Disease evolution plagues scientists.

Disease evolution plagues scientists

In the 14th century, the black plague stormed through Europe, killing at least one-quarter of its inhabitants. Then, as mysteriously as it had come, it disappeared. Now molecular biologists have found a clue that may help explain why diseases like the plague rise and fall -- and rise again.

The researchers base their conclusions on studies of two strains of bacteria, Yersinia pestis, which causes plague, and Yersinia pseudotuberculosis, which confers resistance to plague but causes only mild symptoms. Hans Wolf-Watz of the University of Umea, Sweden, with Roland Rosqvist and Mikael Skurnik of the Swedish Defense Research Establishment, first examined two genes believed to help Y. pseudotuberculosis invade cells. The genes code for invasin and Yop1, proteins found at the surface of Y. pseudotuberculosis. Y. pestis contains altered forms of the genes that do not produce proteins. The scientists mutated the Y. pseudotuberculosis genes for invasin, for Yop 1 or for both proteins and administered bacteria containing the altered genes to mice. They then measured the bacteria's virulence by counting the number of mice that died.

The results show that a mutation in one or the other of the two genes barely changes the bacteria's virulence, but mutations in both genes makes the bacteria remarkably more deadly. Apparently, the presence of invasin and Yop1 results in a mild, controlled infection but their absence allows bacteria to ravage cells and cause disease, the researchers say.

Next, the scientists closely examined the Yop1 genes of Y. pestis and Y. pseudotuberculosis. They found only one small genetic difference between the two strains. This difference and one in the invasin gene account for Y. pestis' virulence, they conclude.

Finally, in a sort of reverse of the first experiment, they transplanted the Yop1 gene from Y. pseudotuberculosis into Y. pestis. Confirming expectations, Y. pestis became notably less virulent.

In the Aug. 11 NATURE, the researchers propose that plague epidemics may have come and gone when nearly harmless trains like Y. pseudotuberculosis, with a flick of two genes, became Y. pestis and then, with another switch, mutated back to a nonvirulent form. But an evolutionary hypothesis cannot be based on genetics alone, says evolutionary biologist Richard Lenski of the University of California, Irvine. In an editorial accompanying the report, Lenski says other variables, such as the size of the host population, can determine the course of a disease. In a large population, many mutant forms of bacteria can exist, he explains, but when the host population is small, only the less virulent strains survive.

Lenski also mentions that similar environmental variables may be affecting the course of the AIDS-causing human immunodeficiency virus (HIV). But this possibility is highly speculative, he hastens to add. "I deliberately left the section on HIV vague," he says.