A Quiet Revolution in Genetic Science


There has been a quiet revolution in genetic science over the last two years, resulting in a landslide of new papers and a profoundly different understanding of how DNA works. The new understanding may be as important as Watson and Crick’s explanation of the structure of the DNA molecule back in 1953.

There are two parts to the new discoveries. The first involves the “junk DNA” in the long strands of molecules that make up chromosones. It’s long been known that the DNA molecules encode genes, the inherited traits the define an organism. But there were long series of “dark matter,” non-encoding, non-gene between the genes themselves on the spiral staircase of the DNA molecule.

Animation of rotating DNA structure

Animation of rotating DNA structure

The “dark matter” was dismissed as “junk DNA” and largely ignored. Science focused on the genes.

That turns out to have been an error. All that “dark matter” turns out to be a nearly unbelievably complex series of switches that regulate when and how the genes are expressed in an organism. There are as many as a million “switches” in that dark matter that regulate the behavior of the 21,000 genes in the human genome. Instead of only  five to ten percent of human DNA being used, essentially all of it is being used.

Many genetic diseases turn out to be errors in these switches, not errors in the genes themselves. Diseases like multiple sclerosis, lupus, rheumatoid arthritis, Crohn’s disease, celiac disease now seem to result from switching errors, not problems with the genes. So it may be that treatments can be developed that address the switches, and not the genes.

The complexity of the genetic switching system in the “dark matter” is daunting. The effort to sort out the complexity is at ENCODE, the Encyclopedia of DNA Elements. ENCODE is the work product of some 440 scientists from 32 labs around the world.

The second part of the new discoveries involves that describe how ten feet of DNA molecules – 23 chromosome pairs – get packed into a cell nucleus that is one hundredth of a millimeter in diameter. While we think of the DNA molecule as the spiral staircase shown in the illustration, in fact it is folded and packed unbelievably tightly. It’s called “fractal globule” packing, and the information content is trillions of times higher than the most advanced computer chip. The cells separate the most active genes into their own special neighborhood, to make it easier for proteins and other regulators to reach them.

The folding places the genes affected by specific genetic switches in close proximity to the genes, even though if you were to straighten out the DNA molecule they might be quite far apart. There’s some suggestion that individual cells specialize by how the DNA is folded. The DNA can easily unfold and refold during gene activation, gene repression and cell replication. So the mystery of how cells specialize to perform the myriad tasks they do may be a matter of selective folding and “dark matter” directing the specialization.

There are going to be a boatload of papers published over the next few months that begin to untangle this complex process. We may be on the eve of solving a lot of longstanding puzzles, and finding cures to some intractable diseases.

Exciting times.