Selection on codon bias

In a wide variety of organisms, synonymous codons are used with different frequencies, in a phenomenon known as codon bias. In an article just published in the Annual Review of Genetics, Ruth and Dmitri discuss the current understanding of the ways in which natural selection participates in the creation and maintenance of codon bias. We also raise several open questions: (i ) Is natural selection on codon bias always weak as suggested by a number of studies or is it weak only at equlibrium? (ii ) What determines the identity of the selectively optimal codons? (iii ) How do shifts in the identity of optimal codons take place? (iv) What is the exact nature of selection on codon bias?