Featured Research

from universities, journals, and other organizations

Silent mutations speak up: Multiple silent mutations greatly impact protein translation

Date:
June 5, 2014
Source:
University of Utah
Summary:
Returning to research of years ago, biologists developed an assay to test effects of all possible silent mutations on protein translation. One-third of silent mutations caused a slow down--in some cases decreasing the speed of translation five-fold.

This is a visual readout of the varied effects of silent mutations in the bacteria, Salmonella enterica.
Credit: Fabienne Chevance

So-called silent DNA mutations earned their title because, according to the fundamental rules of biology, they should be inconsequential. Reported on June 5 in PLOS Genetics online, University of Utah researchers experimentally proved there are frequent exceptions to the rule. The work was conducted in the bacteria, Salmonella enterica, used to study basic biological mechanisms that are often conserved in humans.

Related Articles


"In this post-genomic era, where a patient's DNA sequence can be used to diagnose predisposition to diseases, silent mutations are usually ignored," said senior author Kelly T. Hughes, professor of biology at the University of Utah. "Our data argue that they shouldn't be."

The definition of a silent mutation rests on a fundamental principle in biology. DNA is transcribed into RNA, and RNA is translated into protein. Using an analogy, DNA are letters, and when grouped into three-letter words, they form a code that specifies which protein will be made. A silent mutation is similar to a "c" to "k" change in "the cat ran" and "the kat ran." Despite the alternate spelling, the meaning is the same.

Because Hughes had assumed the dogma on silent mutations to be true, he nearly lost the chance to make an important discovery. Twenty years prior, he had dismissed experimental results implicating a silent mutation as the cause of a severe defect in bacteria.

"We thought there was some other mutation somewhere else that we couldn't find," remarked Hughes. "We didn't realize at the time that we were throwing away gold."

In the years following, evidence started to emerge indicating that silent changes could have serious consequences to bacteria and animals. But the cases were isolated, and it remained to be determined whether they were part of a larger phenomenon.

In light of the new data, Hughes decided to pursue his finding from years ago, but on a broader scale. He developed an assay to test the effects of all possible silent mutations on protein translation in bacteria. The beauty of the system is that it eliminates many of the variables that could be introduced at intermediate steps in the process, meaning any effect on translation should directly link back to the change in DNA.

"I didn't think it would work," said research assistant professor and first author Fabienne Chevance. "I didn't imagine that a single base pair change could have as big of an effect as we saw."

The assay showed that an unexpected one-third of silent mutations caused protein translation to slow down, in some cases decreasing the speed by as much as five-fold. The scientists surmise that just as the alternate spelling in "the kat ran" might cause a reader to hesitate, certain silent mutations causes the ribosomal machinery that carries out translation to balk.

Silent mutations weren't the only types of DNA changes to effect translation efficiency. It turns out that for the words in the sentence -- called codons -- what your neighbors are matters. For example, "the cat ran" could be read faster than "the ran cat." The phenomenon, dubbed "codon context," changed the speed of translation by up to 30-fold.

The implications are that similar changes within any protein coding region could alter the amount of protein made, ultimately impacting the fitness of the organism.

The conclusions fit well with observations from population biologists, who found that specific silent mutations and codon contexts are statistically underrepresented in protein coding regions in many organisms, suggesting those codes could be detrimental. The results from Chevance and Hughes explain the biology behind the statistics and represent the first systematic validation of the phenomena in a living organism in real time.

"We've been able to experimentally prove what population geneticists have believed for decades," said Hughes. "Every DNA base can matter."

The research was funded by NIH PHS grant GM062206.


Story Source:

The above story is based on materials provided by University of Utah. Note: Materials may be edited for content and length.


Journal Reference:

  1. Fabienne F. V. Chevance, Soazig Le Guyon, Kelly T. Hughes. The Effects of Codon Context on In Vivo Translation Speed. PLoS Genetics, 2014; 10 (6): e1004392 DOI: 10.1371/journal.pgen.1004392

Cite This Page:

University of Utah. "Silent mutations speak up: Multiple silent mutations greatly impact protein translation." ScienceDaily. ScienceDaily, 5 June 2014. <www.sciencedaily.com/releases/2014/06/140605190700.htm>.
University of Utah. (2014, June 5). Silent mutations speak up: Multiple silent mutations greatly impact protein translation. ScienceDaily. Retrieved November 27, 2014 from www.sciencedaily.com/releases/2014/06/140605190700.htm
University of Utah. "Silent mutations speak up: Multiple silent mutations greatly impact protein translation." ScienceDaily. www.sciencedaily.com/releases/2014/06/140605190700.htm (accessed November 27, 2014).

Share This


More From ScienceDaily



More Plants & Animals News

Thursday, November 27, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Classic Hollywood Memorabilia Goes Under the Hammer

Classic Hollywood Memorabilia Goes Under the Hammer

Reuters - Entertainment Video Online (Nov. 26, 2014) The iconic piano from "Casablanca" and the Cowardly Lion suit from "The Wizard of Oz" fetch millions at auction. Sara Hemrajani reports. Video provided by Reuters
Powered by NewsLook.com
Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

Newsy (Nov. 25, 2014) The US FDA is announcing new calorie rules on Tuesday that will require everywhere from theaters to vending machines to include calorie counts. Video provided by Newsy
Powered by NewsLook.com
Feast Your Eyes: Lamb Chop Sent Into Space from UK

Feast Your Eyes: Lamb Chop Sent Into Space from UK

Reuters - Light News Video Online (Nov. 25, 2014) Take a stab at this -- stunt video shows a lamb chop's journey from an east London restaurant over 30 kilometers into space. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins