Junk DNA: the "software" of life?
A section of the complex RNA network proposed by Mattick (Pic: EMBO Reports)
"Junk DNA" is actually the "software" that allowed complex organisms to evolve, according to an Australian molecular biologist.
Professor John Mattick of Queensland University's Institute of Molecular Bioscience argues that scientists have been too focused on the protein-production role of DNA and ignored its role in helping to put all the proteins together at the right time and place.
"The genetic program has to do two things," said Professor Mattick. "It has to specify the protein components, the bricks if you like, but it also has to specify the patterns in which those things are put together."
Traditionally, scientists have written off non-protein-coding DNA as "junk". Professor Mattick sees it differently.
"Only a minority of the human genome codes for protein," he said. "The majority is coding for very sophisticated plans which are mainly expressed through a non-coding RNA network."
Professor Mattick argues that this RNA communication network enables co-ordination and integration during an organism's differentiation and development.
"This is the software of the system, and once you understand what it is, eventually you will know how to manipulate the software to change the length of fingers or the shape of a nose."
"If what I'm saying is correct, it's going to mean a total re-appraisal of our understanding of genetic systems in higher organisms."
He said one example of the role of non-coding RNA is the XIST gene. This doesn't make a protein but produces an RNA molecule that coats and shuts down one of the female's X chromosomes before birth. This is necessary so that females and males have the same amount of X chromosome expression.
He said understanding RNA networks will shed better light on what makes us more vulnerable to environmental triggers for disease.
"So far people have not been able to identify the genetic components underlying predisposition to common diseases such as heart disease or hypertension. Perhaps people are looking in the wrong places and the relevant sequences are in the non-coding regions."
He believes the RNA network provides a new target for interventions, alongside proteomics — the study of the relationship between disease and protein expression.
Professor Mattick said understanding RNA networks would also enable "advanced genetic engineering of plants and animals", which involved manipulation of "the control architecture, not the proteins".
Shattering assumptions about DNA
Scientists have been surprised at the amount of DNA in the human genome that does not code for proteins. Some of this non-coding DNA is present within genes (introns), while other others lie between genes.
"The discovery of the mosaic structure of genes in higher organisms was the biggest surprise in the history of molecular biology. It was swept under the carpet within a few months of being discovered because everybody "knew" that genes coded for proteins. It was rationalised as junk, as an evolutionary hangover," said Professor Mattick.
"This stuff is in all the textbooks. But there was never any evidence for it, it was just a straight assumption."
He set up an alternative hypothesis "that introns are conveying information" and went in search of evidence that would either support it or knock it down.
"I could find nothing that could knock it down. Several things in the textbooks that could theoretically knock it down turned out to be incorrect assumptions," he said.
Professor Mattick reasoned that if these sequences were functional, their only possible function is networking.
"The reason I say that is because they are produced in parallel with protein coding sequences," he said. "If that was the case it also suggested the network was important in the evolution of complexity because this system is highly developed in complex organisms."
He said the proteins that we share with mice and most other animals are relatively stable and it is this control architecture that puts them together in different ways which is evolving.
"What I'm really saying is the system is far more sophisticated than anyone imagined," he said. "When they said there's all this junk in the human genome, it was just stuff they didn't understand."
But is this new level of complexity a reason to be concerned about unforeseen consequences of genetic tinkering?
Professor Mattick thinks not.
"It's a bit like playing around in a clumsy way with processors or control codes of a computer," he said.
"The outcome may be a little unpredictable but it is extremely unlikely that this will lead to a super-computer, or in the case of biology an organism that can out-compete its wild counterparts."
