Tuesday, February 2, 2010

Tunable Flexibility

Some genes can't be substantially changed without fatal consequences, while tweaking other genes lets organisms gracefully adapt to new situations.

This modular organization, in which some groups of components maintain a fixed relationship to one another even as the relationship between groups changes, is common in biology. In their book, The Plausibility of Life, Marc Kirschner and John Gerhart argue that the weak linkages between unchanging modules are a critical ingredient of "facilitated variation," which in turn makes rapid, dramatic evolution possible. But this long-term adaptability may be, in part, a fortunate side effect of a system that lets individual organisms respond to changes during their lifetime.

Natural selection is not based on compassion. It would be reasonable if both essential genes--those within modules--and nonessential genes--including those forming the weak linkages between modules--mutated equally readily. A mutation within a module might kill its host, but that's the way of progress. Mutations of the linkages could survive, and, by altering the relationship between modules, allow a population to explore new innovations.

Evolution would be more efficient if genes within modules didn't mutate as quickly as those between them. But it's not required.

But what if the evolvability is just one facet of a more general flexibility? At a December 2009 meeting in Cambridge, MA, which I'm covering for the New York Academy of Sciences, Naama Barkai of the Weizmann Institute in Israel showed evidence that genes that evolve rapidly also show greater variability in expression.

To measure the rate of evolution, Barkai's postdoc Itay Tirosh compared different yeast species to see which genes had the most differences. Some genes differed a lot, while others were quite similar.

Tirosh also looked at two measures of the intrinsic variability of gene expression (measured by messenger RNA levels): the degree of change in response to changed conditions, like stress, and the time-dependent variation in expression, or noise. Again, some genes varied a lot, while others stayed quite steady. Moreover, the variable genes were likely to be the same ones that evolved rapidly.

These three correlated measures of gene flexibility were connected with differences in the structure of the promoter, which is the region of DNA near where its transcription into RNA begins. Flexible genes tended to include the well-known "TATA" sequence of alternating tyrosine and adenosine bases, as well as different arrangements of the nucleosomes.

A complete understanding of the role of flexibility in both short- and long-term variation will require a lot more research. But these results support the notion that arrangements that let organisms adapt to the slings and arrows of everyday life also give them the tools to rapidly evolve dramatically new ways of life.

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