Fix for 3-billion-year-old genetic error could dramatically improve genetic sequencing

Fix for 3-billion-year-old genetic error could dramatically improve genetic sequencing
Molecular bioscientist Jared Ellefson of the University of Texas at Austin has created a way for RNA to "proofread" copies of genetic information for the first time. This artist's interpretation of the process shows RNA making DNA copies in a droplet of water. Credit: Jared Ellefson, University of Texas at Austin

For 3 billion years, one of the major carriers of information needed for life, RNA, has had a glitch that creates errors when making copies of genetic information. Researchers at The University of Texas at Austin have developed a fix that allows RNA to accurately proofread for the first time. The new discovery, published June 23 in the journal Science, will increase precision in genetic research and could dramatically improve medicine based on a person's genetic makeup.

Certain viruses called retroviruses can cause RNA to make copies of DNA, a process called reverse transcription. This process is notoriously prone to errors because an evolutionary ancestor of all viruses never had the ability to accurately copy genetic material.

The new innovation engineered at UT Austin is an that performs reverse transcription but can also "proofread," or check its work while copying genetic code. The enzyme allows, for the first time, for large amounts of RNA information to be copied with near perfect accuracy.

"We created a new group of enzymes that can read the inside living cells with unprecedented accuracy," says Jared Ellefson, a postdoctoral fellow in UT Austin's Center for Systems and Synthetic Biology. "Overlooked by evolution, our enzyme can correct errors while copying RNA."

Reverse transcription is mainly associated with retroviruses such as HIV. In nature, these viruses' inability to copy DNA accurately may have helped create variety in species over time, contributing to the complexity of life as we know it.

Since discovering reverse transcription, scientists have used it to better understand genetic information related to inheritable diseases and other aspects of human health. Still, the error-prone nature of existing RNA sequencing is a problem for scientists.

"With proofreading, our new enzyme increases precision and fidelity of RNA sequencing," says Ellefson. "Without the ability to faithfully read RNA, we cannot accurately determine the inner workings of cells. These errors can lead to misleading data in the research lab and potential misdiagnosis in the clinical lab."

Ellefson and the team of researchers engineered the new enzyme using directed evolution to train a high-fidelity (proofreading) DNA polymerase to use RNA templates. The new enzyme, called RTX, retains the highly accurate and efficient proofreading function, while copying RNA. Accuracy is improved at least threefold, and it may be up to 10 times as accurate. This new enzyme could enhance the methods used to read RNA from cells.

"As we move towards an age of personalized medicine where everyone's transcripts will be read out almost as easily as taking a pulse, the accuracy of the sequence information will become increasingly important," said Andy Ellington, a professor of molecular biosciences. "The significance of this is that we can now also copy large amounts of RNA information found in modern genomes, in the form of the RNA transcripts that encode almost every aspect of our physiology. This means that diagnoses made based on genomic information are far more likely to be accurate. "


Explore further

Scientists reveal how cell corrects errors made in gene transcription

More information: "Synthetic evolutionary origin of a proofreading reverse transcriptase," Science, DOI: 10.1126/science.aaf5409
Journal information: Science

Citation: Fix for 3-billion-year-old genetic error could dramatically improve genetic sequencing (2016, June 23) retrieved 14 October 2019 from https://phys.org/news/2016-06-billion-year-old-genetic-error-sequencing.html
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Jun 23, 2016
No more evolution? Maybe not a good idea.

Jun 23, 2016
You would want mutation proof coding only for lab grown creations. Immorality would be the end result weather its through the individual, or cloning.

Jun 23, 2016
Well, isn't mutation a cause for cancer?

Jun 23, 2016
No more evolution? Maybe not a good idea.


DNA/protein genetic systems aren't that good (because evolution). I.e. they won't get any better than today, so evolution is safe.

Jun 23, 2016
But they said the creator was perfect!

Jun 23, 2016
But they said the creator was perfect!

Of course he is. This was not a bug, it's a feature.

Jun 24, 2016
Yes kochevnik, the Creator is, indeed, perfect. But mankind is IMPERFECT because he is flesh. If geneticists think they can make improvements, there's no harm in that.
But by the same token, they also could cause mutations where monstrous creatures that are human by species will be born. The internet offers some sites where human freaks of nature are shown. Some conditions are caused by disease and some are caused by a problem with the growth process of the fetus or blastoma. If science can improve the odds for normalcy, then why not? One of my favorites is the two heads on one body. Beautiful twin girls where their two heads look normal, but they share one body. One head is named Abigail. Can't remember the other one. They are now teenagers. While we feel sad for them, at least they were able to live and seem happy, and their parents and siblings love them.

Jun 24, 2016
Ugh, why bait the dumb troll under the bridge? He couldn't even read the article, where it clearly is stated it is a natural mechanism. (As if his magic really existed, but let's humor the eternally stupid ones, they can't help that they szuck.)

Jun 24, 2016
Well, isn't mutation a cause for cancer?

It is. But mutation is also the driver for evolution. So you can't really have one without the other.

In any case this is a mechanism that only works in for lab purposes (making a copy of a sequence for diagnostic purposes). Living creatures have transcription methods that do make errors and you can't just swap those out. This is not applicable to cell replication.
(Also note that they say 'near perfect accuracy' in the article. So there are still some errors)

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