BPS 4104 Chapter Notes - Chapter 8 & 9: Codon Usage Bias, Wobble Base Pair, Genetic Code
Chapter 8: Translation Codon Usage
Effect of Mutation on Codon Usage
-transitional mutations that occur at first or second codon positions are mostly non-
synonymous
-are removed from population via purifying selection
-transitional mutations that occur at third position are mostly synonymous
-can escape purifying selection & accumulate under mutation pressure
-NNN codon families are dominated by NNA codons
-most likely due to the fact that ATP has higher concentration in cell than
other rNTPs
-higher availability of ATP causes increased transcription efficiency
-deoxyribonucleotides differ in concentration with dATP being most
abundant (in mitochondria)
-this abundance increases A-based mutation rate during replication
-overall: relative abundance of necessary precursor molecules influence codon bias
-there is more energy required to make certain amino acids
-if an amino acid requires more energy, it is less likely to be used in lower
expressed genes
tRNA Anticodon Loops
-anticodon sequences share feature of being flanked by two nucleotides on either
side to dorm a look that is held together by a stem
-anticodon is flanked by two nucleotides on either side to form a look that is held
together by a stem made of the first and last 4 nucleotides
Mutation Hypothesis
-not a selectionist hypothesis
-each tRNA anticodon has to wobble to translate two or four synonymous codons
-this suggests the wobble position may not be strongly constrained
-wobble position should depend on which strand tRNA gene is located
- strand specific mutation pressure is dominant force in shaping anticodon
evolution, causing more prevalent nucleotides present in wobble positions
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Codon & Anticodon Adaptation Hypothesis
-selectionist hypothesis
-example: two synonymous codons k and j
-codon k has many cognate tRNA to translate it
-k has few or no cognate tRNA to translate it
-in order to maximize translation efficiency in highly expressed genes, we predict
that natural selection should favour the use of codon k against codon j
-this leads to a strong association between frequently used codons and the
abundance of the tRNA
-mutation is considered to be disruptive to the evolution & maintenance of codon-
anticodon adaptation
-mutation reduces codon usage bias & disrupts codon-anticodon adaptation
-there has been no empirical evidence of mutation pressure that maintains codon
bias
-there is also no evidence of codon usage bias driving tRNA bias
-tRNA bias therefore drives codon usage bias
Wobble Versatility Hypothesis
-selectionist hypothesis
-each synonymous codon family is translated by a single tRNA species in vertebrate
mitochondria
-versatility of this single tRNA in translating two or four codons are important for
translation machinery
-ex: two fold degenerate codons ending with C or U are translated by tRNA with a
wobble G
-G can pair with both C and U
-two-fold degenerate codons ending with A or G are translated by tRNA with a
wobble U
-U can pair with both A and G
-four fold degenerate codons re translated by tRNA with a wobble U
-U is very versatile in pairing with other nucleotides
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Document Summary
Transitional mutations that occur at first or second codon positions are mostly non- synonymous. Transitional mutations that occur at third position are mostly synonymous. Can escape purifying selection & accumulate under mutation pressure. Nnn codon families are dominated by nna codons. Most likely due to the fact that atp has higher concentration in cell than other rntps. Higher availability of atp causes increased transcription efficiency. Deoxyribonucleotides differ in concentration with datp being most abundant (in mitochondria) This abundance increases a-based mutation rate during replication. Overall: relative abundance of necessary precursor molecules influence codon bias. There is more energy required to make certain amino acids. If an amino acid requires more energy, it is less likely to be used in lower expressed genes trna anticodon loops. Anticodon sequences share feature of being flanked by two nucleotides on either side to dorm a look that is held together by a stem.