The filarial genome project: analysis of the nuclear, mitochondrial and endosymbiont genomes of Brugia malayi

The Filarial Genome Project (FGP) was initiated in 1994 under the auspices of the World Health Organisation. Brugia malayi was chosen as the model org anism due to the availability of all life cycle stages for the construction of cDNA libraries. To date, over 20000 cDNA clones have been partially seq uenced and submitted to the EST database (dbEST). These ESTs define approxi mately 7000 new Brugia genes. Analysis of the EST dataset provides useful i nformation on the expression pattern of the most abundantly expressed Brugi a genes, Some highly expressed genes have been identified that are expresse d in all stages of the parasites life cycle, while other highly expressed g enes appear to be stage-specific. To elucidate the structure of the Brugia genome and to provide a basis for comparison to the Caenorhabditis elegans genome, the FGP is also constructing a physical map of the Brugia chromosom es and is sequencing genomic BAC clones. In addition to the nuclear genome, B. malayi possesses two other genomes, the mitochondrial genome and the ge nome of a bacterial endosymbiont, Eighty percent of the mitochondrial genom e of B. malayi has been sequenced and is being compared to mitochondrial se quences of other nematodes. The bacterial endosymbiont genome found in B. m alayi is closely related to the Wolbachia group of rickettsia-like bacteria that infects many insect species. A set of overlapping BAC clones is being assembled to cover the entire bacterial genome. Currently, half of the bac terial genome has been assembled into four contigs. A consortium has been e stablished to sequence the entire genome of the Brugia endosymbiont, The se quence and mapping data provided by the FGP is being utilised by the nemato de research community to develop a better understanding of the biology of f ilarial parasites and to identify new vaccine candidates and drug targets t o aid the elimination of human filariasis. (C) 2000 Australian Society for Parasitology Inc. Published by Elsevier Science Ltd. All rights reserved.