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A gene network tuned to a critical point?

Measurements of correlations in gene expression levels reveal striking behavior.

It's largely a mystery how an organism conveys to its constituent cells which of its genes should be active, but some pieces of the puzzle are known. For example, in developing fruit-fly embryos, so-called gap genes are involved in telling cells where they're positioned between the head and the tail. The gap genes are known to be mutually repressive: High levels of the protein encoded by one inhibit the expression of the others. But the quantitative details of that interaction, and how it gives rise to the same distinctive protein pattern in every embryo, are unknown. Now Princeton University theorists William Bialek and Dmitry Krotov argue that the gap-gene network may be operating at a critical point, defined, in general, as a division in parameter space between regimes of qualitatively different behavior. In the case of the gap genes, the critical point divides the monostable regime, in which pairs of genes interact weakly and have a single steady-state output, from the bistable regime, in which the genes repress each other strongly and exhibit switch-like behavior. A universal feature of a two-gene network at criticality is a strong anticorrelation between fluctuations in the two genes' expression levels. Indeed, in some regions of the fruit-fly embryo where only two of the gap genes are significantly expressed, the correlation coefficient between the two active genes approaches −1. Looking further into the question of how and why evolution would guide a system toward critical behavior could lead to new insights into the nature of life. (D. Krotov et al., Proc. Natl. Acad. Sci. USA, in press.)—Johanna L. Miller


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