GAINESVILLE, Fla. (Feb. 20, 2004) - A team of University of
Florida scientists has developed an artificial chemical system that for the
first time can mimic the natural evolutionary process living organisms undergo.
Specifically, the team showed that an artificially created
DNA-like molecule containing six gene-building nucleotides - instead of the
four found in natural DNA - could support the molecular "photocopying"
operation known as polymerase chain reaction. The artificial DNA-like molecule
directed the synthesis of copies of itself and then copies of the copies,
mimicking the natural process of evolution as it was first outlined by Charles
Darwin. A nucleotide is a building block of DNA, or a "letter" in the genetic
alphabet used to write the "book" describing our genetic inheritance.
"The potential implications of this in diagnosis and medicine
are clear," said Steven Benner, a UF distinguished professor of chemistry and
anatomy and cell biology and the lead researcher on the study. "This technology
will enhance our ability to detect unwanted genetic material from viruses,
bacteria and even biological warfare agents. It will also streamline our
ability to detect defects in natural DNA, such as those responsible for cancers
and genetic diseases."
The announcement, which appeared in February in the journal
Nucleic Acids Research, provides a key step toward developing an artificial
form of life. Scientists have been attempting to get artificial chemical
systems that support Darwinian evolution for a decade.
Benner, a member of the UF Genetics Institute, and Michael
Sismour, a UF graduate student, built on work done by James Watson and Francis
Crick, the Nobel Prize winners who proposed 50 years ago the DNA double helix.
Watson and Crick showed that four nucleotides encoded information in the DNA
molecule, writing our genetic instructions as a string of letters - G, A, T and
C, representing guanine, adenine, thymine and cytosine. These letters form the
famous Watson-Crick base pair that holds together the two strands of the double
helix. This pairing follows simple rules: A from one strand pairs with T from
the other, while G from one strand pairs with C from the other.
A decade ago, at the Swiss Federal Institute of Technology,
Benner's group showed it was possible to increase the number of nucleotides
from four to 12. More turns out to be better in the case of DNA. By adding
extra nucleotides the number of pairing rules increase, Benner said. "This
increases the ways that DNA can come together, giving the biotechnologist
enormously enhanced control over how DNA strands assemble."
This increased control has enabled commercially successful
diagnostic assays. Today in the clinic, patients infected with HIV and
hepatitis C have the load of viruses in their body monitored by diagnostic
tools that exploit Benner's extra nucleotides. That helps doctors better
predict when resistant strains of the virus are likely to emerge in the
patient.
"Our artificial DNA has widespread benefit for patients in
diagnostics," Benner said. "But until now, it has been largely passive. It has
not been able to copy itself."
In order to create a DNA-like molecule able to reproduce
itself, the researchers had to find an enzyme, known as a DNA polymerase, that
would hold the GATC building blocks of natural DNA in the positions necessary
to create the famous Watson-Crick base pair. They then assembled the correctly
paired nucleotides into a strand.
Adding a fifth and sixth nucleotide was not difficult from a
chemical perspective. But it was difficult to find a DNA polymerase to accept
the unnatural nucleotides, Benner said.
"DNA polymerases have evolved for billions of years to accept
the four natural letters in DNA - A, T, C, and G." Benner said. "Coaxing them
to accept two new letters, like K and X, was difficult."
Benner turned to a new technology called "protein
engineering," to develop an altered DNA polymerase that would work. Using the
changed polymerase, the team was able to "evolve" their artificial DNA through
five generations.
As it happens, the
UF group's work was anticipated by science fiction. In an episode of the popular
TV show the "X-files," one of the characters finds in a virus a fifth and sixth
DNA nucleotide - a new base pair - stating: "What you are looking at exists
nowhere in nature. It would have to be, by definition, extraterrestrial,"
Or in Benner's lab, it seems.
"Considering how hard we had to work to get Earth polymerases
to accept our artificial DNA, we doubt that our artificial DNA would survive
for an instant outside of the laboratory on this planet. But a six-letter DNA
might support life on other planets, where life started with six letters and is
familiar with them. Or even DNA that contains up to 12 letters, which we have
shown is possible."
"This is quite a breakthrough," said Christopher Switzer, who
began this work in Benner's laboratory in Switzerland over a decade ago and is
now chairman of the department of chemistry at the University of California,
Riverside.
"The news is highly exciting", said Joseph Piccirilli, who
also began research in this area, and who is now a member of the Howard Hughes
Medical Institute at the University of Chicago. "It opens up a new direction at
the interface between chemistry and biology."
Source: Steven Benner,
352-392-7773, benner@chem.ufl.edu
Or contact News & Public Affairs, 352-392-0186, newsdesk@ufl.edu