No Longer Useless: The Important Roles of ‘Junk DNA’

When geneticists started mapping the human genome, they were specifically interested in learning about genes and what they do. Everything else they deemed as “junk DNA.”

But as the saying goes, one person’s trash is another person’s treasure.

So-called junk DNA makes up the vast majority of the genome — about 98% — and consists of non-coding DNA, which scientists now see as vital to studying human health and disease.

“In modern, more enlightened times, we realize that while genes, the protein-coding units of the genome, are very important, they cannot perform their jobs without the very complex regulatory functions of non-coding regions of the genome,” explains Iain Konigsberg, PhD, research instructor in the Department of Biomedical Informatics at the University of Colorado School of Medicine.

He shares what exactly junk DNA is and why associating non-coding DNA with junk no longer makes sense in the world of disease research.

What does the term “junk DNA” mean?

Historically speaking, non-coding DNA was coined “junk DNA” by some people working in genomics a few decades ago.

DNA contains genes, which encode proteins. Geneticists think of genes as the basic units of the genome, and years and years ago, there was a lot of focus in the field of gene discovery to identify individual genes. They were basically looking for needles in a haystack, but they weren’t much interested in the haystack.

However, just because there wasn’t interest in that part of the genome at the time doesn’t mean there wasn’t any significance. We now see that non-coding DNA, or what was previously considered junk, has many important roles.

So, individual genes rely on non-coding DNA?

For the most part, yes.

A lot of work since the Human Genome Project has shown that defining these non-coding regions of the genome as junk does them a disservice. While genes are the major units of the genome that become functional proteins, these genes can't really perform their functions without the non-coding DNA.

What roles do non-coding regions of the genome play?

They have important jobs like determining the 3D architecture of DNA, or how it folds. The sequences within these regions can be involved in protein binding and protein recruiting, DNA contacts, and more.

One of the primary mechanisms a lot of us researchers are interested in is that these regions contain sequences that are known to affect gene activity. There are regulatory elements within non-coding DNA. A few popular and commonly discussed ones are enhancers and repressors.

Does non-coding DNA impact disease?

Absolutely. Generally in genetic diseases, we see two types: mendelian disease and common complex disease. Mendelian diseases are driven by high effect size variations or mutations. Those tend to occur in coding DNA. For example, Huntington’s disease is associated with the Huntington gene, and if you have variants that affect this gene’s activity, you likely have this disease.

But there is a lot of genetic variation that doesn’t have that large of an effect. We see a lot more variation generally in non-coding DNA regions, and these regions are less constrained.

All of us are carrying around a lot of variation in our non-coding DNA. One variant isn't typically going to give us a lifelong disease, but burdens of these variants can start to impact our health.

For these common diseases that are often also impacted by the environment — let's think about things like type two diabetes or coronary artery disease — there are a lot of variants in the non-coding genome that affect your risk of these diseases very, very slightly. A lot of the diseases that faculty and researchers in our department focus on don’t have these simple on-and-off switches. There’s a spectrum of risk, which comes from those non-coding DNA regions.