title: Frequent GU wobble pairings reduce translation efficiency in Plasmodium falciparum.
abstract: Plasmodium falciparum genome has 81% A+T content. This nucleotide bias leads to extreme codon usage bias and culminates in frequent insertion of asparagine homorepeats in the proteome. Using recodonized GFP sequences, we show that codons decoded via G:U wobble pairing are suboptimal codons that are negatively associated to protein translation efficiency. Despite this, one third of all codons in the genome are GU wobble codons, suggesting that codon usage in P. falciparum has not been driven to maximize translation efficiency, but may have evolved as translational regulatory mechanism. Particularly, asparagine homorepeats are generally encoded by locally clustered GU wobble AAT codons, we demonstrated that this GU wobble-rich codon context is the determining factor that causes reduction of protein level. Moreover, insertion of clustered AAT codons also causes destabilization of the transcripts. Interestingly, more frequent asparagine homorepeats insertion is seen in single-exon genes, suggesting transcripts of these genes may have been programmed for rapid mRNA decay to compensate for the inefficiency of mRNA surveillance regulation on intronless genes. To our knowledge, this is the first study that addresses P. falciparum codon usage in vitro and provides new insights on translational regulation and genome evolution of this parasite.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Box 280, Nobels väg 16, 171 65, Stockholm, Sweden. sherwin.chan@ki.se.
authors.forename: Sherwin
authors.initials: S
authors.lastname: Chan
authors.affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Box 280, Nobels väg 16, 171 65, Stockholm, Sweden.|Department of Microbiology and Immunology, National University of Singapore, Singapore, Singapore.
authors.forename: Jun-Hong
authors.initials: JH
authors.lastname: Ch'ng
authors.affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Box 280, Nobels väg 16, 171 65, Stockholm, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Wahlgren
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jessada
authors.initials: J
authors.lastname: Thutkawkorapin
mesh_terms: D000926:Anticodon; D001216:Asparagine / Q000235:genetics; D001482:Base Composition; D020029:Base Pairing; D003062:Codon; D019143:Evolution, Molecular; D005091:Exons; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D010963:Plasmodium falciparum / Q000235:genetics*; D014176:Protein Biosynthesis; D012091:Repetitive Sequences, Nucleic Acid; D012641:Selection, Genetic
chemical_list: D000926:Anticodon; D003062:Codon; D001216:Asparagine