RT Journal Article
SR Electronic
T1 Optimization of lag phase shapes the evolution of a bacterial enzyme
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 088013
DO 10.1101/088013
A1 Bharat V. Adkar
A1 Michael Manhart
A1 Sanchari Bhattacharyya
A1 Jian Tian
A1 Michael Musharbash
A1 Eugene I. Shakhnovich
YR 2016
UL http://biorxiv.org/content/early/2016/11/16/088013.abstract
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.