LAS VEGAS--Genomicists call it the toughest microbe they ever took on. But now, an international group finally has presented a first view of the full genome of Plasmodium falciparum, the most important malaria parasite. A project to sequence the genome, begun 6 years ago, is almost finished and the results could be published this summer.
The P. falciparum genome, some 30-million-base-pairs on 14 chromosomes, was cracked in a joint effort by the Sanger Centre in the United Kingdom, The Institute for Genomic Research (TIGR) in Rockville, Maryland, the U.S. Naval Medical Research Center in Silver Spring, Maryland, and Stanford University. The main reason the 6-year project became a "real nightmare," says TIGR's Malcolm Gardner, is that Plasmodium's DNA is unstable when it's reproduced in bacteria--a necessary step before the actual sequencing--and is difficult to sequence. That's because 80% of the organism's genome is composed of adenine and thymine, two of the four building blocks of DNA. (The ratio is about 59% in humans.) After developing new techniques and software to overcome those problems, the teams now have the sequence almost complete. Just over 500 gaps remain, most of them in three particularly difficult chromosomes, Gardner told the Second Conference on Microbial Genomes yesterday.
Most of the Plasmodium sequence has already been put in public databases and has been "tremendously helpful" for scientists searching for new drugs and vaccines, says Stewart Shuman of the Sloan-Kettering Institute in New York City, one of many researchers who have dredged the data and come up with new drug targets. Indeed, the project "has really energized the field and brought it together," says Dyann Wirth, director of the Harvard Malaria Initiative.
The announcement marks the beginning of what should be a banner year for malaria research. The TIGR team has also sequenced the genome of Plasmodium yoelii, which causes malaria in rodents, and is working on the less-dangerous human parasite Plasmodium vivax. The Sanger Centre, meanwhile, has taken on several other Plasmodium species. Those additional genomes should help identify what exactly makes P. falciparum so deadly for humans. To top it off, another international consortium plans to publish the genomic sequence of the most important malaria mosquito, Anopheles gambiae, also this year.
TIGR's Plasmodium project
The Sanger Centre's page about protozoan genomes
PlasmoDB, a central database where the Plasmodium sequence data is stored
A Science story about drug development in malaria