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‘Junk DNA’ theory debunked conclusively

6 September 2012

At least 80 per cent of the human genome is involved in significant biological activity, even though most of it is not made up of genes that code for proteins. A huge research effort culminated last night when 30 papers were published simultaneously across three academic journals; together, they map important DNA interactions across the entire genome, including millions of ‘switches’ that regulate the way different cells interpret the same genetic information.

By sequencing all of our DNA, the Human Genome Project spelled out the 'blueprint of life'; however, far from completing our knowledge of human genetics, it really only established how far we still had to go. We discovered that we understood only a fraction of the sequence and how it operates in our cells.

Among the 3 billion base pairs that make up each person's genetic code, only 2 per cent represented genes that coded for proteins. The rest was a mystery. Some scientists went so far as to dismiss the other 98 per cent as 'junk DNA'.

The Encyclopedia of DNA elements (ENCODE) project was set up in 2003 to identify and characterise all the elements in the human genome that had some function, and so begin to reveal how the genome actually works. Now, after five years of effort by hundreds of researchers, a catalogue of DNA interactions has been published, although data from ENCODE has previously been made available in several free online databases.

The lead researchers describe the ENCODE resource as an operating manual for the human genome. As well as confirming the number of genes that carry the codes to make proteins (around 20 000), they identified another 10 000 genes that have effects in the cell - not through proteins, but through the complementary strands of RNA that are copied from DNA.

In addition, they found 4 million sites in the genome where a protein directly touches DNA, implying a significant degree of regulation by both RNA and proteins over how genes are deployed within different types of cells and at different times.

Ewan Birney, lead analysis coordinator for ENCODE, based at the EMBL-European Bioinformatics Institute on the Wellcome Trust Genome Campus, said: "We've always known there's another set of controls in your DNA that turns genes on and off. We uncovered the control points, or switches, that do this. And there are more switches than we ever thought possible."

Although we are used to the idea of certain genetic variations affecting the risk of developing particular diseases, the ENCODE findings show that many more of these variations are found in areas with a switch than in genes.

Birney described the results of ENCODE as "one of those big steps that has changed my view of the genome fundamentally". Their collective findings demonstrate that the genome is continually having genes turned on and off. Each type of cell requires a different configuration of switches, and the necessary configuration may change with time or in response to events such as infections.

Based at the Wellcome Trust Sanger Institute, the GENCODE Consortium was a vital part of the ENCODE project. Their work described protein-coding genes more accurately than ever before and, more significantly, mapped more than 9000 long non-coding genes, which operate through RNA rather than proteins.

Dr Tim Hubbard, lead principal investigator of GENCODE at the Sanger Institute, said that their findings would contribute to a change in how we think of disease, from a set of symptoms to the underlying mechanisms that produce them. "If the Human Genome Project was the baseline for genetics, ENCODE is the baseline for biology, and GENCODE are the parts that make the human biological machine work," he added. "Our list is essential to all those who would fix the human machine."

The research was announced yesterday at the Science Museum in London, where a new exhibition about ENCODE's work also opened to the public. Called 'Switch to a Different You?', it includes a 3D model of the type of DNA interactions revealed by ENCODE. The exhibit will be on display until 5 December in the 'Who Am I?' gallery, which is supported by the Wellcome Trust, GlaxoSmithKline and Life Technologies Foundation.

Image: A model representing some of the DNA interactions detailed by ENCODE. It is part of the ‘Switch to a Different You?’ exhibit at the Science Museum. Credit: Leo Johnson.


The ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature 2012;489:57-74. doi:10.1038/nature11247

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