Analysis of the compositional biases in Plasmodium falciparum genome and proteome using Arabidopsis thaliana as a reference.

Abstract Comparative genomic analysis of the malaria causative agent, Plasmodium falciparum , with other eukaryotes for which the complete genome is available, revealed that the genome from P. falciparum was more similar to the genome of a plant, Arabidopsis thaliana , than to other non-apicomplexan taxa. Plant-like sequences are thought to result from horizontal gene transfers after a secondary endosymbiosis involving an algal ancestor. The use of the A. thaliana genome and proteome as a reference gives an opportunity to refine our understanding of the extreme compositional bias in the P. falciparum genome that leads to a proteome-wide amino acid bias. A set of pairs of non-redundant protein homologues was selected owing to rigorous genome-wide sequence comparison methods. The introduction of A. thaliana as a reference was a mean to weight the magnitude of the protein evolutionary divergence in P. falciparum . The correlation of the amino acid proportions with evolutionary time supports the hypothesis that amino acids encoded by GC-rich codons are directionally substituted into amino acids encoded by AT-rich codons in the P. falciparum proteome. The long-term deviation of codons in malarial sequences appears as a possible consequence of a genome-wide tri-nucleotidic signature imprinting. Additionally, this study suggests possible working guidelines to improve the accuracy of P. falciparum sequence comparisons, for homology searches and phylogenetic studies.