Codon Usage

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Codon Usage
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Discovering the codon bias
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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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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 IgGs.
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They project each sequence on 2D, so that
sequences with similar codon composition appear
near each other.
Correspondence analysis
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Mostly animals bacteria
Mostly viruses
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Papova virus genes cluster together
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Ig genes cluster together
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Mammals genes that are not Ig cluster together
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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
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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.
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Measures of codon-usage bias
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The relative synonymous codon usage (RSCU) was
first suggested by Sharp et al. (1986).
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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.
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If the synonymous codons of an amino acid
are used with equal frequencies, their RSCU
values will equal 1.
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Gouy and Gautier (1982) and Bennetzen and Hall
(1982) found positive correlation between degree
of codon bias and level of gene expression.
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One can locate optimal codons which are
expected to be translated more efficiently than
others.
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Motivation We now want to define the codon
bias of a specific gene, relative to the optimal
codons
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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.
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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.
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Universal and species-specific patterns of codon
usage
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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.
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Codon Usage is related to Translation Efficiency
Toshimishi Ikemura
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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. __________________________________
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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. Drosophila simulans, which
has a larger effective population size than D.
melanogaster, also has a stronger codon bias.