Scientists Reverse Evolution, Reconstruct Ancient
Gene
By
Ker
Than
LiveScience Staff Writer
It's not Jurassic Park, but scientists have reconstructed
a 530-million-year-old gene by piecing together
key portions of two modern genes descended from
it.
"We've shown some of the elements involved
in the process of evolution
by reversing this process and reconstructing a
gene that later became two genes," said study
team member Mario Capecchi of the University of
Utah School of Medicine.
The achievement, detailed in the Aug. 7 issue
of the journal Developmental Cell, could lead
to new types of gene therapy, in which a damaged
gene could be restored by pairing parts of it
with portions from a similar gene from another
part of the body, the researcher say.
NoSplitting up the job
Genes are snippets of DNA
that carry instructions for building a protein.
The splitting of one gene
into many genes has occurred many times throughout
life's
history.
With two identical genes, one can continue doing
its normal job while the other is free to mutate.
Most mutations are harmful and disappear, but
every once in a while one proves beneficial
to the organism and is passed on to future generations.
The researchers reconstructed an ancient control
gene, called "Hox," which directs the
actions of other genes during development of an
animal embryo.
Early animals had 13 Hox genes until about 500
million years ago. Those 13 Hox genes multiplied
four times, but some were lost because they were
redundant. Today, humans and other mammals have
39 Hox genes.
The modern descendent of one of those archaic
genes, Hox1, are Hoxa1 and Hoxb1.
Hoxa1 is important for breathing
functions. When Hoxa1 is disabled in embryonic
mice, they die shortly after birth. Hoxb1 orders
the formation of nerve cells that ultimately control
facial expressions in animals. When a
mouse is born
with a disabled Hoxb1 gene, it suffers facial
paralysis and can't blink its eyes, wiggle its
whiskers or pull back its ears.
The researchers combined critical portions of
Hoxa1 and Hoxb1 to recreate the original Hox1.
The reconstructed gene performed the jobs of both
genes. Mice born with Hox1 could breathe because
they had the crucial part of Hoxa1, and they could
move their facial muscles because they had a small
bit of Hoxb1.
"What we have done is essentially go back
in time to when Hox1 did what Hoxa1 and Hoxb1
do today," Capecchi said.
|
At
top and bottom left are two mice that have
disabled copies of Hoxb1, a gene that controls
the nerves needed for facial expressions.
When a puff of air was blown into the face
of the first mouse (top right), it couldn't
blinke, wiggle its ears or pull back its ears.
The mouse that had a piece of Hoxb1 combined
with Hoxa1, however, could react, thanks to
the reconstructed gene.
Credit: Petr Tvrdik/University of Utah |
Gene
substitutions
The new hybrid gene is not an exact copy of the
530-million-year-old gene, the researcher say,
but it does perform essentially all the functions
of the ancient gene. The reconstructed gene lacks
Hoxc1 and Hoxd1, two descendent genes that vanished
during evolution
because they were either redundant or played minor
roles.
The study could lead to new approaches to gene
therapy, the researchers say.
"It shows that genes are not as different
as we thought, and that we can perhaps tweak and
recruit one to do the job of another that is mutated
and not as easy to fix," study team member
Petr Tvrdik told LiveScience.
If a gene duplicated into two and evolved separate
functions in the body-for example, one gene works
in the brain and the other in the liver-then if
the brain
version of the gene becomes mutated or deleted,
parts of it could be combined with portions of
the liver gene to reconstruct a gene similar to
the normal brain gene.
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