"over the last few years it's also been clear that codon bias can be evolutionarily constrained. For a while, it mostly thought to be based on tRNA levels (basi

"over the last few years it's also been clear that codon bias can be evolutionarily constrained. For a while, it mostly thought to be based on tRNA levels (basically anticodons). However, it's been increasingly clear that there are other constraints to protein coding sequences than just the decoded protein sequence (aka the genetic code)." This is a much older question than the last few years -- it's one of those "evergreen" questions that's been around for almost as long as we've been able to do statistics on codon prevalence. You'll see hand-wavy explanations for differences in codon usage in really old textbooks. The tRNA one is a particularly old chestnut -- I think I read about that one in my first undergrad course on molecular biology.