Featured Research

from universities, journals, and other organizations

Parasite Breaks Its Own DNA To Avoid Detection

Date:
April 19, 2009
Source:
Rockefeller University
Summary:
The parasite that causes African sleeping sickness is like a thief donning a disguise. Every time the host's immune cells get close to destroying the parasite, it escapes detection by rearranging its DNA and changing its appearance. Now scientists reveal how the parasite initiates its getaway, by cleaving both strands of its DNA.

The parasite Trypanosoma brucei, which causes African sleeping sickness, is like a thief donning a disguise. Every time the host's immune cells get close to destroying the parasite, it escapes detection by rearranging its DNA and changing its appearance. Now two laboratories at Rockefeller University have joined forces to reveal how the parasite initiates its getaway, by cleaving both strands of its DNA.

The parasite's survival strategy hinges upon its ability to change its surface coat. The genes that encode the current coat, which is comprised entirely of molecules called variant surface glycoproteins (VSG), are located in 15 to 20 regions near the ends of chromosomes. When the host's immune system has just about killed all of the parasites, some surviving parasites rearrange their DNA and switch their coat, initiating another wave of infection. During this cat-and-mouse game, the immune system never gains the upper hand and the victim dies.

In 2007, George A.M. Cross, head of the Laboratory of Molecular Parasitology, and Oliver Dreesen, a former postdoc in the lab, published a model suggesting that the length of telomeres, which cap the ends of chromosomes, regulate the frequency with which the parasite changes its surface coat. When the telomeres become critically short, they predicted, a break occurs in or adjacent to the actively transcribed VSG gene and triggers a switch.

"Based on the observations we made in 2007, we predicted that doubled-stranded DNA breaks were behind the switch, but we were not able to prove it," says Dreesen, who is now at the Institute of Medical Biology in Singapore. But that all changed when Nina Papavasiliou, head of the Laboratory of Lymphocyte Biology, and Catharine Boothroyd, a postdoc in Nina's lab, began collaborating with Dreesen and Cross, who is Andrι and Bella Meyer Professor at Rockefeller.

"Nina and Catharine had the perfect system to address whether this model was correct or not," says Dreesen. "They had developed a greatly improved assay to measure switching frequency, which is incredibly important, but what was key was that they were able to artificially put breaks upstream of the active VSG gene and see whether or not the surface coat changed."

By working with a DNA-cleaving enzyme from yeast, the team found that a DNA break in a specific region upstream of the active VSG gene causes the parasite to increase its coat-switching frequency by 250 times. During this break-induced recombination, a VSG gene from another chromosome is duplicated and then displaces the previously active VSG gene.

"That was an exciting find," says Boothroyd, "because duplicative gene conversion is the way trypanosomes in the wild also switch their surface coats." As Boothroyd points out, it is also how antibody-producing cells called B lymphocytes chop up and rearrange their DNA in order to destroy the virtually limitless number of foreign invaders that can infect us.

In order for duplicative gene conversion to occur, the team found that the double-stranded breaks occur naturally and specifically in a region upstream of the active VSG gene. It had long been speculated that this conserved repetitive region was important for VSG switching to occur but it had never been experimentally tested. "So detecting these breaks was a critical finding," says Cross. "Something that had not been possible prior to the application of these new techniques."

When the team looked at their first set of data, it not only fit exactly into Dreesen and Cross's prediction but it also suggested a common mechanism by which parasites and humans rearrange their DNA. "It was unbelievable," Dreesen says. "One experiment after another and it just worked."


Story Source:

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


Journal Reference:

  1. Catharine E. Boothroyd, Oliver Dreesen, Tatyana Leonova, K. Ina Ly, Luisa M. Figueiredo, George A.M. Cross and F. Nina Papavasiliou. A yeast-endonuclease-generated DNA break induces antigenic switching in Trypanosoma brucei. Nature, April 15, 2009 DOI: 10.1038/nature07982

Cite This Page:

Rockefeller University. "Parasite Breaks Its Own DNA To Avoid Detection." ScienceDaily. ScienceDaily, 19 April 2009. <www.sciencedaily.com/releases/2009/04/090415141210.htm>.
Rockefeller University. (2009, April 19). Parasite Breaks Its Own DNA To Avoid Detection. ScienceDaily. Retrieved September 19, 2014 from www.sciencedaily.com/releases/2009/04/090415141210.htm
Rockefeller University. "Parasite Breaks Its Own DNA To Avoid Detection." ScienceDaily. www.sciencedaily.com/releases/2009/04/090415141210.htm (accessed September 19, 2014).

Share This



More Health & Medicine News

Friday, September 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Could Grief Affect The Immune Systems Of Senior Citizens?

Could Grief Affect The Immune Systems Of Senior Citizens?

Newsy (Sep. 19, 2014) — The study found elderly people are much more likely to become susceptible to infection than younger adults going though a similar situation. Video provided by Newsy
Powered by NewsLook.com
Jury Delivers Verdict in Salmonella Trial

Jury Delivers Verdict in Salmonella Trial

AP (Sep. 19, 2014) — A federal jury has convicted three people in connection with an outbreak of salmonella poisoning five years ago that sickened hundreds of people and was linked to a number of deaths. (Sept. 19) Video provided by AP
Powered by NewsLook.com
How The 'Angelina Jolie Effect' Increased Cancer Screenings

How The 'Angelina Jolie Effect' Increased Cancer Screenings

Newsy (Sep. 19, 2014) — Angelina's Jolie's decision to undergo a preventative mastectomy in 2013 inspired many women to seek early screenings for the disease. Video provided by Newsy
Powered by NewsLook.com
The Cost of Ebola

The Cost of Ebola

Reuters - Business Video Online (Sep. 18, 2014) — As Sierra Leone prepares for a three-day "lockdown" in its latest bid to stem the spread of Ebola, Ciara Lee looks at the financial implications of fighting the largest ever outbreak of the disease. 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:
from the past week

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