By measuring the rate of protein production in bacteria, the team discovered that slight genetic alterations could have a dramatic effect. This was true even for seemingly insignificant genetic changes known as "silent mutations," which swap out a single DNA letter without changing the ultimate gene product. To their surprise, the scientists found these changes can slow the protein production process to one-tenth of its normal speed or less.

As described today in the journal Nature, the speed change is caused by information contained in what are known as redundant codons small pieces of DNA that form part of the genetic code. They were called "redundant" because they were previously thought to contain duplicative rather than unique instructions.

This new discovery challenges half a century of fundamental assumptions in biology. It may also help speed up the industrial production of proteins, which is crucial for making biofuels and biological drugs used to treat many common diseases, ranging from diabetes to cancer.

"The genetic code has been thought to be redundant, but redundant codons are clearly not identical," said Jonathan Weissman, PhD, a Howard Hughes Medical Institute Investigator in the UCSF School of Medicine Department of Cellular andMolecular Pharmacology.

"We didn't understand much about the rules," he added, but the new work suggests nature selects among redundant codons based on genetic speed as well as genetic meaning.

Similarly, a person texting a message to a friend might opt to type, "NP" instead of "No problem." They both mean the same thing, but one is faster to thumb than the other.

How Ribosome Profiling Works

The work addresses an observation scientists have long made that the process protein synthesis, so essential to all living organisms on Earth, is not smooth and uniform, but rather proceeds in fits and starts. Some unknown mechanism seemed to control the speed with which proteins are made, but nobody knew what it was.

To find out, Weissman and UCSF postdoctoral researcher Gene-Wei Li, PhD, drew upon a broader past effort by Weissman and his colleagues to develop a novel laboratory technique called "ribosome profiling," which allows scientists to examine universally which genes are active in a cell and how fast they are being translated into proteins.

Ribosome profiling takes account of gene activity by pilfering from a cell all the molecular machines known as ribosomes. Typical bacterial cells are filled with hundreds of thousands of these ribosomes, and human cells have even more. They play a key role in life by translating genetic messages into proteins. Isolating them and pulling out all their genetic material allows scientists to see what proteins a cell is making and where they are in the process.

See the article here:
Researchers discover new layer of genetic information that helps determine how fast proteins are produced

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