Such large numbers of nonsynonymous substitutions between orthologues is suggestive of adaptive selection. Analysis of sequence diversity of Tas2rs in humans, great apes and old world monkeys suggest that Tas2rs are subject to some degree of positive selection [43,44]. However, the fact that these two mouse strains, members of the same species, are so closely related makes this explanation problematic. It is possible that B6 and D2 mice, which have a similar origin in the early 20th century, inherited different Tas2r haplotypes present in wild mouse populations prior to inbreeding. Characterization of Tas2r sequences of several wild mouse species or subspecies, or in other inbred lines, would shed light on this issue.