RESUMO
Plasmodium knowlesi is an intracellular malaria parasite whose natural vertebrate host is Macaca fascicularis (the 'kra' monkey); however, it is now increasingly recognized as a significant cause of human malaria, particularly in southeast Asia. Plasmodium knowlesi was the first malaria parasite species in which antigenic variation was demonstrated, and it has a close phylogenetic relationship to Plasmodium vivax, the second most important species of human malaria parasite (reviewed in ref. 4). Despite their relatedness, there are important phenotypic differences between them, such as host blood cell preference, absence of a dormant liver stage or 'hypnozoite' in P. knowlesi, and length of the asexual cycle (reviewed in ref. 4). Here we present an analysis of the P. knowlesi (H strain, Pk1(A+) clone) nuclear genome sequence. This is the first monkey malaria parasite genome to be described, and it provides an opportunity for comparison with the recently completed P. vivax genome and other sequenced Plasmodium genomes. In contrast to other Plasmodium genomes, putative variant antigen families are dispersed throughout the genome and are associated with intrachromosomal telomere repeats. One of these families, the KIRs, contains sequences that collectively match over one-half of the host CD99 extracellular domain, which may represent an unusual form of molecular mimicry.
Assuntos
Genoma de Protozoário/genética , Genômica , Macaca mulatta/parasitologia , Malária/parasitologia , Plasmodium knowlesi/genética , Sequência de Aminoácidos , Animais , Antígenos CD/química , Antígenos CD/genética , Cromossomos/genética , Sequência Conservada , Genes de Protozoários/genética , Humanos , Dados de Sequência Molecular , Plasmodium knowlesi/classificação , Plasmodium knowlesi/fisiologia , Estrutura Terciária de Proteína , Proteínas de Protozoários/química , Proteínas de Protozoários/genética , Análise de Sequência de DNA , Telômero/genéticaRESUMO
During 1993-1994, scientists from developing and developed countries planned and initiated a number of parasite genome projects and several consortiums for the mapping and sequencing of these medium-sized genomes were established, often based on already ongoing scientific collaborations. Financial and other support came from WHO/TDR, Wellcome Trust and other funding agencies. Thus, the genomes of Plasmodium falciparum, Schistosoma mansoni, Trypanosoma cruzi, Leishmania major, Trypanosoma brucei, Brugia malayi and other pathogenic nematodes are now under study. From an initial phase of network formation, mapping efforts and resource building (EST, GSS, phage, cosmid, BAC and YAC library constructions), sequencing was initiated in gene discovery projects but soon also on a small chromosome, and now on a fully fledged genome scale. Proteomics, functional analysis, genetic manipulation and microarray analysis are ongoing to different degrees in the respective genome initiatives, and as the funding for the whole genome sequencing becomes secured, most of the participating laboratories, apart from larger sequencing centres, become oriented to post-genomics. Bioinformatics networks are being expanded, including in developing countries, for data mining, annotation and in-depth analysis.
Assuntos
Genoma de Protozoário , Leishmania major/genética , Trypanosoma brucei brucei/genética , Trypanosoma cruzi/genética , Animais , DNA de Protozoário/química , Leishmania major/química , Análise de Sequência de DNA , Trypanosoma brucei brucei/química , Trypanosoma cruzi/químicaRESUMO
The initiation of genome projects on helminths of medical importance promises to yield new drug targets and vaccine candidates in unprecedented numbers. In order to exploit this emerging data it is essential that the user community is aware of the scope and quality of data available, and that the genome projects provide analyses of the raw data to highlight potential genes of interest. Core bioinformatics support for the parasite genome projects has promoted these approaches. In the Brugia genome project, a combination of expressed sequence tag sequencing from multiple cDNA libraries representing the complete filarial nematode lifecycle, and comparative analysis of the sequence dataset, particularly using the complete genome sequence of the model nematode C. elegans, has proved very effective in gene discovery.
Assuntos
Filarioidea/genética , Genoma , Helmintos/genética , Animais , Brugia Malayi/genética , Caenorhabditis elegans/genética , Mapeamento Cromossômico , Biologia Computacional , Etiquetas de Sequências Expressas , Filarioidea/parasitologia , Genes de Helmintos , Helmintos/parasitologia , Schistosoma/genéticaRESUMO
Data analysis, presentation and distribution is of utmost importance to a genome project. A public domain software, ACeDB, has been chosen as the common basis for parasite genome databases, and a first release of TcruziDB, the Trypanosoma cruzi genome database, is available by ftp from ftp://iris.dbbm.fiocruz.br/pub/genomedb/Tcr uziDB as well as versions of the software for different operating systems (ftp://iris.dbbm.fiocruz.br/pub/unixsoft/). Moreover, data originated from the project are available from the WWW server at http://www.dbbm.fiocruz.br. It contains biological and parasitological data on CL Brener, its karyotype, all available T. cruzi sequences from Genbank, data on the EST-sequencing project and on available libraries, a T. cruzi codon table and a listing of activities and participating groups in the genome project, as well as meeting reports. T. cruzi discussion lists (tcruzil@iris.dbbm.fiocruz.br and tcgenics@iris.dbbm.fiocruz.br) are being maintained for communication and to promote collaboration in the genome project.