By searching for "codon usage bias" in the search bar available in this google group, you can find
this old post in the PAML discussion group that may help answer your query.
In addition, you may want to check option `CodonFreq` in the PAML documentation to decide which setting best fits your data. This option can enable different codon frequencies for different codons. If the species or genes are so different that the different sequences in the alignment have different frequencies (e.g., some sequences are AT-rich while other sequences are GC-rich), then one should not conduct codon-based analyses -- this may happen when the species are distantly related, and the sequences are very divergent.