiotropic mutations）展开上位性分析，这4个突变分别位于rpoS、mglD、malT及hfq基因中。我们将这些突变以单个等位基因、双等位基因组合或三等位基因组合的形式，分别转入祖先遗传背景中。结果显示，来自同一演化支的2个或3个有益突变的联合竞争适合度，始终低于各单突变体竞争适合度的总和——这清晰表明同一演化支内存在负上位性（negative epistasis）。此外我们还观察到了符号上位性（sign epistasis，即两个有益突变的联合适合度低于祖先菌株），这种现象不仅出现在来自不同演化支的突变组合（如hfq与rpoS）中，也存在于同一演化支的突变组合（即……）