Comparative analysis estimates the relative frequencies of co-divergence and cross-species transmission within viral families

Geoghegan, Jemma L.; Duchêne, Sebastián; Holmes, Edward C.

where T 1 and T 2 are the clades contained within the host and virus trees, respectively. Let the expression T 1 \ T 2 denote the clades that are shared between both trees so that (T 1 \ T 2 ) 0 corresponds to the clades that are not shared between the pair (i.e. those that are unique to each tree). The actual PH85 distance is twice the number of unique clades. To normalize this metric we divide PH85 by the maximum distance by considering the two tree topologies, randomizing the tips for one of the trees 1000 times, and calculating PH85 for each replicate (where 1000 randomizations was shown to be robust even for very large trees; see S2 Fig) . The largest value of the 1000 randomizations is approximately the maximum PH85 distance in tree topologies. Therefore, nPH85 ranges between 0, for identical trees, and 1, for trees that have no clades in common (Fig 1) . The advantages of this method over other tree distance metrics is that it is comparable for pairs of trees with different numbers of tips, it maintains the backbone of the tree (i.e. the tree structure remains constant, unlike in [46] ), and it is comparable for trees with polytomous nodes. To address phylogenetic uncertainty, we collapsed all nodes with aLRT of less than 0.8, which corresponds to a false-positive rate of <0.1 [39] . In such cases, we randomly resolved the polytomies 100 times and calculated the nPH85. Accordingly, we report the overall normalized topology distance, as well as the mean and 95% percentile range of values (S3 Table) .