I have recently finished reading a Nature news feature on noise in gene expression (The Cellular Hullabaloo). It left me with this increased understanding of cellular processes and in terms of controlling chaos, fitted nicely with something I have blogged about before, which is Hsp’s (especially Hsp90).
According to this news feature, several studies have found that there are significant differences in the expression of genes both in duration and strength, even between cells that were expected to be identical. This contradicts the current notion of gene expression as an orderly sequential and structured phenomenon. These studies seem to indicate that gene expression occurs randomly, throughout the whole genome.
How these cells are still able to differentiate in a predictable manner,…… and perform specialized functions in concert with thousands of other cells,…….. to build a functional multicellular organism, is a mystery to me. And it is enigmatic to the researchers behind these studies as well:
“People are fascinated by how we do what we do despite this noise.” — James Collins
“People ask how come an organism works so well. Perhaps it doesn’t work so well. Perhaps organisms without these fluctuations would outcompete us.” – Johan Paulsson
How the noise came about and why it persists is still somewhat unclear, but benefits from such chaotic conditions may arise from:
1. Controlling randomness (noise) requires a lot of energy, the more chaos the less energy spent. Consequently, only the most critical cellular processes are under tight control, and the rest are more or less random.
2. Expression noise may enable cells to fight off threats. Say a certain level of protein is required to survive a toxic compound attack. Then having cells with sufficient levels of defender protein is more probable in a (noisy) cell population with varying gene expression levels, than in cell populations with a constant level of expression.
3. Randomness may ensure variation in differentiation. An example given in the news feature is the differentiation of blue and green light sensing photoreceptors in drosophila.
So, the noise is there for a reason. Noise, or more precisely – random fluctuation, is an ubiquitous cellular phenomenon. But cells of a given type still end up with similar morphology and similar functionality. The beauty of nature is how the randomness is controlled just enough to achieve the minimum amount of order necessary for preserving functionality. Also, in keeping the random events, flexibility is preserved for future adaptation.
The chaos extends further than gene-expression. If you also consider variations in insertions/deletions, gene copy number and epigenetic differences, the potential for random variation at the gene level becomes evident. To control some of this genetic randomness you have proteins like Hsp90 that masks genetic variation at the transcription level (or folding level to be precise). This is an important control-mode for some of the chaos (DNA sequence variation and mutations) and at the same time it enables sudden exposure of chaos to achieve rapid morphological evolution if needed. I am pretty sure that similar (or very different) control mechanisms will be discovered for gene expression noise in the future.
The noisy expression story is another illustration of how we are not just our genes. The DNA-sequence may be a defining starting point, but there are levels and levels of variation on top of that. As multicellular and evolving organisms, we are constantly balancing between chaos and order. The chaos-level is maximized to minimize energy expenditure and to ensure a multitude of possible paths to follow in an organisms future biological evolution.
The balance is oh so beautiful, it’s called nature.