Leap Forward in Genetic Sequencing Will Lead to Improved Personalized Medicine and Understanding of Evolution

Leap Forward in Genetic Sequencing Will Lead to Improved Personalized Medicine and Understanding of Evolution

In a paper published on March 11, 2022, in Sciences Advances, researchers in the Department of Chemistry and the Department of Physics & Astronomy at the University of California, Irvine revealed new details about a key enzyme that makes

This image shows the Taq enzyme in its open configuration waiting for a new chemical base to arrive so it can try to fit it to a DNA chain. Credit: Max Strul / UCI and Lorena Beese laboratory / Duke University

The molecule the UCI-led team studied is an enzyme called Taq, a name derived from the microorganism it was first discovered in, Thermos aquaticus. The molecule the UCI-led team studied is an enzyme called Taq, a name derived from the microorganism it was first discovered in, Thermos aquaticus. Taq replicates DNA. Polymerase chain reaction, the technique with thousands of uses from forensics to PCR tests to detect

It’s well-known that Taq rejects any wrong items that land into its proverbial shopping cart – that rejection is the key, after all, to successfully duplicating a DNA sequence. What’s surprising in the new work is just how frequently Taq rejects correct bases. “It’s the equivalent of a shopper grabbing half a dozen identical cans of tomatoes, putting them in the cart, and testing all of them when only one can is needed.”

The take-home message: Taq is much, much less efficient at doing its job than it could be.

The find is a leap toward revolutionizing medical care, explained Philip Collins, a professor in the UCI Department of Physics & Astronomy who’s a co-corresponding author of the new research. That’s because if scientists understand how Taq functions, then they can better understand just how accurate a person’s sequenced genome truly 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.”

“Scientists don’t know how these enzymes achieve their

The impacts of the work don’t stop at medicine; every scientific field that relies on accurate DNA sequencing stands to benefit from a better understanding of how Taq works. In interpreting evolutionary histories using ancient DNA, for example, scientists rely on assumptions about how DNA changes over time, and those assumptions rely on accurate genetic sequencing.

“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.”

Reference: “Single-molecule Taq DNA polymerase dynamics” by Mackenzie W. Turvey, Kristin N. Gabriel, Wonbae Lee, Jeffrey J. Taulbee, Joshua K. Kim, Silu Chen, Calvin J. Lau, Rebecca E. Kattan, Jenifer T. Pham, Sudipta Majumdar, Davil Garcia, Gregory A. Weiss and Philip G. Collins, 11 March 2022, Science Advances.


DOI: 10.1126/sciadv.abl3522

Co-authors on this study include Mackenzie Turvey, Ph.D., a former UCI graduate student in physics & astronomy, and Kristin Gabriel, Ph.D., a former UCI graduate student in molecular biology & biochemistry. This research was funded by the National Human Genome Research Institute of the NIH.

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Author: admin