Experimental Evolution Reveals Unifying Systems-Level Adaptations but Diversity in Driving Genotypes

Area of Science:

• Microbial evolution and systems biology.
• Genomics and adaptive laboratory evolution (ALE).

Background:

• Genotype-fitness maps are well-defined for molecular components but less so for systems like metabolic and transcriptional networks.
• Understanding microbial adaptation mechanisms is crucial for combating drug resistance and enabling predictive genome design.

Purpose of the Study:

• To investigate systems-level properties of microbial adaptation using multi-omics data from E. coli.
• To characterize the link between causal mutations and systems-level adaptations during adaptive laboratory evolution.

Main Methods:

• Multi-omics measurements (genomics, transcriptomics, metabolomics) of 6 E. coli strains during adaptive laboratory evolution (ALE).
• Analysis of phenotypic convergence/divergence, transcriptomic adaptations, regulatory trade-offs, and mutation-correlates.

Main Results:

• Phenotypic convergence observed across strains, except for NADPH production mechanisms, which showed divergence.
• Conserved transcriptomic adaptations include increased expression of growth genes and decreased expression of stress/structural genes.
• Identified regulatory trade-offs and correlations linking causal mutations to systems-level changes in NADPH balance and proteome reallocation.

Conclusions:

• Fitness landscapes in ALE are shaped by two layers of causation: system-level properties and discrete mutations.
• Cofactor balance (NADPH) and proteome reallocation are dominant constraints governing microbial adaptation in E. coli.
• Findings provide insights into conserved adaptation patterns across diverse microbial strains.