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Technique plucks rapidly evolving genes from a pathogen's genome

do it with just a single genome sequence, instead of lining up genes from different genomes and comparing sequences."

Fraser works in the laboratory of Michael Eisen, a UC Berkeley adjunct assistant professor of molecular and cell biology and a member of the QB3 consortium (California Institute for Quantitative Biomedical Research).

"This technique can be used to quickly identify pathogenic genes that interact closely with the human immune system, since these genes are under tremendous pressure to evolve quickly," said coauthor Joshua B. Plotkin, a junior fellow in the Faculty of Arts and Sciences at Harvard. "Such genes are prime targets for new drugs and vaccines to counter deadly pathogens."

The technique involves a statistical analysis of an entire genome, comparing the rate of change of a specific gene to the average rate of change within the genome. An organism's genome is a sequence of DNA nucleotides - either A, G, T or C (for adenine, guanine, thymine and cytosine) - grouped into triplets, called codons. Each codon codes for a specific amino acid to be strung together to create a protein. The series thymine, cytosine and adenine - a TCA codon - always yields a serine amino acid, for example.

Because 64 DNA triplets can be made from the four available DNA nucleotides but there are only 20 different amino acids, some amino acids are coded by more than one codon. Arginine, for example, is coded by six different codons: CGA, CGC, CGG, CGT, AGA and AGG.

Based on an idea by Plotkin, the team zeroed in on the susceptibility of codons to point mutations - alteration of a single DNA nucleotide - and the fact that not all point mutations have the same effect. A random point mutation in some codons is less likely to create a codon that codes for a different amino acid. For example, the conversion of CGA to CGC would still result in an arginine, leaving the protein's amino acid sequence unchanged. Based on the structure of the g
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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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