Low-Complexity Regions in Plasmodium Proteins: In Search of a Function

Members of the genus Plasmodium are responsible for malaria, a disease endemic to vast tropical and subtropical areas, causing millions of deaths each year. Of the Plasmodiumspecies that infect humans (P. falciparum, P. vivax, P. ovaleand P. malariae), P. falciparum is the most virulent. Infection can lead to cerebral malaria and to death. Understanding the complex biology and pathogenicity of Plasmodium has been a major effort of the biological and medical community, recently leading to the international project of sequencing the entire P. falciparum genome (for review, see Wellems et al. 1999). Of the 14 chromosomes of P. falciparum, the sequencing of chromosomes 2 and 3 is now complete (Gardner et al. 1998; Bowman et al. 1999). It is expected that the complete genome will allow easier identification of genes responsible for its pathogenicity and will be helpful in the development of effective vaccines. Also, the complete genome will offer an unbiased perspective on the proteome that it encodes, and a unique opportunity to discern the general properties of its coding and noncoding regions. The genome of P. falciparum is unique in many ways. Its DNA is extremely high in A + T content (∼84% for both available chromosomes). The genome is also anomalous in its “genomic signature”, which characterizes the genome composition based on dinucleotide relative abundances (Karlin et al. 1997). In contrast to most other eukaryotic genomes in which the dinucleotide TA is underrepresented, in the Plasmodium genome its relative frequency is in the normal range. However, representation of the pair CC/GG is distinctly high. These and other characteristics render thePlasmodium genome among the most different in signature of all investigated eukaryotic organisms (Karlin and Mrázek 1997, Karlin et al. 1998). The proteome of Plasmodium is as equally anomalous …