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Technique plucks rapidly evolving genes from a pathogen's genome

Berkeley - A quick new technique able to identify genes that evolve rapidly as well as those that change slowly already has pinpointed new targets for researchers developing drugs against tuberculosis and malaria, and it could do the same for other infectious diseases, according to a paper in this week's Nature.

The technique, reported in the April 29 issue of the journal, was developed by researchers from the University of California, Berkeley, Harvard and Princeton universities, and the National Institutes of Health.

Genes that change slowly or not at all in an organism, or from one organism to another, usually turn out to be critical pieces of molecular machinery and, in an infectious organism, attractive targets for researchers hoping to kill it

Alternatively, genes that change rapidly are presumed to be under selective evolutionary pressure, such as the need for a microbe to continually switch its outer coat to escape detection by the human immune system. Such genes can tell researchers how organisms outwit the immune system or develop drug resistance.

This new technique is a total departure from current methods of finding rapidly evolving genes, and has already pinpointed previously unknown genes in the tuberculosis and malaria parasites that could be potential drug targets.

"In the typical comparative method, researchers take equivalent genes from several organisms, like humans and chimps and mice, line them up and count the differences," explained coauthor Hunter B. Fraser, a graduate student in molecular and cell biology at UC Berkeley. "That gives you an idea of what kinds of changes a gene has undergone over evolution, and from the kinds of changes you see, you can infer something about the way it is evolving - whether it has been pressured to change or pressured to stay the same.

"We're coming out with a similar end result - knowing what kinds of evolutionary pressures are on different genes - but we can
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Contact: Robert Sanders
rls@pa.urel.berkeley.edu
510-643-6998
University of California - Berkeley
29-Apr-2004


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