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Codon Usage

Codon Usage. Discovering the codon bias. In the year 1980. Four researchers from Lyon analyzed ALL published mRNA sequences of more than about 50 codons. All together they analyzed 90 sequences….

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Codon Usage

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  1. Codon Usage

  2. Discovering the codon bias

  3. In the year 1980 Four researchers from Lyon analyzed ALL published mRNA sequences of more than about 50 codons. All together they analyzed 90 sequences…

  4. In the paper they first list all the gene studied and they compute codon frequencies for various groups: Single strand RNA viruses Single strand DNA viruses Double strand DNA viruses Double strand (DS) bacteria DS mitochondria DS yeast DS animals IgG’s.

  5. They project each sequence on 2D, so that sequences with similar codon composition appear near each other. Correspondence analysis

  6. Mostly viruses Mostly animals & bacteria

  7. Papova virus genes cluster together

  8. Ig genes cluster together

  9. Mammals genes that are not Ig cluster together

  10. The genome hypothesis All genes in a genome tend to have the same coding strategy. That is, they employ the codon catalog similarly and show similar choices between synonymous codons. Different taxa have different coding strategies. Richard Grantham

  11. An example: 21 of the 23 leucine residues in the E. coli outer membrane protein II (ompA) are encoded by the codon CUG, although 5 other codons for leucine are available.

  12. Measures of codon-usage bias

  13. The relative synonymous codon usage (RSCU) was first suggested by Sharp et al. (1986).

  14. RSCU is the number of times a codon appears in a gene divided by the number of expected occurrences under equal codon usage. n = number of synonymous codons (1 n  6) for the amino acid under study, Xi = number of occurrences of codon i.

  15. If the synonymous codons of an amino acid are used with equal frequencies, their RSCU values will equal 1.

  16. Gouy and Gautier (1982) and Bennetzen and Hall (1982) found positive correlation between degree of codon bias and level of gene expression.

  17. One can locate “optimal” codons which are expected to be translated more efficiently than others.

  18. Motivation: We now want to define the “codon bias” of a specific gene, relative to the optimal codons…

  19. The codon adaptation index (CAI) measures the degree with which genes use preferred codons. We first compile a table of RSCU values for highly expressed genes. From this table, it is possible to identify the codons that are most frequently used for each amino acid. The relative adaptiveness of a codon (wi) is computed as where RSCUmax = the RSCU value for the most frequently used codon for an amino acid.

  20. The CAI value for a gene is calculated as the geometric mean of wi values for all the codons used in that gene. where L = number of codons.

  21. Universal and species-specific patterns of codon usage

  22. Universal patterns: Codons that contain the CG dinucleotide are universally avoided (low-usage codons). This phenomenon is particularly notable as far as the arginine codons CGA and CGG are concerned.

  23. Codon Usage is related to Translation Efficiency Toshimishi Ikemura

  24. Rules determining choice of optimal codons in unicellular organisms __________________________________ 1. tRNA availability. 2. Preference for A over G when thiolated uridine or 5- carboxymethyl are at the anticodon wobble position. 3. Preference for T and C over A when inosine is at the anticodon wobble position. 4. Codons of the AAN, ATN, TAN, and TTN type prefer C in the third codon position. __________________________________

  25. Codon usage and population size If codon usage is affected by selection, the strength of such selection ought to be very week. In fact, it may be so week that random genetic drift would dominate the evolutionary dynamics of codon substitution in species with a small effective population size, whereas selection would be the dominant force in species with large effective populations sizes. Drosophilasimulans, which has a larger effective population size than D. melanogaster, also has a stronger codon bias.

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