The University of California, Irvine’s Departments of Chemistry and Physics and Astronomy have discovered new information on a critical enzyme that enables DNA sequencing. The discovery marks a significant step forward in the future of customized medicine, when physicians will be able to construct medicines based specifically on patients’ DNA.
“Enzymes make life possible by catalyzing chemical transformations that otherwise would just take too long for an organism,” said Greg Weiss, UCI professor of chemistry and a co-corresponding author of the new study. “One of the transformations we’re really interested in is essential for all life on the planet – it’s the process by which DNA is copied and repaired.”
The enzyme researched by the UCI-led team is named Taq, after the bacterium in which it was initially found, Thermos aquaticus.
The UCI-led research discovered that Taq, which aids in the replication of DNA, functions in a fundamentally different way than scientists had previously assumed. Weiss stated that instead of acting like a well-oiled, efficient machine constantly churning out DNA copies, the enzyme operates like an indiscriminate consumer cruising the aisles of a store, tossing whatever they see into the shopping basket.
“Instead of carefully selecting each piece to add to the DNA chain, the enzyme grabs dozens of misfits for each piece added successfully,” said Weiss. “Like a shopper checking items off a shopping list, the enzyme tests each part against the DNA sequence it’s trying to replicate.”
Taq is well-known for rejecting any incorrect products that find their way into its virtual shopping cart — rejection is, after all, the key to properly copying a DNA sequence. The frequency with which Taq rejects proper bases is startling in the latest findings. “It’s like a shopper collecting half a dozen identical tomato cans, putting them in the cart, and testing them all when only one can is required.”
According to Philip Collins, a professor in the UCI Department of Physics and Astronomy and a co-corresponding author of the current study, the discovery represents a step toward changing medical treatment. Scientists will be able to better understand how Taq works, they will be able to determine how accurate a person’s sequenced genome is.
“Every single person has a slightly different genome,” said Collins, “with different mutations in different places. Some of those are responsible for diseases, and others are responsible for absolutely nothing. To really get at whether these differences are important or healthcare – for properly prescribing medicines – you need to know the differences accurately.”
Collins, whose team developed the nano-scale equipment for examining Taq’s behavior, stated, “Scientists don’t know how these enzymes achieve their accuracy.” “How do you guarantee a patient that you’ve sequenced their DNA accurately when it differs from the accepted human genome?” “Did the enzyme simply make a mistake, or does the patient have a rare mutation?” Collins wonders.
“This work could be used to develop improved versions of Taq that waste less time while making copies of DNA,” Weiss said.
The research’s implications aren’t limited to medicine; every scientific discipline that relies on precise DNA sequencing will benefit from a deeper knowledge of Taq’s operation.
“We’ve entered the century of genomic data,” said Collins. “At the beginning of the century we unraveled the human genome for the very first time, and we’re starting to understand organisms and species and human history with this newfound information from genomics, but that genomic information is only useful if it’s accurate.”
Scientists rely on assumptions about how DNA changes through time when interpreting evolutionary histories using ancient DNA, for example, and these assumptions are based on reliable genetic sequencing.