Featured Research

from universities, journals, and other organizations

Genetic Stowaways May Contribute To Evolutionary Change: Adjacent Sequences Tag Along With Mobile DNA Elements, Study Shows

Date:
March 8, 1999
Source:
University Of Pennsylvania Medical Center
Summary:
In the century and more since Charles Darwin first advanced his theory of evolution, the proposal has come to dominate biological understanding. Current thinking has it that new traits arise spontaneously through genetic mutations, and, if they promote the survival of the individual, the genes may be selected for in subsequent generations. Over time, significant changes in a species can occur in this way -- indeed, entirely new species may eventually appear.

In the century and more since Charles Darwin first advanced his theory of evolution, the proposal has come to dominate biological understanding. Current thinking has it that new traits arise spontaneously through genetic mutations, and, if they promote the survival of the individual, the genes may be selected for in subsequent generations. Over time, significant changes in a species can occur in this way -- indeed, entirely new species may eventually appear.

Related Articles


In this age of molecular biology, highly specific new questions about the process of evolution are being framed. Scientists would like to know whether and how evolution operates at the molecular level in an organism's DNA.

Now, experiments performed at the University of Pennsylvania Medical Center have revealed a molecular mechanism that may be a significant driver of evolution in humans and other mammals. Certain retrotransposons -- bits of DNA able to copy themselves from one region of the genome to another -- are able to pick up flanking genetic sequences and then insert themselves and the tag-along DNA at new locations. A report on the new study will appear in the March 5, 1999, issue of Science. (Advance copies of the paper are available to reporters through the journal's news office at 202-326-6421.)

"These findings suggest a new mechanism for shuffling important genetic sequences -- exons, promoters, enhancers -- that may lie downstream from these active mobile DNA elements," says Haig H. Kazazian, MD, chairman of the department of genetics and senior author on the paper. "From an evolutionary perspective, here is a way to create novel genetic combinations. While many such changes might prove lethal, some could improve function in individuals, leading to a selective advantage for those individuals."

"Previously proposed explanations for how such rearrangements of DNA might occur have been rather murky," says lead author John V. Moran, PhD, now an assistant professor of human genetics and internal medicine at the University of Michigan Medical School. "This mechanism, however, provides a relatively straightforward and powerful means for generating genomic diversity."

Working with a family of retrotransposons called long interspersed nuclear elements, also known as LINE-1s or L1s, the scientists performed two groups of experiments in cultured human cells. Between 30 and 60 active L1s are estimated to exist within the human genome. Other species, such as the mouse, are thought to have as many as 3,000 such elements in their DNA.

The aim of the first experiments was to discover whether L1s retrotranspose efficiently into genes and, if so, how often. To do this, the investigators engineered an L1 to include a marker sequence that would only be activated when the mobile L1 inserted itself into a working gene, a gene subject to transcription. The results showed that a minimum of 6 percent of all retrotransposition events effectively targeted genes. Because the total fraction of the human genome estimated to be functioning genes is only about 15 percent, this finding suggests little or no bias against genes as sites for retrotransposition.

The second set of experiments was designed to ascertain whether L1s are capable of copying and moving DNA sequences adjacent to themselves during retrotransposition. Earlier results had suggested this possibility, beginning with the surprising observation that a flanking sequence had accompanied an instance of retrotransposon insertion into the gene responsible for Duchenne's muscular dystrophy. Additional examples of such stowaway DNA with the L1s were subsequently found.

"Several years ago, we found a retrotransposon insertion into a dystrophin gene that carried about 600 base pairs of flanking sequence," says Kazazian. "When we looked elsewhere in the genome for the precursor of that insertion, we found that same 600 base pairs with the precursor."

The scientists already knew that at one end of an L1 is a sequence that initiates transcription and at the other is a sequence that terminates transcription. Closer analysis, however, revealed that the L1s use a terminating sequence that is both unusual and somewhat weak, leading to so-called readthrough, meaning that transcription at times continues past what would ordinarily have been the stop point to the next downstream termination sequence.

To better understand this readthrough phenomenon, the scientists engineered an L1 with its marker sequence outside the L1, beyond the naturally occurring termination signal. And then beyond the marker itself, they placed a well-understood and highly efficient stop signal sequence, so that the gene products of any readthrough events could be easily identified because they would end with this marker. With the stronger downstream signal in place, the engineered L1s readily picked up neighboring DNA for retrotransposition.

"Overall, we found that, not only can these retrotransposons jump into genes, but readthrough events that pick up flanking DNA are not uncommon," Moran says.

In addition to Kazazian and Moran, the third author on the paper is graduate student Ralph J. DeBerardinis. While at Penn, Moran was supported by a Damon Runyon postdoctoral fellowship. Primary funding for the study was provided by the National Institutes of Health.

The University of Pennsylvania Medical Center's sponsored research and training ranks third in the United States based on grant support from the National Institutes of Health, the primary funder of biomedical research and training in the nation -- $175 million in federal fiscal year 1997. In addition, for the third consecutive year, the institution posted the highest annual growth in these areas -- 17.6 percent -- of the top ten U.S. academic medical centers.


Story Source:

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


Cite This Page:

University Of Pennsylvania Medical Center. "Genetic Stowaways May Contribute To Evolutionary Change: Adjacent Sequences Tag Along With Mobile DNA Elements, Study Shows." ScienceDaily. ScienceDaily, 8 March 1999. <www.sciencedaily.com/releases/1999/03/990308054849.htm>.
University Of Pennsylvania Medical Center. (1999, March 8). Genetic Stowaways May Contribute To Evolutionary Change: Adjacent Sequences Tag Along With Mobile DNA Elements, Study Shows. ScienceDaily. Retrieved November 26, 2014 from www.sciencedaily.com/releases/1999/03/990308054849.htm
University Of Pennsylvania Medical Center. "Genetic Stowaways May Contribute To Evolutionary Change: Adjacent Sequences Tag Along With Mobile DNA Elements, Study Shows." ScienceDaily. www.sciencedaily.com/releases/1999/03/990308054849.htm (accessed November 26, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Wednesday, November 26, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

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
Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Newsy (Nov. 25, 2014) — Need another reason to eat yogurt every day? Researchers now say it could reduce a person's risk of developing type 2 diabetes. Video provided by Newsy
Powered by NewsLook.com
Madagascar Working to Contain Plague Outbreak

Madagascar Working to Contain Plague Outbreak

AFP (Nov. 24, 2014) — Madagascar said Monday it is trying to contain an outbreak of plague -- similar to the Black Death that swept Medieval Europe -- that has killed 40 people and is spreading to the capital Antananarivo. Duration: 00:42 Video provided by AFP
Powered by NewsLook.com
Are Female Bosses More Likely To Be Depressed?

Are Female Bosses More Likely To Be Depressed?

Newsy (Nov. 24, 2014) — A new study links greater authority with increased depressive symptoms among women in the workplace. 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

 

Health & Medicine

Mind & Brain

Living & Well

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