Featured Research

from universities, journals, and other organizations

Biologists Discover How 'Silent' Mutations Influence Protein Production

Date:
April 10, 2009
Source:
University of Pennsylvania
Summary:
Biologists have revealed a hidden code that determines the expression level of a gene, providing a way to distinguish efficient genes from inefficient ones. The research involved creating hundreds of synthetic green-glowing genes and provides an explanation for how a cell "knows" how much of each protein to make.

This is a 96-well plate containing the bacteria expressing different synonymous versions of the GFP gene.
Credit: Josh Plotkin and the University of Pennsylvania

Biologists at the University of Pennsylvania have revealed a hidden code that determines the expression level of a gene, providing a way to distinguish efficient genes from inefficient ones. The new research, which involved creating hundreds of synthetic green-glowing genes, provides an explanation for how a cell "knows" how much of each protein to make, providing just the right amount of protein to maintain homeostasis yet not too much to cause cell toxicity.

Related Articles


In the study, Penn biologists analyzed how protein levels are governed by synonymous, or silent, mutations within the protein-coding region.

Synonymous mutations do not change the amino-acid sequence of a protein, but they can nevertheless influence the amount of the protein that is produced. The researchers identified the mechanism underlying this regulation: synonymous mutations determine mRNA folding and thereby the eventual protein level. The researchers also identified a class of mutations that did not directly affect protein levels but slowed bacterial growth.

For biologists, these results fundamentally change the understanding of the role of synonymous mutations, which were previously considered evolutionarily neutral. The findings may also improve the design of therapeutic genes. Many drugs, such as insulin, are produced by transgenic cell lines. Using optimized genes will produce larger amounts of therapeutic proteins while keeping the transgenic, carrier cells healthy and fast-growing.

The human genome contains more than 20,000 genes that encode the proteins present in a human body. Some of these proteins are needed in bulk, while for others a tiny amount is sufficient and a large amount would be toxic. The question is how cells "know" how much of each protein to make.

To answer this question, Joshua B. Plotkin, senior author and the Martin Meyerson Assistant Professor in the Department of Biology in Penn's School of Arts and Sciences, and colleagues at Harvard University and the University of Edinburgh engineered a synthetic library of 154 genes that varied randomly at synonymous sites. All the genes encoded the same green fluorescent protein, enabling the researchers to easily study the effects of such mutations on protein levels when expressed in the bacterium Escherichia coli.

The silent mutations changed the amount of fluorescent protein by as much as 250-fold, without changing the properties of the protein. Codon bias, the probability that one codon of three adjacent nucleotides will code for one amino acid over another, was previously thought to be the cause for protein expression variance, but it did not correlate with gene expression in these experiments.

"At first we were stumped," Plotkin said. "How were the silent mutations influencing protein levels? Eventually, we looked at mRNA structure and discovered that this was the underlying mechanism."

The stability of mRNA folding near the ribosomal binding site explained more than half the variation in protein levels. To understand this observation, the researchers simulated the spatial arrangement of the messenger RNA molecule that carries the information from genes to proteins. They found that the inefficient genes produced tightly folded mRNA molecules that could not be accessed by the protein-making machinery. According to their analysis, mRNA folding and associated rates of translation initiation play a predominant role in shaping expression levels of individual genes, whereas codon bias influences global translation efficiency and cellular fitness.

The study, appearing in the current issue of the journal Science, was performed by Plotkin, as well as first author Grzegorz Kudla of the Department of Biology at Penn, Andrew W. Murray of the Department of Molecular and Cellular Biology at Harvard and David Tollervey of the Wellcome Trust Centre for Cell Biology at Edinburgh.

The study was funded by the Burroughs Wellcome Fund, James S. McDonnell Foundation, Penn Genome Frontiers Institute, Defense Advanced Research Projects Agency, Foundation for Polish Science and Wellcome Trust Centre.


Story Source:

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


Journal Reference:

  1. Grzegorz Kudla, Andrew W. Murray, David Tollervey, and Joshua B. Plotkin. Coding-Sequence Determinants of Gene Expression in Escherichia coli. Science, 2009; 324 (5924): 255 DOI: 10.1126/science.1170160

Cite This Page:

University of Pennsylvania. "Biologists Discover How 'Silent' Mutations Influence Protein Production." ScienceDaily. ScienceDaily, 10 April 2009. <www.sciencedaily.com/releases/2009/04/090409142258.htm>.
University of Pennsylvania. (2009, April 10). Biologists Discover How 'Silent' Mutations Influence Protein Production. ScienceDaily. Retrieved January 26, 2015 from www.sciencedaily.com/releases/2009/04/090409142258.htm
University of Pennsylvania. "Biologists Discover How 'Silent' Mutations Influence Protein Production." ScienceDaily. www.sciencedaily.com/releases/2009/04/090409142258.htm (accessed January 26, 2015).

Share This


More From ScienceDaily



More Plants & Animals News

Monday, January 26, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Water Fleas Prepare for Space Voyage

Water Fleas Prepare for Space Voyage

Reuters - Innovations Video Online (Jan. 26, 2015) Scientists are preparing a group of water fleas for a unique voyage into space. The aquatic crustaceans, known as Daphnia, can be used as a miniature model for biomedical research, and their reproductive and swimming behaviour will be tested for signs of stress while on board the International Space Station. Jim Drury went to meet the team. Video provided by Reuters
Powered by NewsLook.com
Florida Might Legalize Black Bear Hunting

Florida Might Legalize Black Bear Hunting

Newsy (Jan. 24, 2015) A string of black bear attacks has Florida officials considering lifting the ban on hunting the animals to control their population. Video provided by Newsy
Powered by NewsLook.com
Ebola Killing Large Portion Of Ape Population

Ebola Killing Large Portion Of Ape Population

Newsy (Jan. 23, 2015) Experts estimate Ebola has wiped out one-third of the world&apos;s gorillas and chimpanzees. Video provided by Newsy
Powered by NewsLook.com
Controversy Shrouds Captive Killer Whale in Miami

Controversy Shrouds Captive Killer Whale in Miami

Reuters - Light News Video Online (Jan. 23, 2015) Activists hope the National Oceanic and Atmospheric Agency (NOAA) will label killer whales endangered, allowing lawyers to sue a Miami aquarium to release an orca into the wild after 44 years. Jillian Kitchener reports. 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