Scientists make leap forward for genetic sequencing
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 Department of Chemistry at the University of California, Irvine, and the Department of Physics and Astronomy at the University of California, Irvine, published a paper today in Sciences Advances that revealed new details about a key enzyme that makes DNA sequencing possible. It is a leap forward into the era of personalized medicine when doctors will be able to design treatments based on the genomes of individual patients.

"Enzymes make life possible by catalyzing chemical transformations that otherwise would just take too long for an organisms," said Greg Weiss, UCI professor of chemistry and a co-corresponding author of the new study.

The molecule the UCI-led team studied is called Taq, a name derived from the microorganism it was first discovered in. The molecule the UCI-led team studied is called Taq, a name derived from the microorganism it was first discovered in. Taq is capable of replicating DNA. The technique with thousands of uses from forensics to PCR tests to detect COVID-19 takes advantage of Taq.

The team found that Taq behaves differently than scientists had thought. Weiss explained that the enzyme acts like an indiscriminate shopper, throwing everything they see into the shopping cart, instead of behaving like a well-oiled, efficient machine.

Weiss said that instead of carefully selecting each piece to add to the DNA chain, the enzyme grabs dozens of misfits for each piece added successfully.

It is well-known that Taq rejects any wrong items that land in its shopping cart, and that rejection is the key to successfully duplicating a DNA sequence. The new work shows how frequently Taq rejects correct bases.

Taq is less efficient at doing its job than it could be.

Philip Collins, a professor in the UCI Department of Physics and Astronomy, is a co-corresponding author of the new research. Scientists can better understand how accurate a person's genome truly is if they understand how Taq functions.

Collins said that every single person has a slightly different genome. Some of them are responsible for diseases and some of them are not. You need to know the differences accurately to get at whether these differences are important or healthcare.

Collins said that scientists don't know how these enzymes achieve their accuracy. Does the patient really have a rare abnormality, or was it just a mistake?

Weiss said that the work could be used to develop improved versions of Taq that waste less time while making copies of DNA.

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, scientists rely on assumptions about how DNA changes over time, and those assumptions rely on accurate genetic sequencing.

Collins said that we have entered the century of genomic data.

The co-authors of this study are a former graduate student in physics and astronomy and a former graduate student in biology.

More information: Mackenzie W. Turvey et al, Single-molecule Taq DNA polymerase dynamics, Science Advances (2022). DOI: 10.1126/sciadv.abl3522 Journal information: Science Advances Citation: Scientists make leap forward for genetic sequencing (2022, March 11) retrieved 11 March 2022 from https://phys.org/news/2022-03-scientists-genetic-sequencing.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.