Codon usage in unicellular organisms (and in _some_ multicellular ones) depends on two factors...mutational bias and translational selection. Optimal codons are those for which the isoaccepting tRNA species is present in great abundance. Usually a small subset of codons are 'optimal'. Whether the process is complex or not is probably subjective (i.e. what do you mean by 'complex')
It probably is complex (my interpretation). At the level of translation, highly expressed genes need to be translated quickly so that a new peptide can be synthesised again from the same mRNA. If the gene contains a lot of these 'optimal' codons then translation can proceed more quickly. The selective advantage conferred by an optimal codon is still EXTREMELY small. Unicellular organisms (and some bigger ones) have large population sizes, and so population genetics tells us that a small advantage like this may become important. For these highly expressed genes it may be large enough to be under selective pressure.
so here is the complex optimisation process.....translational selection acts on some codons so that if they appear in the gene (by random mutation), then they will become 'fixed' in the population (if the long-term effective population size is sufficiently large).
I still don't know if this is complex or not (any more complex than selective pressure stuff anywhere else)
> I am interested in codon bias as a combinatorial optimization
>problem...in some organisms, "optimal" codon usage appears to be
>correlated with the level of gene expression--highly expressed genes use
>the optimal codons whereas genes with lower expression use rare codons.
>Essentially, I am interested if this pattern results from a complex
>> Does anyone know of any articles on this issue?
Look up any papers by Paul M. Sharp or Andrew T. Lloyd or Dennis Shields or Ikemura (don't know the name) or Grantham or Wright
Hope this has served to be of some assistance,