Challenges and obstacles related to solving the codon bias riddles

Dozens of papers have been written about the relationship between codon bias, transcript features and gene translation. Even though answering these questions may sound straightforward, apparently many of these studies seem to contradict each other. In the present article, I provide four major non-mutually exclusive explanations related to this issue: (i) there are dozens of related relevant variables with unknown causal relationships; (ii) various biases in the relevant experimental data; (iii) drawing conclusions from specific examples; and (iv) challenges in experimentally modifying one biological variable without affecting the system via multiple biological feedback mechanisms. Specifically, some of the contradictions can be settled when considering these four points and/or via a multidisciplinary approach. The discussion reported in the present article is also relevant to many other biological/medical questions/fields.