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Technique plucks rapidly evolving genes from a pathogen's genome

enetic code - that is, the translation table connecting codons to amino acids - the group was able to tell which codons were more likely to have been mutated into a codon for a different amino acid.

By counting, for example, the frequency of the six codons coding for arginine in a single gene, and comparing it to the frequency throughout the full genome, the researchers are able to determine whether the gene has likely evolved faster or slower than the genome as a whole.

"We add up over an entire gene which triplets it's using, and then we ask, 'Would we expect to see this kind of usage of triplets just by chance or not?'" Fraser said. "If not, it's unusual and gives us a clue to how the gene has been evolving."

"We need the whole genome sequence because we have to learn, for each genome, what its background distribution of triplets is," he added. "If we didn't know that, we wouldn't be able to find a gene with a significant departure from that."

The technique only works with some amino acids. The new results come from an analysis of arginine, leucine and serine, each of which is coded for by six different codons, and glycine, which coded for by four different codons.

The team, which included Jonathan Dushoff, a postdoctoral researcher at Princeton and the NIH, used its technique to analyze the 4,000 genes in the genome of the tuberculosis bacterium (Mycobacterium tuberculosis) and the 5,000 genes in the genome of the malaria parasite (Plasmodium falciparum).

The genes in these organisms that turned out to be rapidly evolving were largely those genes coding for antigens, that is, proteins that coat the surface of the pathogen and incite an immune response. By constantly changing its antigen coat, a pathogen can elude the immune system, evolving eventually into a new strain to challenge the human immune system again.

"The fact that we found most antigens were quickly evolving under our metric confirmed that ou
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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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