Toxoplasma gondii genomics: shedding light on pathogenesis and chemotherapy

Abstract

The parasitic protozoan Toxoplasma gondii and its relatives (e.g. Plasmodium spp., which cause malaria) constitute a major global health problem. In recent years, the elucidation of biological processes in these parasites has accelerated with the application of genetic and genomic methodologies. Genetic analyses in T. gondii have revealed a remarkably stable 87 Mb (megabase) nuclear genome consisting of 11 chromosomes showing little variation across strains. Population studies demonstrate that the small amount of variation defines three clonal lineages where phenotypes such as virulence are associated with a single lineage. The random generation of cDNA (complementary DNA) sequences derived from different strains and developmental stages has highlighted the genetic differences underlying observed phenotypic variation. T. gondii also contains an extrachromosomal 35 kb (kilobase) circular DNA within an organelle with plastid-like properties. The limited coding capacity of the 35 kb organellar genome suggests that proteins responsible for organelle function(s) must be encoded by the nucleus. Scrutiny of T. gondii nuclear cDNA sequences has uncovered a number of proteins thought to carry out essential roles in the organelle (e.g. fatty acid biosynthesis). The synergism between these seemingly unrelated genomic studies has provided a greater understanding of parasite pathogenesis and has identified several new targets for chemotherapy.