Trends in Parasitology
Update
Research FocusTranscription and coregulation of multigene families in Plasmodium falciparum
Research Focus
Section snippets
The subtelomeric gene families of Plasmodium falciparum
Telomeres are sites of specialized expression, recombination and localization within the nucleus. Pathogens such as Candida glabrata, Pneumocystis carinii and Trypanosoma brucei exploit the properties of telomeres by having genes that are important for pathogenesis and immune evasion encoded within subtelomeric regions 1, 2, 3. The subtelomeric regions of P. falciparum are enriched with members from three major multigene families that encode variant proteins: var, which encodes P. falciparum
Is transcription of var and stevor coregulated?
P. falciparum coregulates expression of some genes that share physical proximity within the chromosomes based on their stage-specific expression [10] and/or their functional relationship [11]. Therefore, it is possible that members of the different P. falciparum multigene families that are located within the subtelomeric regions are coregulated. Transcription of a single, dominant var gene peaks early in the intra-erythrocytic life cycle of the parasite 12, 13 and is followed later [7] by
var and stevor transcription in gametocytes
P. falciparum gametocytes take up to ten days to reach maturity. It is unknown how the parasite evades the human immune system during this time and what ligands mediate the adhesion of gametocyte-containing IEs to various host receptors. STEVOR, PfEMP1 and RIFIN are all candidates that are present in gametocytes [11] but only STEVOR has been shown to be associated with the gametocyte-containing IE membrane, although it is not known whether they are exposed on the IE surface [8]. Sharp et al.
Antigenic constraints
The observation by Sharp et al. that transcripts from a restricted repertoire of stevor genes dominate in parasites in IEs indicates a var gene-like model in which restricted expression of stevor protects the majority of the stevor repertoire from exposure to the immune system. A strategy of preserving the antigenic repertoire is also consistent with the findings of Sharp et al. that var and stevor transcription is not coregulated. Coregulation that leads to linked expression of variant surface
Acknowledgements
We thank Stuart Ralph and Stephen Rogerson for their advice on this manuscript
References (28)
A simple RNA analysis method shows var and rif multigene family expression patterns in Plasmodium falciparum
Mol. Biochem. Parasitol.
(2000)Heterochromatin silencing and locus repositioning linked to regulation of virulence genes in Plasmodium falciparum
Cell
(2005)Telomeric heterochromatin propagation and histone acetylation control mutually exclusive expression of antigenic variation genes in malaria parasites
Cell
(2005)- et al.
The molecular biology of the SIR proteins
Gene
(2001) Virulence-related surface glycoproteins in the yeast pathogen Candida glabrata are encoded in subtelomeric clusters and subject to RAP1- and SIR-dependent transcriptional silencing
Genes Dev.
(2003)- et al.
MSG gene cluster encoding major cell surface glycoproteins of rat Pneumocystis carinii
DNA Res.
(1994) Antigenic variation in trypanosomes
Arch. Med. Res.
(1996)Genome sequence of the human malaria parasite Plasmodium falciparum
Nature
(2002)Small, clonally variant antigens expressed on the surface of Plasmodium falciparum-infected erythrocytes are encoded by the rif gene family and are targets of human immune responses
J. Exp. Med.
(1999)Rifins: a second family of clonally variant proteins expressed on the surface of red cells infected with Plasmodium falciparum
Proc. Natl. Acad. Sci. U. S. A.
(1999)