Phenotypic heterogeneity and the evolution of metabolic cross-feeding interactions

在微生物世界中，两个或多个个体交换昂贵的代谢产物的合作交叉喂养非常常见。然而，将代谢物释放到外部环境中很难与自然选择相协调：自私的突变体预计将在没有回报的情况下进化和利用公共利益，从而威胁到这些合作相互作用的完整性。申请人先前的工作表明，在两种不同氨基酸营养缺陷型的两种大肠杆菌基因型之间迅速进化出合作性交叉摄食相互作用。经过8周的共培养，营养缺陷型聚生体获得了显着增加的健身，这是由于增强的氨基酸生产水平。有趣的是，衍生的聚生体始终表现出广泛程度的表型异质性，这与多细胞簇的形成相吻合。假设在集群间水平上的选择导致了这种模式，拟议的项目旨在确定所观察到的异质种群的生物学意义。为此，将组装属于三种细菌物种之一的营养缺陷型基因型对。实验共同进化的结果内和种间组合将允许确定遗传相关性的影响，形成多细胞簇，并确定在此过程中的表型异质性的产生所起的作用。通过结合基于个体的建模，单细胞水平上的微观分析，以及对衍生表型的详细调查，可以获得对塑造合作交叉喂养相互作用演变的动态的前所未有的机械见解。

Cooperative cross-feeding, in which two or more individuals exchange costly metabolites, is very common in the microbial world. However, a release of metabolites into the external environment is difficult to reconcile with natural selection: selfish mutants are expected to evolve and exploit the public good without reciprocating, thus threatening the integrity of these cooperative interactions. Previous work of the applicant has shown that cooperative cross-feeding interactions rapidly evolved among two Escherichia coli genotypes that were auxotrophic for two different amino acids. After only 8 weeks of coculture, auxotrophic consortia gained a significant increase in fitness, which was due to enhanced amino acid production levels. Interestingly, derived consortia consistently showed an extensive degree of phenotypic heterogeneity, which coincided with the formation of multicellular clusters. Hypothesizing that selection on a between-cluster level caused this pattern, the proposed project aims at identifying the biological significance of the observed heterogeneous populations. For this, pairs of auxotrophic genotypes belonging to one of three bacterial species will be assembled. Experimental coevolution of the resulting intra- and inter-specific combinations will allow to determine the impact of genetic relatedness on the formation of multicellular clusters and identify the role the generation of phenotypic heterogeneity plays during this process. By combining individual-based modelling, microscopic analyses on a single-cell level, and a detailed investigation of derived phenotypes, unprecedented mechanistic insights into the dynamics that shape the evolution of cooperative cross-feeding interactions can be gained.