Venomous lineages experienced different selective forces as compared to non-venomous ones. A Toxicofera experienced different selection as compared to non-toxicoferan reptiles. aBSREL found evidence for diversifying selection (red branches) in 6 branches within toxicofera. Alsi, Alligator sinensis; Cewa, Celestus warreni; Euma, Eublepharis macularius; Gein, Gerrhonotus infernalis; H_susp, Heloderma suspectum; Laag, Lacerta agilis; Pesi, Pelodiscus sinensis; Vaac, Varanus acanthurus; Vagi, Varanus gilleni; Vagl, Varanus glauerti; Vagig, Varanus giganteus; Vain, Varanus indicus; Vako, Varanus komodoensis; Vame, Varanus mertens; Vami, Varanus mitchelli; Vapa, Varanus panoptes; Vasc, Varanus scalaris. B Like in reptiles, venomous mammals experienced different selective pressures as compared to non-venomous mammals. aBSREL found evidence of diversifying selection one branch (red) leading up to a Solenodon copy (but see Supplementary Figure 11). Ereu, Erinaceus europaeus; Sopa, Solenodon paradoxus; BLTx, Blarina toxin; Calu, Canis lupus; Oran, Ornithorhynchus anatinus. C MEME identified 24 sites (in red) in the reptilian SVL that have experienced positive selection. Most of these sites are on the surface (raw output in supplementary dataset 9 and 10). These observations are consistent with previous estimates of high selection on surface residues of toxin serine protease . D Unlike reptiles, however, only 10 sites on mammalian KLK1s showed evidence of positive selection, with a few on the surface.