Featured Research

from universities, journals, and other organizations

Random fluctuations give rise to odd genetic phenomenon

Date:
February 18, 2010
Source:
Massachusetts Institute of Technology
Summary:
Biophysicists have demonstrated that some cases of incomplete penetrance are controlled by random fluctuations in gene expression.

Despite identical genes and a shared environment, only some mutant nematode embryos develop a gut, which appears violet in this photomicrograph.
Credit: Arjun Raj and Scott Rifkin

For years, biologists have wondered how it is possible that not every person who carries a mutated gene expresses the trait or condition associated with the mutation. This common but poorly understood phenomenon, known as incomplete penetrance, exists in a wide range of organisms, including humans.

Related Articles


Many mutations in genes that are linked to diseases, including Parkinson's disease and Type 1 diabetes, are incompletely penetrant. Some of this variation may be due to environmental factors and the influence of other genes, but not all: It has been shown that genetically identical organisms living in the same environment can show variability in some incompletely penetrant traits.

Now, a team of MIT biophysicists has demonstrated that some cases of incomplete penetrance are controlled by random fluctuations in gene expression.

"It's not just nature or nurture," says Alexander van Oudenaarden, leader of the research team and a professor of physics and biology at MIT. "There is a random component to this. Molecules bounce around and find each other probabilistically. It doesn't work like clockwork."

In a study of intestinal development of C. elegans, a small worm, the team was able to pinpoint specific fluctuations that appear to determine whether the mutant trait is expressed or not.

The work, published in Nature on Feb. 18, may also be relevant to human diseases that display incomplete penetrance, such as Parkinson's disease and Type 1 diabetes, says van Oudenaarden. For example, knowing the specific points in cellular pathways that are most important in controlling a cell's response to mutation could give drug designers better targets for new therapies.

The team studied the embryonic development of the digestive tract of C. elegans. The tract starts out as a single cell and eventually becomes 20 cells in the adult worm. That process is initiated by a gene called skn-1, which activates a series of other genes. Most of those genes code for transcription factors, which bind to DNA and turn on additional genes.

The team first characterized normal progression of intestine development, using a probe the team members developed that binds to messenger RNA inside cells, allowing them to count the number of copies of a particular messenger RNA sequence. (Messenger RNA carries DNA's instructions to the cell's protein-building machinery.)

They then studied worms with a mutation in skn-1, and found that some of the worms developed normal digestive tracts while others failed to develop a digestive tract. It appears that the controlling factor is the number of copies of mRNA produced by a gene called end-1, one of the genes activated by skn-1. The number of end-1 mRNA strands varied greatly in embryos with the mutation: In those with a number above a certain threshold, development proceeded normally; if the number was below the threshold, no digestive tract developed.

It appears that evolution has produced networks of genes that smooth out the effects of those fluctuations, which are revealed only when there is a mutation in the pathway, says van Oudenaarden.

Van Oudenaarden plans to use the same technique to study mammalian colon stem cells, in hopes of figuring out whether random fluctuations in gene expression influence the mutations that can cause cancer. If he can show that random fluctuations in a particular gene appear to be subject to the same threshold effect that he saw in C. elegans embryonic development, it could give drug designers new targets.


Story Source:

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


Journal Reference:

  1. Arjun Raj, Scott Rifkin, Erik Andersen, Alexander van Oudenaarden. Variability in gene expression underlies incomplete penetrance. Nature, February 18, 2010 DOI: 10.1038/nature08781

Cite This Page:

Massachusetts Institute of Technology. "Random fluctuations give rise to odd genetic phenomenon." ScienceDaily. ScienceDaily, 18 February 2010. <www.sciencedaily.com/releases/2010/02/100217131121.htm>.
Massachusetts Institute of Technology. (2010, February 18). Random fluctuations give rise to odd genetic phenomenon. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2010/02/100217131121.htm
Massachusetts Institute of Technology. "Random fluctuations give rise to odd genetic phenomenon." ScienceDaily. www.sciencedaily.com/releases/2010/02/100217131121.htm (accessed October 25, 2014).

Share This



More Plants & Animals News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deep Sea 'mushroom' Could Be Early Branch on Tree of Life

Deep Sea 'mushroom' Could Be Early Branch on Tree of Life

Reuters - Innovations Video Online (Oct. 24, 2014) Miniature deep sea animals discovered off the Australian coast almost three decades ago are puzzling scientists, who say the organisms have proved impossible to categorise. Academics at the Natural History of Denmark have appealed to the world scientific community for help, saying that further information on Dendrogramma enigmatica and Dendrogramma discoides could answer key evolutionary questions. Jim Drury has more. Video provided by Reuters
Powered by NewsLook.com
Black Bear Cub Goes Sunday Shopping

Black Bear Cub Goes Sunday Shopping

Reuters - Light News Video Online (Oct. 23, 2014) Price check on honey? Bear cub startles Oregon drugstore shoppers. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
Dances With Wolves in China's Wild West

Dances With Wolves in China's Wild West

AFP (Oct. 23, 2014) One man is on a mission to boost the population of wolves in China's violence-wracked far west. The animal - symbol of the Uighur minority there - is under threat with a massive human resettlement program in the region. Duration: 00:41 Video provided by AFP
Powered by NewsLook.com
Breakfast Debate: To Eat Or Not To Eat?

Breakfast Debate: To Eat Or Not To Eat?

Newsy (Oct. 23, 2014) Conflicting studies published in the same week re-ignited the debate over whether we should be eating breakfast. Video provided by Newsy
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