Fig. 5.

Cartoon showing two alternative pathways for generating the CARD1 and CARD2 domains and ultimately the MDA-5 and RIG-I proteins. (A) Dotted lines indicate fusion events that we infer from the CARD phylogenetic analysis in Fig. 3. Colors correspond to domain family labels in Fig. 4. This scenario suggests four fusion events, one each for the MDA-5 CARD1 and CARD2 boxes and the RIG-I CARD1 and CARD2 boxes. This scenario is less preferred because it infers one extra fusion event that cannot be supported by the phylogeny in Fig. 3. (B) This scenario suggests that MDA-5 and RIG-I CARD2 boxes have coevolved tightly after their fusion and before the duplication of MDA-5 and RIG-I whole genes. This scenario is less preferred because it suggests tight coevolution of CARD1 and CARD2 domains, which are clearly refuted by Table 1. Abbreviations: cdf, CARDif; csp, caspase. Solid black lines indicate duplication events.