The emergence of a long term stable polymorphism has been shown to require three mutations for one the two partners. Complex epistatic interactions between these mutations and allele specificity appear to be key components in the establishment of the frequency dependency sustaining the stability of the polymorphism.

Ecological opportunities promote population divergence into coexisting lineages. However, elucidation of the genetic mechanisms that enable new lineages to exploit these opportunities has been limited to cases of single mutations. We examined how two E. coli lineages diverged from their common ancestor at the outset of a long-term coexistence. By sequencing genomes and reconstructing the genetic history of one lineage, we showed that three mutations together were sufficient to produce the frequency-dependent fitness effects that allowed this lineage to invade and stably coexist with the other. These mutations all affected regulatory genes and collectively caused substantial metabolic changes. Moreover, the particular derived alleles were critical for the initial divergence and invasion, indicating that the establishment of this polymorphism depended on specific epistatic interactions.

生态机遇可推动种群分化为能够稳定共存的谱系。然而，此前针对新谱系利用此类机遇的遗传机制的阐释，仅局限于单基因突变相关案例。我们针对两个大肠杆菌（E. coli）谱系在长期共存起始阶段从共同祖先分化的过程展开了研究。通过对其中一条谱系进行基因组测序并重构其遗传历史，我们证实：仅需三个突变协同作用，即可产生频率依赖性适合度效应，使该谱系得以入侵并与另一谱系稳定共存。上述突变均靶向调控基因，并协同引发了显著的代谢改变。此外，特定的衍生等位基因对初始分化与入侵过程至关重要，这表明该多态性的建立依赖于特异性的上位性互作。