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Archive for the ‘Parasitology’ Category

Entamoeba histolytica is one of the most widespread and clinically important parasites, causing both serious intestinal (amoebic colitis) and extraintestinal (amoebic liver abscess) diseases throughout the world. A recent World Health Organization estimate (WHO, 1998) places E. Histolytica second after Plasmodium falciparum as causing the most deaths annually (70,000) among protistan parasites. Recently a draft of the complete genome of E. histolytica was published (Loftus et al., 2005) making it one of the first protist genomes to be sequenced.

The E. histolytica genome project was initiated in 2000 with funding from the Wellcome Trust and the National Institute of Allergy and Infectious Diseases to the Wellcome Trust Sanger Institute and The Institute for Genomic Research (TIGR) in the UK and the USA, respectively. The publication describing the draft sequence concentrated on the expanded gene families, metabolism and the role of horizontal gene transfer in the evolution of E. histolytica. In this chapterwe summarise the structure and content of the E. histolytica genome in comparison to other sequenced parasitic eukaryotes, provide a description of the current assembly and annotation, place the inferred gene content in the context of what is known about the biology of the organism and discuss plans for completing the E. histolytica genome project and extending genome sequencing to other species of Entamoeba.

The fact that the genome sequence is still a draft has several important consequences. The first is that a few genes may be missing from the sequence data we have at present, although the number is likely to be small. For example, at least one gene (amoebapore B) is not present in the genome data despite it having been cloned, sequenced and the protein extensively characterised well before the start of the genome project. The second consequence is that the assembly contains a number of large duplicated regions that may be assembly artefacts, meaning that the number of gene copies is overestimated in several cases. These problems cannot as yet be resolved but should be eventually as more data becomes available.

Nevertheless, it is important to remember these issues when reading the rest of this chapter. As the number of genes in E. histolytica runs into several thousands, it is not possible to discuss all of them. However, we have generated a number of tables that identify many genes and link them to their entries in GenBank using the relevant protein identifier. Only a few tables are included in the text of this chapter, but the others are available online as supplementary material, http://pathema.tigr.org/pathema/entamoeba_resources.shtml.

The E. histolytica genome project data are being ‘curated’ at the J. Craig Venter Institute (JCVI, formerly TIGR), and it is on that site that the most current version of the assembled genomewill be found. The ‘Pathema’ databasewill hold the data and the annotation (http://pathema.tigr.org/). The gene tables are also linked to the appropriate entry in the Pathema database, and the links will be maintained as the genome structure is refined over time. Reference is made throughout the text to other species of Entamoeba where data are available.

Entamoeba dispar is the sister species to E. histolytica and infects humans without causing symptoms. Entamoeba invadens is a reptilian parasite that causes invasive disease, primarily in snakes and lizards, and is widely used as a model for E. histolytica in the study of encystation, although the two species are not very closely related (Clark et al., 2006b). Genome projects for both these species are under way at TIGR, and it is anticipated that high-quality draft sequences will be produced for both in the near future.

It is hoped that the E. Dispar sequence will prove useful in identifying genomic differences linked to disease causation while that of E. invadens will be used to study patterns of gene expression during encystation. Small-scale genome surveys have been performed for two other species: Entamoeba moshkovskii, which is primarily a free-living species although it occasionally infects humans, and Entamoeba terrapinae, a reptilian commensal species, http://www.sanger.ac.uk/Projects/Comp_Entamoeba/