Testing a covariotide model of DNA substitution.

The concomitantly variable codons hypothesis of DNA substitution argues that at any time only a fraction of the codons in a gene are capable of accepting a mutation. However, as mutations are fixed at some positions in a gene, the sites that are potentially variable also change because of changed functional constraints. This hypothesis has been termed the "covarion" hypothesis or when the model is applied to nucleotides, the "covariotide" hypothesis. The covarion-covariotide model has proven to be remarkably difficult to test. Here I examine a covariotide hypothesis for 11 genes using a likelihood ratio test. I show that in nine of the genes examined a covariotide model provides a better explanation of the data than a model that does not allow constraints to change over time.