PT  - JOURNAL ARTICLE
AU  - Bharat V. Adkar
AU  - Michael Manhart
AU  - Sanchari Bhattacharyya
AU  - Jian Tian
AU  - Michael Musharbash
AU  - Eugene I. Shakhnovich
TI  - Optimization of lag phase shapes the evolution of a bacterial enzyme
AID  - 10.1101/088013
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 088013
4099  - http://biorxiv.org/content/early/2016/11/16/088013.short
4100  - http://biorxiv.org/content/early/2016/11/16/088013.full
AB  - Mutations provide the variation that drives evolution, yet their effects on fitness remain poorly understood. Here we explore how mutations in the essential enzyme Adenylate Kinase (Adk) of E. coli affect multiple phases of population growth. We introduce a biophysical fitness landscape for multiple phases of bacterial growth, which shows how they depend on molecular and cellular properties of Adk. We find that Adk catalytic capacity in the cell (product of activity and abundance) is the major determinant of mutational fitness effects. We show that bacterial lag times are at an optimum for the endogenous enzyme, while exponential growth rates are only weakly affected by variation in Adk. Direct pairwise competitions between strains show how environmental conditions modulate the outcome of a competition where growth rates and lag times show a tradeoff, altogether shedding light on the multidimensional nature of fitness and its importance in the evolutionary optimization of enzymes.