BACTERIA USE RULES OF THUMB TO MAKE COMPLEX DECISIONS

To maximize fitness organisms need to make optimal decisions in each environment. However, to calculate such optima in all environments may be an unsolvable task, or at least require computational devices that are so expensive that they reduce fitness. Humans and animals resolve this dilemma by using rules of thumb: practical heuristics that often work but sometimes fail, as demonstrated by Kahenman and Tversky [1] . Knowing about such rules of thumb allows powerful understanding and manipulation of behavior. Here, we ask whether cells also use rules of thumb. We address this using the well-studied carbon utilization system of the bacterium Escherichia coli. Using genetics to uncouple the control circuit, we find that E. coli uses a rule of thumb that yields optimal growth rates in many but not all conditions. Combining theory and experiment to understand the molecular mechanism at play, we re-engineer the circuitry to make sub-optimal carbon sources into optimal ones and vice-versa. Rules of thumb are a conceptual advance that goes beyond the current use of optimality to model cell circuits, and may apply to understand and manipulate a wide range of cellular decision-making processes that are central to health and disease.

[1] Tversky, A. & Kahneman, D. Judgment under Uncertainty: Heuristics and Biases. Science 185, 1124–1131 (1974)