Double agent

日期:2017-04-21 07:59:18 作者:娄情倦 阅读:

By Jonathan Knight JUMPING DNA that may have helped the mammalian immune system evolve also appears to have brought with it a curse, according to researchers in the US. They have found evidence that genes which allow antibodies to mutate and attack new pathogens could also cause mutations that lead to leukaemia. Harmful microorganisms and viruses often mutate far faster than the animals they infect. The vertebrate immune system can keep up with them only because antibody genes continually change as well. Antibody genes in blood cells called B-lymphocytes mutate before becoming active when special editing proteins remove sections of the DNA. The break points are seldom the same in any two cells, so B cells make a huge variety of antibodies. David Schatz, a molecular biologist at Yale University, discovered the proteins responsible for rearranging antibody genes around a decade ago. Now his group, along with a team headed by Martin Gellet at the National Institutes of Health (NIH) near Washington DC, have independently suggested that the genes for these proteins, called RAG 1 and RAG 2, evolved from a transposon, a mobile unit of DNA that can hop into and out of chromosomes. The researchers say that the transposon probably crossed from some other organism to the genome of an ancestral mammal hundreds of millions of years ago. The teams made the discovery after adding purified RAG 1 and 2 proteins to rings of DNA in a tube. Because the DNA included two copies of the sequence of bases that the RAG proteins bind to, a chunk of DNA containing those binding sites and the sequences between them was cut out. But rather than remaining separate, the portion of DNA that had been removed was reinserted at a new position in the ring. Schatz says this suggests that the RAG genes originally came from a transposon. “Evolutionary events like this are very hard to prove,” he says, but he believes that this is good circumstantial evidence. The NIH researchers propose in the current issue of the journal Cell (vol 94, p 463) that the ability of the RAG proteins to chop out a chunk of DNA and insert it elsewhere in a chromosome could account for certain types of blood cancer. For years, researchers have found that in some leukaemia patients, part of an antibody gene has become linked to a cancer gene on a different chromosome. It’s possible that the antibody gene activates the cancer-promoting gene. According to Meni Melek, one of the members of the NIH team, no one has ever been able to explain this unnatural pairing of two gene segments. “Now we are able to mimic this process in a test tube,” she says. Schatz thinks that cells can normally prevent excised DNA being randomly reinserted. But it could be that this mechanism can go wrong, leading to cancer. “I think it’s a very interesting idea,” says Schatz,