“If the cell had an infinite amount of energy it would just dump very high levels of all these proteins together right away,” says Alon. “But bacteria are limited by protein synthesis. In this economy they need to make tradeoffs.”
Alon's group investigated the tradeoffs using 52 gene fusions to fluorescent proteins. They found that genes encoding early steps in a pathway are turned on both earlier and more aggressively, thus ensuring that later gene products have a sufficiently high concentration of substrate on which to act. A computer program designed to optimize production in a mathematical model of a similar pathway came up with a strategy that had the same two dynamic principles.
The “just in time” approach—ordering transcription based on when the gene products are used—has been seen in pathways controlling development and phage and flagellum assembly. For the flagellum case, others have shown that the ordering correlates with the varying affinity of a single transcription factor; in an upcoming issue of Cell, Alon's team reports that the order can be changed with simple point mutations in the flagellum promoters. ▪