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Bacterial genes tell the tale of an outbreak's evolution
Date:11/13/2011

ms Biology. When Michel and Lieberman, who share credit as first authors on the Nature Genetics paper, crunched the numbers on their B. dolosa samples, the dN/dS ratio was 1.0. Across the genomes of their entire sample set, the changes appeared perfectly random.

"It wasn't a small effect," Lieberman said. "It was no effect." But the finding defied previous observations and common sensebacteria face pressure from antibiotics, pressure from the immune system, pressure from one another. Even in test tubes, bacteria evolve.

Maybe, Lieberman suggested, they were asking the wrong question. What if the genome-wide dN/dS ratio was a red herring, when what they really wanted to know was what was happening to specific genes? "Tami had the key insight," said Kishony. If a mutation has any effect, it's typically harmful. Randomly tune your car, and you're apt to get a broken car. In a gene pool, purifying selection weeds out those harmful changes even as positive selection spreads helpful ones. Average those positive and negative effects, and both might disappear.

Sure enough, when Lieberman and Michel analyzed the same data another wayseparating genes that had mutated in multiple patients from those that had mutated just oncemost genes registered a dN/dS of slightly less than one, evidence of widespread purifying selection. Seventeen genes scored much higher, strong evidence of positive selection. Tellingly, bacteria from different patients showed pressure on the same genes, which evolved in similar ways.

"These data told us what the pathogen experiences as its main challenges," Kishony said. Some of those challenges were expected: Genes linked to antibiotic resistance, adhesion and immune response faced pressure to adapt.

One of the most striking findings among such genes was a stop codon, seen in about 70 percent of the strains, in a previously unstudied enzyme linked to genes involved in the synthesis of lipopolysaccharide (
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Contact: David Cameron
david_cameron@hms.harvard.edu
617-432-0441
Harvard Medical School
Source:Eurekalert

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