'Junk' DNA reveals vital role - discovery just 'tip of the iceberg' (11/5/2004)

It was supposed to be redundant genetic rubbish but now it turns out "junk" DNA plays a "vital role".

Dr Michael Antoniou points out that here we have yet more evidence as to how little we know about the structure and function of the genome. It is also more reason why we shouldn't venture down the GM route since we haven't got a clue about what we may be interfering with.

According to geneticist Kerstin Lindblad-Toh of the Broad Institute in Cambridge, Massachusetts, quoted in the article below, "This is the tip of the iceberg" in terms of our igorance.

'Junk' DNA reveals vital role
Inscrutable genetic sequences seem indispensable.
Nature Science Update, 7 May 2004

If you thought we had explored all the important parts of our genome, think again. Scientists are puzzling over a collection of mystery DNA segments that seem to be essential to the survival of virtually all vertebrates. But their function is completely unknown.

The segments, dubbed 'ultraconserved elements', lie in the large parts of the genome that do not code for any protein. Their presence adds to growing evidence that the importance of these areas, often dismissed as junk DNA, could be much more fundamental than anyone suspected.

David Haussler of the University of California, Santa Cruz, and his team scanned the genome sequences of man, mouse and rat1. They found more than 480 ultraconserved regions that are completely identical across the three species. That is a surprising similarity: gene sequences in mouse and man for example are on average only 85% similar. "It absolutely knocked me off my chair," says Haussler.

The regions largely match up with chicken, dog and fish sequences too, but are absent from sea squirt and fruitflies. The fact that the sections have changed so little in the 400 million years of evolution since fish and humans shared a common ancestor implies that they are essential to the descendants of these organisms. But researchers are scratching their heads over what the sequences actually do.

The most likely scenario is that they control the activity of indispensable genes. Nearly a quarter of the sequences overlap with genes and may be converted into RNA, the intermediate molecule that codes for protein. The sequences may help slice and splice RNA into different forms, Haussler suggests.

Another set may control embryo growth, which follows a remarkably similar course in animals ranging from fish to humans. One previously identified ultraconserved element, for example, is known to direct a gene involved in the growth of the brain and limbs.

To solve the conundrum, experts predict a flurry of studies into the enigmatic DNA chunks. "People will be intrigued by this [finding]," says Kelly Frazer who studies genomics at Perlegen Sciences in Mountain View, California. "It is the kind of stuff that blows people away."

Hard to believe

Geneticists have known for some years that there are critical sections of DNA aside from the much-acclaimed genes. A fair fraction of the mouse and human genomes, aside from protein-coding sequences, show strong similarities.

But ultraconserved segments are particularly unusual because they are 100% identical in man and mouse. Until now, some thought they were human DNA that had contaminated mouse samples. "People had a hard time believing it," Frazer says.

The presence of exact copies in different animals suggests that even tiny changes in the sequence of these segments destroy whatever they do, and have been weeded out during evolution. Non-essential regions of DNA, by contrast, tend to accumulate mutations so that the sequences vary in different organisms.

Figuring out what the mystery segments do will be difficult.

There are few similarities between one region and another, so these cannot be used to provide clues to their function. One laborious technique will be to genetically engineer mice that lack one segment and see how that affects their growth and behaviour.

Once the function of ultraconserved elements is resolved, researchers will still have to tackle other vast tracts of the genome that are similar in different organisms, says geneticist Kerstin Lindblad-Toh of the Broad Institute in Cambridge, Massachusetts. "This is the tip of the iceberg," she says.


1. Bejerano, G. et al. Science, published online, doi:10.1126/science.1098119, (2004).

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