We first identified the best-fitting substitution model for the HPeV sequences using the Modelgenerator package (GTR + Γ) [35] , and tested whether the evolution of the P1 and VP1 genetic regions was better described by a strict or relaxed lognormal molecular clock. A relaxed lognormal molecular clock provided a better fit to both datasets according to Bayes Factor (BF) analyses (P1: log 10 BF = 7.03 and VP1: log 10 BF = 27.8, Table 2 ). This is in accordance with significant rate variation among the branches of the inferred phylogeny as measured by a non-zero coefficient of variation (σ r ) obtained with the relaxed molecular clock analysis (P1: σ r = 0.29; VP1: σ r = 0.41) (see Methods for details). Using the available P1 and VP1 dated sequences of HPeV, our analysis inferred a similar rate of nucleotide substitution for both regions (P1 median: 2.21 × 10 -3 s/s/y, 95% HPD [0.48 × 10 -3 , 4.21 × 10 -3 ]; VP1 Table 2 ). The higher rate indicated for the VP1 region is possibly related to its antigenic properties, perhaps reflecting a difference in the level of gene expression or mirroring the involvement of the VP1 capsid protein in the viral entry mediated by cellular integrins.