This is not a screed, or it shouldn’t be. However, the next time you read something about ‘junk DNA’ – check its provenance. It’s true that for years researchers have looked at the huge tracts of genetic material that doesn’t appear to do anything vital (that is, coding for proteins) – which is about 98% of the total DNA – and for lack of any better knowledge called it ‘junk DNA.’ Slowly (and I’m obliged to say) but surely, that pejorative seems to be falling away. The reasons are new studies, such as the one just published in Nature conducted by the U.S. Department of Energy Lawrence Berkeley National Laboratory, which has identified a segment of ‘junk DNA’ where variances increase the risk of coronary artery disease.
The new study builds on previous work showing that a variant (gene or genes) in an interval of DNA (a length of base pairs) on chromosome 9p21 indicates a person has an increased chance of developing coronary artery disease. Explaining the link more precisely was the goal for the new study. They found that the sequence of DNA in this interval regulates a pair of genes that inhibit cell division. When there are bad copies of this sequence (for example, missing some base pairs), the genes’ expression is inhibited. The researchers speculate that without adequate control from these genes, vascular cells proliferate more than normal and eventually narrow the coronary arteries.
“We show that this non-coding interval affects the expression of two cell cycle inhibitor genes located almost 100,000 base pairs away. We believe that something goes awry in variants of this interval, causing vascular cells to divide and multiply more quickly than usual,” says Len Pennacchio, a geneticist with Berkeley Lab’s Genomics Division who conducted the research with Axel Visel and several other scientists from Berkeley Lab, as well as Jonathan Cohen of the University of Texas Southwestern Medical Center.
Berkeley Lab scientists set out to determine the function of the DNA interval in chromosome 9p21 that’s linked to coronary artery disease. They removed an analogous section of DNA from mice, then tracked what happened.
The expression level of two genes located far away, Cdkn2a and Cdkn2b, plummeted by about 90 percent in the “knock-out” mice compared to normal mice. These genes are important in controlling cell cycles and have been linked to cancer when mutated, but they had never been linked to coronary artery disease.
The scientists also studied heart tissue of the “knock-out” mice and found that the smooth muscle cells from their aortas had increased proliferation, a hallmark of coronary artery disease.
The researchers in this study have taken to calling junk DNA ‘non-coding DNA,’ which seems almost as non-informative but may have to do for now. While it should have been dubious that so much DNA would follow the simplistic formula: non-coding DNA = junk DNA, research is just beginning to find ‘other links’ and is a long way from an accurate molecular explanation of the various roles of non-coding DNA.
This one example may have considerable impact on research for heart disease. It will be worth following similar discoveries in the coming years.