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.