Plague organism shed genes as it grew more lethal

Sep 15, 2004 (CIDRAP News) The bacterium that causes plague, Yersinia pestis, may have acquired its lethal traits by shedding genes found in a closely related bacterium that is less dangerous, according to a recent study.

A team of researchers from Lawrence Livermore National Laboratory in California and several other centers reached this conclusion by comparing the genome of Y pestis with that of its close relative, Yersinia pseudotuberculosis. Plague is usually fatal if left untreated, whereas Y pseudotuberculosis causes a less virulent gastrointestinal illness that can be mistaken for appendicitis.

Previous studies have shown that Y pestis evolved relatively recently from Y pseudotuberculosis and is genetically very similar. The researchers found that Y pestis contains very few new genes but lacks several hundred genes found in Y pseudotuberculosis, according to the report in the Sep 21 issue of the Proceedings of the National Academy of Sciences.

The researchers spelled out the complete DNA sequence of a Y pseudotuberculosis strain called IP32953 and compared it with the genomes of two previously sequenced strains of Y pestis. The comparison revealed only 32 genes that were new in Y pestis, aside from two plasmids (extrachromosomal rings of DNA) that are unique to the bacterium.

The analysis also showed that Y pestis lacks 317 genes found in Y pseudotuberculosis, "indicating that as many as 13% of Y. pseudotuberculosis genes no longer function in Y. pestis," the report states. This "massive gene loss," along with the addition of certain DNA sequences that block gene expression, seems to have been more important than the addition of new genes in the evolution of the plague organism, the authors state.

"These results provide a sobering example of how a highly virulent epidemic clone can suddenly emerge from a less virulent closely related progenitor," the report says.

The findings suggest that natural selection may have led to the inactivation of Y pestis genes that tended to suppress the pathogen's lethality, according to a Lawrence Livermore news release. "Evolutionary pressures may have also made the bacterium better adapted to colonize the flea, its preferred vector . . . , and thus facilitate the flea-borne spread of the disease," the release says.

The lead author of the report is P. S. G. Chain of Lawrence Livermore; the team also included investigators from six other centers in the United States and France.

Chain PSG, Carniel E, Larimer FW, et al. Insights into the evolution of Yersinia pestis through whole-genome comparison with Yersinia pseudotuberculosis. Proc Natl Acad Sci 2004;101(38):13826-31 [Full text]