Experimental Evolution Reveals Unifying Systems-Level Adaptations but Diversity in Driving Genotypes
Erol Kavvas, Christopher P. Long, Anand V. Sastry, Saugat Poudel, Maciek R. Antoniewicz, Yang Ding, Elsayed T. Mohamed, Richard Szubin, Jonathan M. Monk, Adam M. Feist, Bernhard Ø. Palsson
Abstract
Understanding the mechanisms of microbial adaptation will help combat the evolution of drug-resistant microbes and enable predictive genome design. Although experimental evolution allows us to identify the causal mutations underlying microbial adaptation, it remains unclear how causal mutations enable increased fitness and is often explained in terms of individual components (i.e., enzyme rate) as opposed to biological systems (i.e., pathways). Here, we find that causal mutations in E. coli are linked to systems-level changes in NADPH balance and expression of stress response genes. These systems-level adaptation patterns are conserved across diverse E. coli strains and thus identify cofactor balance and proteome reallocation as dominant constraints governing microbial adaptation.