HELEN PEARSON
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.
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