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Comparing the genomes of different strains of the same pathogen, or of closely related species of a pathogen, can help identify genes and provide valuable information about genome organisation, evolution and why some strains are harmless and others deadly. At the Wellcome Trust Sanger Institute's Pathogen Sequencing Unit (PSU), the genome of Plasmodium falciparum is being compared to that of six other Plasmodium species.
"Plasmodium falciparum is a dreadful organism to sequence," says Dr Bart Barrell, Head of the Unit. "In places, the genome DNA is 80–90 per cent As and Ts. This makes it extremely difficult to isolate, clone and sequence the DNA, and when you have some sequence it's very difficult to assemble the sequence in the right order. It's taken a lot of effort to get the sequence together."
The comparative sequencing project has helped the team identify where the genes are in the Plasmodium falciparum genome. "It's relatively easy to find genes in a bacterial genome," says Dr Barrell. "Malaria genes have introns and exons, and it's often less clear which sequences are genes and which aren't. But the genes and exons are conserved between species, so we can use comparative genomics to line the sequences up and find the coding sequences."
The project will also be sequencing a field isolate of Plasmodium falciparum. "It's possible that the cultured parasite that is used in the laboratory has lost some of its virulence," says Dr Arnab Pain, a malariologist at the PSU. "We'll be comparing all these sequences of Plasmodium, and we should get an excellent understanding of the parasite's genome and find things that can be tested in the laboratory."
Wellcome Trust Sanger Institute: Pathogen Sequencing Unit
Page of 1; 2/9/04
[WTD023854] Parasite comparative sequencing.doc