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'Male-targeting' bacterium's genome is deciphered

Versatile Wolbachia has more mobile DNA than any other intracellular bacterium; Study may help in developing new treatments for dengue fever and other diseases

The Institute for Genomic Research

Rockville, MD - Living inside the gonad cells of more than a million species of insects, spiders, crustaceans and worms, most members of the Wolbachia family of intracellular bacteria manipulate the reproduction of their host to help ensure their own survival.

The losers in that manipulation are always the males of the host organism. Depending on the specific pair of Wolbachia and host species involved, the host males are either killed, converted into females, or prevented from successfully fertilizing the eggs of uninfected females.

Scientists have now shed light on the biology and evolution of these amazing bacteria by deciphering and analyzing the genome of a model Wolbachia strain, Wolbachia pipientis wMel, which infects the fruit fly Drosophila melanogaster, itself a model for studies of animal biology.

The new study, which appears in the March 2004 issue of PloS Biology, presents the first complete genome of a Wolbachia species. The project was supported by a grant from the National Institute of Allergy and Infectious Diseases (NIAID), which is part of the U.S. National Institutes of Health.

The investigators, led by Jonathan Eisen of The Institute for Genomic Research (TIGR), found that composition of the genome was very different from that of other intracellular bacteria. The wMel genome has accumulated more repetitive and so-called "junk" DNA (DNA for which a function cannot be identified) than any other intracellular bacteria.

Calling the Wolbachia genome "a genetic dumping ground," Eisen - an evolutionary biologist - compared it to the human Y chromosome and the knot-like centromeres in the middle of eukaryotic chromosomes. "This strain of Wolbachia has evolved in a different way than other intracellular bacteria - it appears that natural selection has been inefficient in this species, most likely because it repeatedly experiences very small population sizes," he says. "These population bottlenecks prevent natural selection from working well, more like the tossing of a coin than the survival of the fittest."

The sequencing project was done in collaboration with Scott O'Neill, an Australian biologist from the University of Queensland. He says that scientific interest in Wolbachia has intensified in recent years because the microbes infect so many arthropods and also because they influence many fundamental biological processes in their hosts.

"Wolbachia represent an excellent model for understanding fundamental interactions that occur between organisms," says O'Neill. In addition to the "intriguing evolutionary implications" of Wolbachia infections, he says research into such infections "has a lot of potential to reduce the impact of insect-transmitted diseases."

Biologists are interested in Wolbachia for many reasons, most notably the microbe's tendency to cause negative effects only to males of their host species. Such adverse impacts include:

- Parthenogenesis (infected females reproducing in the absence of mating to produce infected female offspring)
- Feminization (infected males being converted into females)
- Male-killing (infected male embryos being selectively killed), and
- Cytoplasmic incompatibility (the limiting of reproduction of uninfected females that mate with infected males).

The male-targeted effects are thought to have arisen because Wolbachia are transmitted specifically from females to their offspring and thus can increase their transmission by eliminating the non-transmitting males.

Scientists say the Wolbachia genome will be useful for researchers seeking to develop new approaches to help treat victims of lymphatic filariasis, elephantiasis, and other human diseases caused by small worms (such as Brugia malayi) that cannot survive/reproduce without Wolbachia inside their cells.

By focusing on antibiotics that kill the Wolbachia inside the worms' reproductive cells, it is possible to also kill the worms that cause those diseases. For example the genome analysis identified many genes that likely play roles in interacting with the insect host. The same genes may be involved in interacting with the worm hosts for other Wolbachia.

The genomic data are also a boon to scientists who are studying other human pathogens. For example, comparing and contrasting the genomes of Wolbachia - which do not directly cause human disease - with the closely related Rickettsia bacteria, many of which are human pathogens, may help researchers understand what genes help make Rickettsia pathogenic.

Another possible future use of the Wolbachia genome data is related to the bacterium's ability to induce "cytoplasmic incompatibility" between the sperms and eggs of some invertebrate host animals. That strategy uses Wolbachia-infected males to prevent uninfected females from producing viable offspring.

It has been proposed that cytoplasmic incompatibility might be used as a mechanism to introduce genes into certain insects that would prevent them from transmitting diseases such as dengue fever to humans. Scientists say the Wolbachia genome data will greatly accelerate progress in both understanding how Wolbachia causes cytoplasmic incompatibility and how it might best be used to develop new disease-control strategies for diseases such as dengue.

"Wolbachia studies are so informative because they are organisms that live on the edge. For example, they are beneficial to some species and detrimental to others and thus help us understand what makes one species a pathogen and another a mutualist," says Eisen.

"Since they generally only kill or negatively affect males, Wolbachia also help us learn about the mechanisms of sexual development in the host species."


The Institute for Genomic Research (TIGR) is a not-for-profit research institute based in Rockville, Maryland. TIGR, which sequenced the first complete genome of a free-living organism in 1995, has been at the forefront of the genomic revolution since the institute was founded in 1992. TIGR conducts research involving the structural, functional, and comparative analysis of genomes and gene products in viruses, bacteria, archaea, and eukaryotes.

TIGR Media Contact:
Robert Koenig, Publications and Public Affairs Manager

TIGR Scientific Contact:
Jonathan Eisen, Ph.D.

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