Two primary methods find use to date the time of viral subtype divergence. The most commonly employed approach determines the divergence time of subtypes using a molecular clock assumption (MCA) over an entire phylogeny [18, 21, 5, 26] . In its strict formulation, the MCA posits a proportional relation between the number of substitutions and the intervening time period over the entire phylogeny. Looser forms of MCAs require only that the proportionality hold along individual branches, with the rates across branches drawn from a pre-specified distribution [5] . Committed to some variant of the MCA, current algorithms then estimate the rate of nucleotide substitution over all taxa in a given set. Consequently, these methods provide inference most suitable for situations where sequence evolution follows a MCA (e.g. influenza A-H3N2 in human hosts, as in [9] ) or deviates from the MCA homogenously in time (e.g. perhaps influenza A in wild fowl, see [3] ). In considering divergence events between viral subtypes, even when the MCA well-approximates nucleotide substitution within a given subtype, the above methods may incorrectly infer the time of divergence across subtypes. By either assuming that a single rate of nucleotide substitution holds for the region preceding the common ancestor of each subtype or by smoothing the rate of nucleotide substitution over clades with different numbers of taxa, the adherence to a MCA prevents direct inference of the rate during subtype divergence. Suzuki and Nei (2002) propose an alternative, more heuristic method of estimation to counteract the problem of differing rates of substitution before and after zoonotic events [23, 25] . In these studies, the evolutionary models draw a distinction between the rate of substitution within a given subtype and the rate of substitution between subtypes. However, trouble arises since there are no methods for estimating the latter quantity. Consequently, the models assume that the rate of substitution for portions of the phylogeny between the subtypes equals the mean rate in the initial host species population. For instance, in dating the time of divergence between influenza B hemagglutinin and influenza C hemagglutinin-esterase, Suzuki and Nei use the rate of amino acid substitution for water fowl for the portions of the phylogeny previous to the TMRCA of these two proteins [23] . While this method may accurately reflect the rate within avian and human hosts, it neglects whatever additional changes in the rate of substitution are due to the process of zoonotic adaptation, likely leading to a substantial underestimation of the date of the TMRCA.