Most molecular evolution is neutral. Done.
Codon usage bias
Codon usage bias refers to differences in the frequency of occurrence of synonymous codons in coding DNA. A codon is a series of three nucleotides (triplets) that encodes a specific amino acid residue in a polypeptide chain or for the termination of translation (stop codons).
There are 64 different codons (61 codons encoding for amino acids plus 3 stop codons) but only 20 different translated amino acids. The overabundance in the number of codons allows many amino acids to be encoded by more than one codon. Because of such redundancy it is said that the genetic code is degenerate. Different organisms often show particular preferences for one of the several codons that encode the same amino acid- that is, a greater frequency of one will be found than expected by chance. How such preferences arise is a much debated area of molecular evolution.
It is generally acknowledged that codon preferences reflect a balance between mutational biases and natural selection for translational optimization. Optimal codons in fast-growing microorganisms, like Escherichia coli or Saccharomyces cerevisiae (baker’s yeast), reflect the composition of their respective genomic tRNA pool. It is thought that optimal codons help to achieve faster translation rates and high accuracy. As a result of these factors, translational selection is expected to be stronger in highly expressed genes, as is indeed the case for the above-mentioned organisms. In other organisms that do not show high growing rates or that present small genomes, codon usage optimization is normally absent, and codon preferences are determined by the characteristic mutational biases seen in that particular genome. Examples of this are Homo sapiens (human) and Helicobacter pylori. Organisms that show an intermediate level of codon usage optimization include Drosophila melanogaster (fruit fly), Caenorhabditis elegans (nematode worm), Strongylocentrotus purpuratus (sea urchin) or Arabidopsis thaliana (thale cress).
Recall selection entails a cost of maintenance and cost of construction. Has anyone bothered to estimate how expensive (in terms of reproductive excess) it is to evolve and maintain codon bias? Or how about the cost of maintenance and construction of the duon code? How about any other difficulty?
Let us suppose then that there is no budget to pay the cost of construction and maintenance of codon bias or duon codes, then we might be forced to conclude evolution of codon bias and duon codes were non-Darwinian and hence neutral, and hence a random walk. But the problem is codon bias and duon codes by definition are non-random features of the genome and thus cannot be the product of the random walks of Kimura/Nei neutral evolution.
Thus selection can’t work, neither can neutral evolution. There is of course a third option. Just sayin. 🙂