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arabinose in ANA, the ringed structure
anhydrohexitol in HNA, and threose, a
four-carbon sugar in TNA. The scientists
also created XNA molecules called FANA
( 2’-fluoroarabinose), CeNA (
cyclohex-ene) and LNA (“locked” ribose analog).
Researchers led by Philipp Holliger
of the MRC Laboratory
of Molecular Biology
in Cambridge, England
synthesized the six molecules — four of them
for the first time—and
created special enzymes
for all six XNAs so that they
could evolve.
The enzymes could
“read” the order of molecular components in a strand
of XNA and use that information to build a complementary strand of DNA. Working with
an enzyme from a sulfur-loving microbe,
the team selected for versions of the
enzyme that could read each of the XNAs.
The researchers also made enzymes that
could do the reverse: Read DNA and use
that information to build XNA.
Because the XNAs can’t copy themselves without help from DNA, it’s not
truly synthetic life, says Joyce. But the
molecules do undergo good old-fashioned evolution. With HNA, for example,
the researchers created a random population of HNA molecules, then exposed
them to a bunch of target molecules (such
as proteins or RNA) for the HNA to attach
to. Most of the HNAs didn’t do diddly-squat, but a fraction were slightly better
at connecting to the target molecules.
Scientists selected the handful of
HNAs that did show some affinity for
the targets and replicated those with
the help of DNA. After several gen-
erations of such HNA selecting and
copying, the researchers had a group of
HNAs that were pretty good at attaching
to their targets.
“Thus, heredity and evolution, two
hallmarks of life, are not limited to DNA
and RNA but are likely to be emergent
properties of polymers capable of infor-
mation storage,” the researchers write.
TNA, which has been previously syn-
thesized using ordinary enzymes, is
especially intriguing to scientists. Earlier
work showed that TNA can pair up with
DNA and RNA, and TNA’s four-carbon
sugar threose is a simpler
molecule than the five-
carbon sugars found in
DNA and RNA. Simple is
good when speculating
about what the first mol-
ecules of life might have
looked like, says Joyce.
“TNA has the right look
and feel of something that
might come first,” he says.
Because ordinary en-
zymes that snip and
degrade things in the body
shouldn’t recognize the XNAs, the mole-
cules should be very stable — in fact some
are just more stable to begin with due
to their chemistry, says coauthor Vitor
Pinheiro, also from the MRC Laboratory.
After incubating HNA in an extremely
acidic solution for an hour, for example,
the molecule was fine. “DNA just would
have been shredded,” says Pinheiro.
This stability suggests the XNAs have
great potential as biotechnology and
materials science tools. RNA and DNA
are used in vaccines and drugs but often
have to be modified to be made more
durable. And because the XNA mole-
cules can evolve, researchers can select
for traits they want in a particular XNA
and then direct its evolution.
Steven Benner of the Foundation for
Applied Molecular Evolution in Gaines-
ville, Fla., says the work is not only rel-
evant to biotechnology here on Earth,
but also “for the possible forms that life
might take throughout the cosmos.” s
“Maybe we’ll
find evidence
of some kind of
life on Europa
or fossilized life
on Mars. Or
maybe we’ll just
make it. That’s
my bet.”
GERALD JOYCE
Synthetic genetic molecules can
store info, pass it on — and evolve
By Rachel Ehrenberg
By swapping out the sugars that put the
D in DNA and creating designer enzymes
to read these molecules, scientists have
made new hereditary molecules that can
undergo Darwinian evolution.
Getting the six new molecules, collectively called XNAs, to replicate is a major
technological advance that could lead to
all sorts of new drugs, sensors and diagnostic devices. The research, reported in
the April 20 Science, could also provide
clues to how life evolved on Earth.
“What makes DNA and RNA so cool is
they are the genetic molecules, they are
the basis for propagating information
through generations,” says biochemist
Gerald Joyce of the Scripps Research
Institute in La Jolla, Calif. “Well, we now
have eight genetic molecules: RNA, DNA
and these six.”
While just creating the XNAs (short
for xenonucleic acids) represents a feat
in itself, the molecules can’t do the entire
evolution thing on their own: DNA still
lends a hand at the replication stage. But
the work is a step toward envisioning an
alternative kind of life and as such is “a
wonderful achievement,” says Joyce,
author of a commentary on the work in
the same issue of Science.
“We only know this one example of
life — it’s what’s been on Earth for 4 bil-
lion years,” he says. “Maybe we’ll find
evidence of some kind of life on Europa
[a moon of Jupiter] or fossilized life
on Mars. Or maybe we’ll just make it.
That’s my bet.”
In the backbone of every DNA mole-
cule there are repeating units of deoxy-
ribose sugar; in the RNA backbone, it’s
ribose sugar. Instead of those sugars,
each XNA has a different molecule in
its backbone: A five-carbon sugar called
