Proteome Composition in Plasmodium falciparum: Higher Usage of GC-Rich Nonsynonymous Codons in Highly Expressed Genes

Abstract

The parasite Plasmodium falciparum, responsible for the most deadly form of human malaria, is one of the extremely AT-rich genomes sequenced so far and known to possess many atypical characteristics. Using multivariate statistical approaches, the present study analyzes the amino acid usage pattern in 5038 annotated protein-coding sequences in P. falciparum clone 3D7. The amino acid composition of individual proteins, though dominated by the directional mutational pressure, exhibits wide variation across the proteome. The Asn content, expression level, mean molecular weight, hydropathy, and aromaticity are found to be the major sources of variation in amino acid usage. At all stages of development, frequencies of residues encoded by GC-rich codons such as Gly, Ala, Arg, and Pro increase significantly in the products of the highly expressed genes. Investigation of nucleotide substitution patterns in P. falciparum and other Plasmodium species reveals that the nonsynonymous sites of highly expressed genes are more conserved than those of the lowly expressed ones, though for synonymous sites, the reverse is true. The highly expressed genes are, therefore, expected to be closer to their putative ancestral state in amino acid composition, and a plausible reason for their sequences being GC-rich at nonsynonymous codon positions could be that their ancestral state was less AT-biased. Negative correlation of the expression level of proteins with respective molecular weights supports the notion that P. falciparum, in spite of its intracellular parasitic lifestyle, follows the principle of cost minimization.

Correlation of mRNA Expression and Protein Abundance Affected by Multiple Sequence Features Related to Translational Efficiency in Desulfovibrio vulgaris: A Quantitative Analysis

“…Amino acid usage: It was observed that the usage of some amino acids was correlated with gene expression (Akashi 2003;Chanda et al 2005;Schaber et al 2005). To determine whether it is the same case for amino acid usage in D. vulgaris, we applied a similar approach to the one used for codon usage, as described in the previous section.…”

Frequent GU wobble pairings reduce translation efficiency in Plasmodium falciparum

“…These findings are consistent with earlier studies on P . falciparum codon usage where synonymous C-ending codons in the two–box codon families were described to be the optimal codons 15–17 . Our study also bridges the codon usage bias with the unique expansion of asparagine homorepeats in P .…”

“…falciparum were mainly conducted in silico , such as the computing of genome-wide ‘Relative synonymous codon usage’ values as well as describing codon optimality using ‘effective number of codons’ values between highly and lowly expressed genes 15–17, 21 . To complement these in silico studies, we used GFP reporter assays to investigate the in vitro effect of different codon usages on translation elongation in Plasmodium falciparum .…”

Selection shapes malaria genomes and drives divergence between pathogens infecting hominids versus rodents

“…In both hominid and rodent lineages, highly expressed genes are generally more constrained than less expressed genes [16]. This observation is often attributed to the fact that proteins that are expressed in more diverse cellular environments are subjected to stronger functional constraints [14,15,17].…”