Making sense of the extreme makeover for DNA dark matter: from genomic ‘junk’ to treasure trove

The fields of science related to DNA have for a long time been gene-centric.

By this I mean that most scientists working in these areas have focused their attention and their efforts on the genes that make the proteins and RNAs that are the workers of the cell. What’s left over that wasn’t genes mainly wasn’t consider worth studying.

In this way of thinking all the DNA in our genomes that was not the part containing the genes was thought of as ‘junk’ or ‘dark matter”. Some scientists viewed it as a wasteland and a waste of time.

However, I always thought that was narrow-minded. In fact, I was taught in grad school that the component of our genome that wasn’t genes likely had many important functions that we just didn’t quite understand yet, but we would in the future. Then later when I was a postdoc at the Hutch in Seattle I learned more about the genome and some of the wise folks there felt sure that this non-genic “dark matter” contained many elements regulating expression of the genes. In other words, the genome had genes and then much of the rest was not junk, but rather contained the switches that controlled how active the genes were. Mad sense.

Today, scientists working together to explore the genome in a project called ENCODE have taken a big leap forward in our understanding of the dark matter of the genome and indeed it has great functional significance for regulation of the activity of genes. As usual, Gina Kolata of the NY Times does a great job in her article today explaining this as she does on many complex scientific topics. A video on ENCODE that is very helpful (see at top of post) is also available.

In a literal flood of new science papers from ENCODE (just a few of dozens can be seen here in Nature along with more background on ENCODE), many in top journals, a massive team of scientists report collectively via a project known as ENCODE on a new model for what used to be called ‘junk’ DNA. In this new way of thinking, the DNA not containing genes is critically important because it contains about a million so-called “switches” that control the expression of the approximately 21,000 human genes. In other words, without all these switches, the genes in cells would turn on or off pretty much randomly. Some might stay off forever when they should be on and vice versa. Often such glitches occur in diseases and some of the papers touch on this.

As a result, the ‘junk” DNA turns out to be, quite to the contrary of its old name, in actuality a treasure trove of regulatory elements by which gene expression and in turn protein expression are adjusted in cells.

No wonder that much of this “junk” DNA is actually evolutionarily conserved…evolution doesn’t conserve things without a functional reason.

For better or worse, it turns out these million regulatory switches are mindbogglingly complex. One scientist, Erik Lander, was quoted that “My head explodes at the amount of data.”

However, despite the complexity the new papers at least help us scientists better understand where to begin digging further and open many new doors to a better understanding of human health. I find all of this really exciting.

The scientists involved in ENCODE also stress that there is still more of the genome that isn’t genes and isn’t switches….I’m betting that remaining “dark” parts of the genome are also not junk, but rather something we still don’t understand…at least not yet.

Stay tuned.