Parasite Breaks Its Own DNA To Avoid Detection

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 he parasite's survival strategy hinges upon its ability to change its surface copon 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.

... 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.

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.

via Parasite Breaks Its Own DNA To Avoid Detection.