Genetic Paupers May Reveal New Drug Targets

Some strains of bacteria and yeast contain dozens of genes identical to those found in much simpler life-forms, suggesting the genes are worth hanging on to. Surprisingly, however, most of these keepsakes appear to do nothing in particular to keep the organisms alive, researchers report in today's Nature Biotechnology. Why these genes and not others are retained by many species is a mystery, experts say.

A team of Swiss, German, and British scientists started their gene hunt in Mycoplasma genitalium, a bacterium with only 400 genes--genomically speaking, the simplest organism known. By running a computer program to compare the bacterium's genetic makeup to 1600 genes of unknown function in the more richly endowed Escherichia coli, they found the two species had 30 genes in common. To determine which of these 30 were essential to survival, the researchers developed "knock-out" versions of E. coli, each time deleting one gene and studying whether the bacteria were able to reproduce and grow. In only six cases did E. coli suffer after losing a gene. When the process was repeated in other bacterial pathogens, the researchers found that the same 30 genes were present but that few were essential to life.

The six indispensable genes in E. coli had never been studied closely before, says team member Hannes Loferer, head of microbiology at Munich's Genome Pharmaceuticals Corp. Such genes could be promising targets for drugs, he says. That's because further tests showed that yeast, the cells of which more closely resemble human cells, could thrive when deprived of four "essential" E. coli genes. Drug companies may be able to design antibiotics that can target vulnerable genes in bacteria without harming people, says Loferer.

Experts caution that this study is only a step toward proving that such genes play no role in survival in bacteria, yeast, or even people. A petri dish, for example, cannot completely mimic competition among organisms or other pressures faced in nature, notes Eugene Koonin, a computational biologist at the National Institutes of Health. Consequently, some single genes that may not appear to influence an individual's survival might interact with other genes to ensure that an organism flourishes. Still, Koonin says, the findings are "a first step in a direction that is necessary."

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