Noise in gene expression at Gene Expression

New(ish) writer Coffee Mug at GNXP (see update) has been busily at work writing minireviews of long-term potentiation and gene expression itself.

The post on gene expression focuses on the problem of noise. Noise is generally conceived as variation in a received signal compared to its source. As applied to the level and timing of gene expression, the "source" is the genes, which are themselves products of past selection. As we all know, genes specify the production of proteins by encoding amino acid sequences; they also specify when and where to produce said proteins by means of promoter sites and the like.

The "noise" is therefore unspecified variation in expression. A gene may have regulatory cascades that specify its activation in a certain tissue. But if one of the regulatory molecules has another role in a different kind of tissue, a slight leakage of expression of the gene may occur there as well. Or a gene may be inhibited by the presence of a certain molecule, but variation in the concentration of the molecule (or of others that counteract the molecule) may vary. Natural selection can reduce this "noise" by reducing the tolerance of genes for unspecified activation, or by heightening the thresholds for expression. But often it doesn't.

After some very good examples of experiments intended to tease out the noise in gene expression, the post leads to the evolutionary point:

So, to recap: 1) prokaryotes have noisy translation because their transcripts are fought over by RNases and ribosomes. 2) Eukaryotes have noisier transcription because activation of promoters leads to pulses of mRNA production, but 3) this varies from promoter to promoter.
Now... Why would it vary? This is how we come full circle. There are two rationales for having a noisy gene. First, it may not have been that important to refine the noisiness of the gene. It's expensive to build in more precise control circuitry, and if you don't need it, then you don't need it - sell the darn camera. On the other hand, what if it were a trait that didn't need to be precisely regulated, thus was allowed to stick around and be noisy, thus provided variation in a phenotype amongst a monoclonal population? Would that give an advantage to the noisy population of clones in a time of stress? A time where the selection pressures were a little more specific? Is noise a way to allow organisms to hedge their bets when selection isn't currently holding their feet to the fire on a particular issue? Many think so.

It is worth pointing out that "noise" is different from "plasticity" -- although a noisy system certainly be plastic, "noise" by itself does not imply the possibility of an adaptive response, while plasticity often encompasses "fitting" of the environment. But the analogy in this case with "overspecialization" is tempting -- the idea that some organisms may be so highly adapted to a narrow niche that they are doomed in the long term. In the case of noisy gene expression, the idea would be that organisms with highly fine-tuned expression might lack the ability to compete effectively outside of the narrow tolerances.

The observation that essential genes in yeast appear to have less noisy expression than less essential genes does seem to support this point of view. I like the idea a lot, and I've been thinking about it some in a different context. (My post from last week quoting Claude Shannon wasn't just happenstance!)

So it is fair to point out some alternatives to consider. For one, a substantial variance in gene expression might well be compatible with strong selection on the timing, location, and level of gene activation -- if that selection tends to occur discontinuously instead of continuously. Too much expression at a critical time might result in death, but most times may not be critical in that way. Or a small excess in the concentration of a gene product might make little difference, but over a threshold it might result in early maturation, or infertility, or any number of other bad things.

That leads to an interesting question of the relative continuity of environment and organismal response. How direct is the feedback between the expression of a gene and its adaptive consequence?

I also have to wonder, is this really about "noise"? Unlike many genetic things, gene expression is a perfectly good quantitative phenotype -- like the length of a bone. Some bony dimensions are more variable than others -- but does that mean they are more "noisy"?

To my eyes, the recent gene expression results from human tissue are just immense in the extent of their variation -- to the extent that within-human variation in expression levels is for many tissue types substantially greater than the average human-chimpanzee difference. Again, not too surprising for a phenotypic trait -- the same is true of many bony dimensions.

Perhaps more than anything, this is an analogical shortfall. We are used to the idea that genetic information is digital -- present or absent, G, A, T or C. Protein sequences are coded with the high fidelity of a CD. But throw in a continuous time dimension and a huge number of cells, and the idea of perfect digital fidelity is simply not possible. Instead, we face the continuous information problem, in which the best fidelity achievable is a question of what level of error we are willing to tolerate. Of course, this is true even in the absence of noise -- no biological channel is infinite, and selection can increase fitness only by steps.

Maybe if each of our cells had Maxwell's demon watching...

UPDATE (5/25/2006): Coffee Mug adds:

Note that the real author of the noise post was not me (Coffee Mug), but a friend of mine who goes by deadsmith, when he goes by internet names..