Fig. 1.

Diagrammatic representation of two possible pathways for the creation of linked but divergent CARD domains. (A) Domain structure of MDA-5 and RIG-I. Red box, CARD1; blue box, CARD2; green box, helicase domain; purple box, DEAD/DEAH domain. The numbers represent amino acid positions. (B) (Left) A simple domain duplication event to produce two linked domains. In this scenario, the two domains would be expected to have similar evolutionary histories. (Right) A more complicated pathway where linked domains, produced by independent and divergent evolution (dotted lines) of duplicated domains originally not in linkage, fuse to form linked domains. This second scenario would produce domains with differing evolutionary histories.