One well-known metaphor for the process of biological evolution is ‘tinkering.’ First proposed by François Jacob in 1977 in a now-famous paper in the journal Science, the idea captures two facets of evolution: the fact that new things must be developed from pre-existing things, and the apparent fact that evolution does not proceed with guidance. The picture is one of an actor mindlessly fiddling with implements, tossing them into the mix to see what happens. A believer might prefer the actor to be mindful, perhaps even goal-driven, but the process shows no evidence of this—Hume’s “stupid mechanic” seems a more apt metaphor to me. But mystical preferences aside, a view of evolution as tinkering brings a set of expectations or predictions to evolutionary thought.
One of those predictions is that innovations in evolution should be rare. More precisely, whenever something “new” appears, we expect it to be built from old stuff, from the components already there. No matter how innovative the new thing looks, we expect it to be a subtle reworking of whatever came before.
This brings us to the interesting story of Caulobacter. Caulobacter is the family name of a genus of bacteria with an unusual property: the cells divide asymmetrically. As you probably know, bacteria reproduce without sex—they just divide in two, making an additional copy of the original. They can do this prodigiously (they practically own this planet), but they seem not to be as good at making unique versions of themselves as we are. (Sex is good for that.) In fact, it was long thought (and taught) that bacteria simply clone themselves, with the two daughter cells essentially identical after division. This is true of most bacteria, but Caulobacter is different—cell division in these bacteria creates two very different cells. One is a stalked cell, so named because it sports a stalk and attaches to surfaces, and the other is a swarmer, which is specialized for swimming.
The system that underlies this asymmetric division process has been well worked-out by biologists over the past two decades or so. It all starts with the compartmentalized distribution of signalling components in the mother cell. This leads to distinct signalling outcomes in the two daughters, as you might expect. One of the major cogs in the system is a protein called (ugh) DivK. DivK is a “response regulator” that controls the activity of another protein, DivL. (I didn’t choose the names.) DivL by itself induces conversion to the swarmer type. But DivK (when appropriately activated) blocks this, and without DivL activity the cell becomes (or remains) a stalked cell. On the right is a somewhat helpful diagram from the paper we’ll look at below.
DivL is a wee bit odd. It looks like a kinase, which is a kind of protein (enzyme) that transfers phosphate onto other proteins (this is called phosphorylation). It seems to function that way under some conditions. But it has a single point mutation—a one-letter change—right at a key spot, suggesting that it’s not a normal kinase. And just a few years ago, two groups showed that phosphate transfer is unimportant for DivL to do its main job. Strangely, this kinase doesn’t need to be a kinase to be effective.
In some new work published in the October 2014 issue of PLoS Biology, researchers at Stanford University provide some fascinating context to the strange tale of DivL. Their title says it all: “Cell Fate Regulation Governed by a Repurposed Bacterial Histidine Kinase.”
The scientists looked hard at the structures of DivK and DivL in their complex together, looking for clues about why DivL has that peculiar mutation and whether it ever acts as a kinase. They found that no, DivL does not transfer phosphate (so it’s not a functioning kinase) and that the disabling of this capacity is critical for it to do its job. That job is to regulate the function of signalling components that control the cell-type decision.
This new job is very different from the normal job of kinases like DivL—in fact, it’s a functional reversal of that job. Normally, such kinases phosphorylate the response regulator (recall that DivK is the response regulator in this story), which is then charged with (as the name indicates) regulating responses such as cell division. In Caulobacter, the kinase DivL has been repurposed into a response regulator. Instead of providing the phosphate, it senses the presence of the phosphate on DivK. When there is phosphate on DivK, DivL is engaged and stops conversion into a swarmer cell (so the cell is stalked). Without phosphate on DivK, DivL is free, and activates the conversion into a swarmer.
In plainer terms, tinkering with a normal kinase created a pseudokinase that no longer does kinase work but instead functions as a binary sensor. The change, which is structurally minor, has a remarkable influence on signalling in the cell. The “normal” setup is for the kinase to receive input (via some other signal), then produce output (the phosphorylation of another protein, which is then turned on or off). The setup in Caulobacter is reversed. The input to DivL is already phosphorylated, and the output has nothing to do with phosphorylation. DivL looks so much like a kinase that it is still called a kinase in much of the literature. But in Caulobacter, it has been tinkered into something quite different.
Reuse, recycle, repurpose. We see something new in evolution, in this case a spiffy cell division system that can make two distinct daughter cells. We look harder and see a tinkerer’s handiwork.
Childers, W., Xu, Q., Mann, T., Mathews, I., Blair, J., Deacon, A., & Shapiro, L. (2014). Cell Fate Regulation Governed by a Repurposed Bacterial Histidine Kinase. PLoS Biology, 12 (10) DOI: 10.1371/journal.pbio.1001979