New insights into the factors affecting synonymous codon usage in human infecting Plasmodium species.

Codon usage bias is due to the non-random usage of synonymous codons for coding amino acids. The synonymous sites are under weak selection, and codon usage bias is maintained by the equilibrium in mutational bias, genetic drift and selection pressure. The differential codon usage choices are also relevant to human infecting Plasmodium species. Recently, P. knowlesi switches its natural host, long-tailed macaques, and starts infecting humans. This review focuses on the comparative analysis of codon usage choices among human infecting P. falciparum and P. vivax along with P. knowlesi species taking their coding sequence data. The variation in GC content, amino acid frequencies, effective number of codons and other factors plays a crucial role in determining synonymous codon choices. Within species codon choices are more similar for P. vivax and P. knowlesi in comparison with P. falciparum species. This study suggests that synonymous codon choice modulates the gene expression level, mRNA stability, ribosome speed, protein folding, translation efficiency and its accuracy in Plasmodium species, and provides a valuable information regarding the codon usage pattern to facilitate gene cloning as well as expression and transfection studies for malaria causing species.