The scientific community is abuzz with the publication of 30 articles in Nature and other journals (Genome Research and Genome Biology) resulting from the Encode project. As Gina Kolata reports in New York Times,
The human genome is packed with at least four million gene switches that reside in bits of DNA that once were dismissed as “junk” but that turn out to play critical roles in controlling how cells, organs and other tissues behave. The discovery, considered a major medical and scientific breakthrough, has enormous implications for human health because many complex diseases appear to be caused by tiny changes in hundreds of gene switches.
The findings are the fruit of an immense federal project, involving 440 scientists from 32 labs around the world. As they delved into the “junk” — parts of the DNA that are not actual genes containing instructions for proteins — they discovered it is not junk at all. At least 80 percent of it is active and needed.
The result is an annotated road map of much of this DNA, noting what it is doing and how. It includes the system of switches that, acting like dimmer switches for lights, control which genes are used in a cell and when they are used, and determine, for instance, whether a cell becomes a liver cell or a neuron.
There are only about 21,000 genes that code for proteins, which constitutes a tiny proportion of the human DNA. Previously it was thought that 99 percent of DNA in the human genome didn’t do anything – it was ‘junk.’ Now it appears that most of it is actually functional – but in a very strange way.
The human genome resembles an army that has 21,000 privates and millions of generals that tell privates (and each other) what to do.
Visualizations of networked linkages between genetic components across the human genome (right) and in a smaller subset (left). (Image: Gerstein et al. in Nature)
What I find striking is that much of the action – both in terms of selection responses, and also in responses to environmental influences, or aging – is in the vast network of regulatory genes. My experience with such massively nonlinearly connected systems is that it is very difficult to manipulate them to achieve a desired outcome, and it is very easy to get unintended – and undesirable – consequences via nonlinear feedback loops.
This reminds me of a conversation I had with the evolutionary biologist Michael Rose in April at the Consilience conference in St. Louis. As I wrote in my blog on why I decided to switch to the (so called) Paleo diet:
The reason is that one gene-one action model is wrong; it’s not how our bodies work. Most functions are regulated not by a single gene, but by whole networks of them. As we age, some genes come on, and others go off, and the network changes, often in very subtle and nonlinear ways.
The new results from the Encode project appear to be a dramatic confirmation of this view.