IT'S not often that the audience at a scientific meeting gasps in amazement during a talk. But that's what happened recently when researchers revealed that they had deleted huge chunks of the genome of mice without it making any discernable difference to the animals.
The result is totally unexpected because the deleted sequences included so-called "conserved regions" thought to have important functions. All DNA tends to acquire random mutations, but if these occur in a region that has an important function, individuals will not survive.
Key sequences should thus remain virtually unchanged, even between species. So by comparing the genomes of different species and looking for regions that are conserved, geneticists hope to pick out those that have an important function.
It was assumed that most conserved sequences would consist of genes coding for proteins. But an unexpected finding when the human and mouse genomes were compared was that there are actually more conserved sequences within the deserts of junk DNA, which does not code for proteins.
The thinking has been that these conserved, non-coding sequences must, like genes, be there for a reason. And indeed, one group has shown that some conserved regions seem to affect the expression of nearby genes.
To find out the function of some of these highly conserved non-protein-coding regions in mammals, Edward Rubin's team at the Lawrence Berkeley National Laboratory in California deleted two huge regions of junk DNA from mice containing nearly 1000 highly conserved sequences shared between human and mice.
One of the chunks was 1.6 million DNA bases long, the other one was over 800,000 bases long. The researchers expected the mice to exhibit various problems as a result of the deletions.
Yet the mice were virtually indistinguishable from normal mice in every characteristic they measured, including growth, metabolic functions, lifespan and overall development.
"We were quite amazed," says Rubin, who presented the findings at a recent meeting of the Cold Spring Harbor Laboratory in New York. He thinks it is pretty clear that these sequences have no major role in growth and development.
"There has been a circular argument that if it's conserved it has activity." Another possibility, as Rubin acknowledges, is that these regions serve a purpose too subtle to be seen in the tests done on mice. "It may say as much about our inability to detect any phenotypes as it says about the function of this region," says David Haussler of the University of California, Santa Cruz, who thinks the work of Rubin's team is impressive and significant.
"My sense is they do have confer some kind of advantage." There might be a third explanation: similar regions on other chromosomes could make up for the deletions. "It could be that these elements are so critical that there is redundancy in the system," says Kelly Frazer of Perlegen Sciences in California.
Whatever the reason, it's becoming clear that there are different kinds of conserved DNA and that some will turn out to be more important than others, says Rubin. Haussler's team recently described "ultra-conserved regions" in mammals.
The level of conservation was even higher than that for many genes. "What's most mysterious is that we don't know any molecular mechanism that would demand conservation like this," Haussler says.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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