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The effect of expression levels on codon usage in Plasmodium falciparum

  • L. PEIXOTO (a1) (a2), V. FERNÁNDEZ (a3) and H. MUSTO (a1)

The usage of alternative synonymous codons in the completely sequenced, extremely A+T-rich parasite Plasmodium falciparum was studied. Confirming previous studies obtained with less than 3% of the total genes recently described, we found that A- and U-ending triplets predominate but translational selection increases the frequency of a subset of codons in highly expressed genes. However, some new results come from the analysis of the complete sequence. First, there is more variation in GC3 than previously described; second, the effect of natural selection acting at the level of translation has been analysed with real expression data at 4 different stages and third, we found that highly expressed proteins increment the frequency of energetically less expensive amino acids. The implications of these results are discussed.

Corresponding author
Laboratorio de Organización y Evolución del Genoma, Facultad de Ciencias, Iguá 4225, Montevideo 11400, Uruguay. Tel: +598 2 5252095. Fax: +598 2 5258617. E-mail:
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AKASHI, H. & EYRE-WALKER, A. (1998). Translational selection and molecular evolution. Current Opinion in Genetics and Development 8, 688693.
AKASHI, H. & GOJOBORI, T. (2002). Metabolic efficiency and amino acid composition in the proteomes of Escherichia coli and Bacillus subtilis. Proceedings of the National Academy of Sciences, USA 99, 36953700.
AKASHI, H. (2001). Gene expression and molecular evolution. Current Opinion in Genetics and Development 11, 660666.
ALVAREZ, F., ROBELLO, C. & VIGNALI, M. (1994). Evolution of codon usage and base contents in kinetoplastid protozoans. Molecular Biology and Evolution 11, 790802.
ANDERSSON, S. G. & KURLAND, C. G. (1990). Codon preferences in free-living microorganisms. Microbiological Reviews 54, 198210.
BAHL, A., BRUNK, B., CRABTREE, J., FRAUNHOLZ, M. J., GAJRIA, B., GRANT, G. R., GINSBURG, H., GUPTA, D., KISSINGER, J. C., LABO, P., LI, L., MAILMAN, M. D., MILGRAM, A. J., PEARSON, D. S., ROOS, D. S., SCHUG, J., STOECKERT, C. J. jr. & WHETZEL, P. (2003). PlasmoDB: the Plasmodium genome resource. A database integrating experimental and computational data. Nucleic Acids Research 31, 212215.
BULMER, M. (1991). The selection-mutation-drift theory of synonymous codon usage. Genetics 129, 897907.
CARLINI, D. B. & STEPHAN, W. (2003). In vivo introduction of unpreferred synonymous codons into the Drosophila Adh gene results in reduced levels of ADH protein. Genetics 163, 239243.
COGHLAN, A. & WOLFE, K. H. (2000). Relationship of codon bias to mRNA concentration and protein length in Saccharomyces cerevisiae. Yeast 16, 11311145.
CORTAZZO, P., CERVENANSKY, C., MARIN, M., REISS, C., EHRLICH, R. & DEANA, A. (2002). Silent mutations affect in vivo protein folding in Escherichia coli. Biochemical and Biophysical Research Communications 293, 537541.
DEANA, A., EHRLICH, R. & REISS, C. (1998). Silent mutations in the Escherichia coli ompA leader peptide region strongly affect transcription and translation in vivo. Nucleic Acids Research 26, 47784782.
DUAN, J., WAINWRIGHT, M. S., COMERON, J. M., SAITOU, N., SANDERS, A. R., GELERNTER, J. & GEJMAN, P. V. (2003). Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor. Human Molecular Genetics 12, 205216.
DURET, L. & MOUCHIROUD, D. (1999). Expression pattern and, surprisingly, gene length shape codon usage in Caenorhabditis, Drosophila, and Arabidopsis. Proceedings of the National Academy of Sciences, USA 96, 44824487.
ERMOLAEVA, M. D. (2001). Synonymous codon usage in bacteria. Current Issues in Molecular Biology 3, 9197.
FERNÁNDEZ, V., ZAVALA, A. & MUSTO, H. (2001). Evidence for translational selection in codon usage in Echinococcus spp. Parasitology 123, 203209.
FLORENS, L., WASHBURN, M. P., RAINE, J. D., ANTHONY, R. M., GRAINGER, M., HAYNES, J. D., MOCH, J. K., MUSTER, N., SACCI, J. B., TABB, D. L., WITNEY, A. A., WOLTERS, D., WU, Y., GARDNER, M. J., HOLDER, A. A., SINDEN, R. E., YATES, J. R. & CARUCCI, D. J. (2002). A proteomic view of the Plasmodium falciparum life cycle. Nature, London 419, 520526.
GARDNER, M. J., HALL, N., FUNG, E., WHITE, O., BERRIMAN, M., HYMAN, R. W., CARLTON, J. M., PAIN, A., NELSON, K. E., BOWMAN, S., PAULSEN, I. T., JAMES, K., EISEN, J. A., RUTHERFORD, K., SALZBERG, S. L., CRAIG, A., KYES, S., CHAN, M. S., NENE, V., SHALLOM, S. J., SUH, B., PETERSON, J., ANGIUOLI, S., PERTEA, M., ALLEN, J., SELENGUT, J., HAFT, D., MATHER, M. W., VAIDYA, A. B., MARTIN, D. M., FAIRLAMB, A. H., FRAUNHOLZ, M. J., ROOS, D. S., RALPH, S. A., McFADDEN, G. I., CUMMINGS, L. M., SUBRAMANIAN, G. M., MUNGALL, C., VENTER, J. C., CARUCCI, D. J., HOFFMAN, S. L., NEWBOLD, C., DAVIS, R. W., FRASER, C. M. & BARRELL, B. (2002). Genome sequence of the human malaria parasite Plasmodium falciparum. Nature, London 419, 498511.
GOMAN, M., LANGSLEY, G., HYDE, J. E., YANKOVSKY, N. K., ZOLG, J. W. & SCAIFE, J. G. (1982). The establishment of genomic DNA libraries for the human malaria parasite Plasmodium falciparum and identification of individual clones by hybridisation. Molecular and Biochemical Parasitology 5, 391400.
GRANTHAM, R., GAUTIER, C., GOUY, M., JACOBZONE, M. & MERCIER, R. (1981). Codon catalog usage is a genome strategy modulated for gene expressivity. Nucleic Acids Research 9, r43r74.
GREENACRE, M. (1984). Theory and Application of Correspondence Analysis. London, Academic Press.
HYDE, J. E. & SIMS, P. F. (1987). Anomalous dinucleotide frequencies in both coding and non-coding regions from the genome of the human malaria parasite Plasmodium falciparum. Gene 61, 177187.
KANAYA, S., YAMADA, Y., KUDO, Y. & IKEMURA, T. (1999). Studies of codon usage and tRNA genes of 18 unicellular organisms and quantification of Bacillus subtilis tRNAs: gene expression level and species-specific diversity of codon usage based on multivariate analysis. Gene 238, 143155.
McCUTCHAN, T. F., DAME, J. B., MILLER, L. H. & BARNWELL, J. (1984). Evolutionary relatedness of Plasmodium species as determined by the structure of DNA. Science 225, 808811.
MUSTO, H., CACCIÒ, S., RODRIGUEZ-MASEDA, H. & BERNARDI, G. (1997). Compositional constraints in the extremely GC-poor genome of Plasmodium falciparum. Memorias do Instituto Oswaldo Cruz 92, 835841.
MUSTO, H., ROMERO, H., ZAVALA, A., JABBARI, K. & BERNARDI, G. (1999). Synonymous codon choices in the extremely GC-poor genome of Plasmodium falciparum: compositional constraints and translational selection. Journal of Molecular Evolution 49, 2735.
MUSTO, H., RODRIGUEZ-MASEDA, H. & BERNARDI, G. (1995). Compositional properties of nuclear genes from Plasmodium falciparum. Gene 152, 127132.
MUSTO, H., ROMERO, H. & ZAVALA, A. (2003). Translational selection is operative for synonymous codon usage in Clostridium perfringens and Clostridium acetobutylicum. Microbiology 149, 855863.
PERRIÈRE, G. & THIOULOUSE, J. (2001). Use and misuse of correspondence analysis in codon usage studies. Nucleic Acids Research 30, 45484555.
POLLACK, Y., KATZEN, A. L., SPIRA, D. T. & GOLENSER, J. (1982). The genome of Plasmodium falciparum. I: DNA base composition. Nucleic Acids Research 10, 539546.
ROMERO, H., ZAVALA, A. & MUSTO, H. (2000). Compositional pressure and translational selection determine codon usage in the extremely GC-poor unicellular eukaryote Entamoeba histolytica. Gene 242, 307311.
SAUL, A. & BATTISTUTTA, D. (1988). Codon usage in Plasmodium falciparum. Molecular and Biochemical Parasitology 27, 3542.
SHARP, P. M. & DEVINE, K. M. (1989). Codon usage and gene expression level in Dictyostelium discoideum: highly expressed genes do ‘prefer’ optimal codons. Nucleic Acids Research 17, 50295039.
SHARP, P. M. & LI, W. H. (1986). An evolutionary perspective on synonymous codon usage in unicellular organisms. Journal of Molecular Evolution 24, 2838.
SHARP, P. M. & MATASSI, G. (1994). Codon usage and genome evolution. Current Opinion in Genetics and Development 4, 851860.
SHARP, P. M., TUOHY, T. M. & MOSURSKI, K. R. (1986). Codon usage in yeast: cluster analysis clearly differentiates highly and lowly expressed genes. Nucleic Acids Research 14, 51255143.
SHARP, P. M., AVEROF, M., LLOYD, A. T., MATASSI, G. & PEDEN, J. F. (1995). DNA sequence evolution: the sounds of silence. Philosophical Transactions of the Royal Society of London, B 349, 241247.
SHIELDS, D. C. & SHARP, P. M. (1987). Synonymous codon usage in Bacillus subtilis reflects both translational selection and mutational biases. Nucleic Acids Research 15, 80238040.
SLIMKO, E. M. & LESTER, H. A. (2003). Codon optimization of Caenorhabditis elegans GluCl ion channel genes for mammalian cells dramatically improves expression levels. Journal of Neuroscience Methods 124, 7581.
WEBER, J. L. (1987). Analysis of sequences from the extremely A+T-rich genome of Plasmodium falciparum. Gene 52, 103109.
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