IN AN attempt to go one better than nature, researchers in California are
expanding the genetic code that has given rise to just about every form of life.
They hope to create artificial DNA capable of producing proteins no one has ever
seen before.
Apart from RNA viruses, all organisms carry their genetic information in
strings of DNA built from the same 4 bases, adenine, which pairs with thymine,
and cytosine, which pairs with guanine. These bases are grouped in units of
three called codons, and each codon adds one of 20 naturally occurring amino
acids to protein chains.
Researchers at the Scripps Research Institute in La Jolla, California, led by
Floyd Romesberg have succeeded in adding new players to the original cast of
four DNA bases, increasing the number of ways bases can pair up to produce new
codons. These in turn should make artificial amino acids and hence new proteins,
they say.
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Researchers have experimented with unnatural bases since the 1980s, but no
one has been able to incorporate them into DNA without making it unstable. Now
Romesberg鈥檚 and his colleagues have overcome these barriers. They have made 20
unnatural bases which, like natural bases, link with sugars to form nucleosides.
鈥淭he biggest surprise was there鈥檚 nothing special about a [natural base],鈥� says
Romesberg.
The group then inserted one of these artificial bases into single strands of
DNA. During DNA replication, enzymes called polymerases read single-strand
templates and then add appropriate bases to form pairs鈥攁denine to thymine,
cytosine to guanine and vice versa. An unnatural base has a different shape and
binds differently, and in early experiments the team found that several
polymerases would add unnatural partners to such bases. The problem was that
replication then stopped.
To overcome this, the group tested different polymerases and unnatural bases
until they found a combination that worked without shutting the system down.
They have now successfully replicated DNA strands beyond the formation of the
unnatural pair. The process remains slow, because the researchers are working by
trial and error.
The team鈥檚 ultimate goal is to insert the artificial DNA into bacteria and
get the new codons read without disrupting normal cellular operations. 鈥淭hat is
not an easy project,鈥� says Eric Kool, a chemist at Stanford University in Palo
Alto, California. But if successful, bacteria could produce completely unnatural
proteins for use in medicine or chemistry.