Amazingly, we
may pull this off. This is the key step
toward basic replication of RNA in a cell environment. This could all happen in primordial
environments. Add in the zeolitic
environment of active volcanoes and we have the appropriate witches brew quite
able to facilitate the emergence of replicating basic cells.
We are now a lot
closer today than even ten years ago.
The problem has attracted interest and we really want to see just how
easy and natural the emergence of a primordial cell happens to be. It how looks quite possible.
From there of
course we can run experiments that map cellular evolution. One gets the sense that there are many
pathways but all pathways are essentially channeled. That will also need to be understood.
Synthetic primordial
cell copies RNA for the first time
For the first time, genetic information has been
copied inside a simple cell designed to mimic primordial life. Until now, such
copying had the unfortunate side effect of destroying the cell, but researchers
have found that the cell can be stabilised by adding a dash of citrate. The
substance is synthesised from citric acid, a chemical found in lemons and
oranges.
"We've found a solution to a long-standing
problem in the origin of cellular life," says Jack
Szostak of the
Massachusetts General Hospital in Boston.
The work is part of an ongoing project that aims to
figure out how the first life on Earth formed from a collection of lifeless
molecules. To reconstruct what happened, Szostak and his team have been
experimenting with simple "protocells", essentially bubbles of
fatty acids. These protocells are crude versions of the cells that make up
all modern organisms. Despite lacking any of the complex cellular machinery,
they can reproduce by dividing to form daughter protocells. "What's missing is a replicating genetic
material," Szostak says.
The first life on Earth probably used RNA instead of DNA to carry its genes. It is a simpler molecule
and can perform a host of other functions that would have been helpful to the
first organisms. Szostak has already persuaded his protocells to carry a cargo of RNA. The next step is to get that RNA to copy itself.
That way, when the protocell divides, each daughter cell can be endowed with
copies of all the genetic material.
Stop the destruction
RNA molecules make copies of themselves from a mix
of smaller molecules called nucleotides, each of which is a "letter"
in the genetic code. The nucleotides must come together on the existing RNA,
and hook up.
In the lab, the assembly needs a helping hand from
magnesium ions, or similar charged particles. But by itself that won't work in
Szostak's protocells, because the magnesium ions react with the fatty acids,
tearing the cell to pieces and dumping the newly minted RNA into the
surrounding water where it would rapidly disperse.
With Katarzyna Adamala,
Szostak has now found a way out. They tried adding lots of different chemicals
to the magnesium and protocell cocktail, and eventually found one that
stabilised the cells while still allowing the RNA to copy itself.
The wonder chemical is called citrate, and is easily
produced from citric acid. In the protocells, each citrate molecule clamps
on to a magnesium ion like a hand around a ball, preventing it from
reacting with a fatty acid but still allowing it to interact with the RNA.
"It's a very remarkable observation,"
says Ramanarayanan
Krishnamurthy of the Scripps Research Institute in La Jolla,
California. "This citrate is able to stabilise RNA against degradation,
and also stabilise the protocells against leakage."
If citrate was an essential ingredient for the
formation of the first life then it must have been abundant on Earth 4 billion
years ago. Citrate is found in many modern organisms but it is unclear whether
it could have existed that long ago. However, Krishnamurthy says that similar
molecules certainly did form, and might work just as well. Szostak is also
examining whether small peptides, which are known to bind magnesium ions, might
do the trick. "We haven't found a simple peptide that is as good as citrate
yet, but we are looking," he says.
Primordial Xerox
Szostak's method is crude, and does not use any
enzymes to help the copying along.
He says there is still some way to go before the
system works well enough to sustain living organisms. For example, Szostak
wants the copying to be faster and more accurate.
There is an alternative approach, promoted by Philipp Holliger of
the MRC Laboratory of Molecular Biology in Cambridge, UK. RNA can act as an
enzyme, so Holliger is trying to create an RNA enzyme that can self-replicate,
by accelerating its own natural copying process. He recently built one that could copy strands of RNA longer than itself, a major step towards a self-copying enzyme.
However, Krishnamurthy says that such complex
enzymes probably evolved at a later stage, once RNA-based life was established.
"In the absence of the sophisticated enzymes, citrate could have played
that role," he says.
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