What is Codon Optimisation?
Codon optimisation is the process of improving the nucleotide sequence for expression in a target organism (such as E. coli or Vibrio natriegens).1 This process exploits the synonymous nature of codons - multiple different codons can code for the same amino acid.
Codon biases are observed in species1, so expressing an E. coli protein in S. cerevisiae may require the codons to be optimised to ensure efficient expression. There are online tools to optimise codons for efficient expression in a range of species.
Optimisation involves making mutations in the sequence of interest that do not alter the protein sequence, but improve translation of the mRNA.2 Since the advent of affordable DNA synthesis, codon optimisation has become viable. Some organisms use Hoogsteen base pairing - expressing a protein from an organism that uses Watson-Crick pairing would require optimisation to ensure successful expression.
Why are there codon biases?
The genetic code of specific organisms is skewed towards specific codons - how this arose is subject to dispute. Codon usage and tRNA expression may have co-evolved to give feedback between the two. This essentially involves high levels of one codon driving up the expression of its corresponding tRNA, or high levels of a tRNA favouring the expression of its codon.3
Some codons are translated much more accurately and efficiently, favouring their use in the genome.4 However, it could be advantageous to use uncommon codons in some protein domains - for instance in areas that require a slowdown to fold correctly. Here, a rare codon could be included to slow translation down and allow the domains to fold correctly.4
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