Arrival of the Fittest by Andreas Wagner

Author:Andreas Wagner
Language: eng
Format: epub
Publisher: Penguin Group, USA
Published: 2014-09-16T16:00:00+00:00

These examples and hundreds more illustrate the power of regulation to innovate. The lab notebooks of thousands of researchers and the pages of dozens of scholarly journals are overflowing with research on regulators like KNOX in plants, distalless in butterflies, and engrailed in fruit flies. Our own genome encodes more than two thousand different regulators in dozens of separate circuits.37 A half century of research has told us how important regulation is to building bodies old and new. It has helped us to understand the natural history of many innovations and the new expression codes behind them.

But a list of examples, however long, cannot go beyond that. Lizards’ limbs and fishes’ fins are shaped by different variants of Hox circuits—different circuit genotypes—that produce different expression codes. Identifying any one such circuit variant does not explain how evolution found the one whose expression code is best suited for a task. (If there are too many circuit variants, this could be impossibly hard.) What’s more, while circuits change little by little in evolution, useful expression codes need to be preserved before new and better ones are found. No list of examples, however long, could tell us how innovation through regulation is even possible.

If the problem is familiar, so is the solution: Study not just one circuit but many, an entire library of circuit genotypes and their expression phenotypes. The texts in this regulation library are the DNA genotypes that encode regulators and the words they recognize. But writing them like that would be unnecessarily long and tedious, as if you described a house through the position of all its molecules, rather than by an architect’s blueprint. Much better to write them as wiring diagrams like those of figure 16.

The entire library comprises all possible such circuits—all possible wiring diagrams. To compute its size we need to count these wiring diagrams. That may seem hard, but it is surprisingly easy. Any regulator in a circuit, call it A, can influence another regulator, B, in three principal ways. Regulator A can activate B, it can repress it, or it can have no effect. The same holds for any other pair, say, A and C, or D and E, in the circuit of figure 16. One can activate the other, repress the other, or have no effect on it. These are the only three options. This simple idea takes us almost all the way to counting all five-gene circuits. What’s left is to count the number of gene pairs. The circuit of figure 16 has 5 × 5 = 25 of them, each with three regulation options.38 To find the total number of circuits, we then need to multiply three for the first gene pair with three for the second gene pair with three for the third pair, and so on, for all twenty-five pairs. Three multiplied with itself 25 times yields 325, or more than 800 billion circuits.

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