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May 04, 2006
Mobile
DNA Part of Evolution’s Toolbox
The repeated copying of a small
segment of DNA in the genome of a primeval fish may have been
crucial to the transition of ancient animals from sea to land, or
to later key evolutionary changes in land vertebrates. The
discovery is “tantalizing evidence” that copied DNA
elements known as retroposons could be an important source of
evolutionary innovations, says the director of the research,
Howard Hughes Medical Institute investigator David Haussler.
“The big question is
whether this is a special case or whether it's the tip of the
iceberg,” says Haussler, who is at the University of
California, Santa Cruz. A report on the research is published in
the May 4, 2006, issue of the journal Nature.
“The big question is
whether this is a special case or whether it’s the tip of
the iceberg.”
David Haussler
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SCIENTISTS
DISPLAY FISH THOUGHT EXTINCT WITH THE DINOSAURS
Staff
of department of Fish Studies at the National Museum of Kenya
display November 19, 2001 a Coelacanth, caught by Kenyan
fishermen at the coastal town of Malindi in April this year.
There are few species of this deep sea fish which was thought
to have vanished with the dinosaurs 65 milllion years ago.
This particular strain, explained the scientists, gives birth
to young "pups" as opposed to laying eggs.
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Haussler and his colleagues
were led to the discovery through their work on what they call
“ultraconserved elements”—segments of DNA
hundreds of nucleotides long that are almost exactly the same in
a wide variety of vertebrate organisms. Haussler and postdoctoral
fellow Gill Bejerano discovered the ultraconserved elements in
2003, and since then they have been trying to figure out how they
arose and what function they serve.
One ultraconserved element in
particular caught their eye. “We were very interested in
this sequence, because it had a number of copies elsewhere in the
genome,” says Bejerano, who is the first author of the
study. Close copies of the sequence were ubiquitous in
amphibians, birds, and mammals, indicating that it served an
important function. “We found it in every species for which
we have genomes, from frogs to humans,” says Bejerano.
Comparing the sequence to other
species also turned up a big surprise. When the researchers
compared the human ultraconserved element to all the DNA
sequences in the public database GenBank, the closest match was
to DNA from the coelacanth—an ancient fish thought to have
gone extinct millions of years ago until a live specimen was
caught in 1938 off the east coast of South Africa. The coelacanth
is a descendant of the ancient marine organism that gave rise to
the terrestrial vertebrates more than 360 million years ago.
Humans are therefore separated from the coelacanth by hundreds of
millions of years of evolution, yet the two organisms still share
critical DNA sequences.
In the coelacanth, the
ultraconserved segments were produced by a retroposon known as a
short interspersed repetitive element, or SINE, which is a piece
of DNA that can make copies of itself and insert those copies
elsewhere in an organism's genome. Haussler and his colleagues
called this SINE the LF-SINE, where LF stands for lobe-finned
fishes—the group of fishes that gave rise to both the
coelacanth and terrestrial vertebrates.
The LF-SINE was very active in
the evolutionary lineage leading to the terrestrial vertebrates,
but much less active after animals moved onto land. Humans have
245 recognizable copies of the LF-SINE, most or all of which
probably were in place before the origins of the mammals. But in
the lineage leading to the coelacanth, the LF-SINE remained
active, so that the coelacanth genome is now estimated to contain
hundreds of thousands of copies of the sequence.
The close copies of the
ultraconserved element scattered around vertebrate genomes have
changed less than would be expected over evolutionary time,
indicating that they are functionally important. But relatively
few of the copies contain parts that code for proteins, which
suggests they instead are helping to regulate when genes are
turned on and off. Furthermore, when Bejerano analyzed the
locations of the copies, he found that they tended to be near
genes that control the development of the brain.
Haussler and his colleagues
then looked at a particular example—a copy of the
ultraconserved element that is near a gene called Islet 1 (ISL1).
ISL1 produces a protein that helps control the growth and
differentiation of motor neurons. In the laboratory of Edward
Rubin at the University of California, Berkeley, postdoctoral
fellow Nadav Ahituv combined the human version of the LF-SINE
sequence with a “reporter” gene that would produce an
easily recognizable protein if the LF-SINE were serving as its
on-off switch. He then injected the resulting DNA into the nuclei
of fertilized mouse eggs. Eleven days later, he examined the
mouse embryos to see whether and where the reporter gene was
switched on. Sure enough, the gene was active in the embryos'
developing nervous systems, as would be expected if the LF-SINE
copy were regulating the activity of ISL1.
The discoverer of mobile DNA
elements, Barbara McClintock, suggested in 1950 that they might
play a role in the regulation of genes—a hypothesis that
was more fully developed by Roy Britten and Eric Davidson in
about 1970, when it was discovered that more than half of the
human genome consists of remnants of mobile elements. But the
mechanisms underlying this process remained obscure. Haussler's
work provides direct evidence that even when they land at some
distance from a gene, mobile elements like SINEs can be adapted
to serve as regulatory elements that have powerful effects in
their new locations. “When you activate a gene in a new
context,” Bejerano points out, “you get processes
that did not occur before.”
Bejerano and Haussler's results
support the hypothesis that the movement of retroposons can
generate evolutionary experiments by adding new regulatory
modules to genes. Most of these experiments will have no effects
or will harm an organism. But every once in a while, the movement
of a regulatory element will give an organism an evolutionary
advantage. “And to the extent that [such changes] improve
the fitness of an organism,” says Haussler, “they
eventually will become fixed in a population.”
“This suggests a lot of
exciting evolutionary avenues,” says Haussler, “but
we don't yet know how prevalent this kind of evolution is.”
Other labs have found similar examples of mobile elements that
have changed the regulation of genes, and Haussler expects the
number of reports to grow. “It's a very exciting time to be
looking at the human genome, because there's an enormous amount
of DNA that we know is important, but we don't yet know what it's
doing.”
Source
/ Credit: HHMI
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