Fig 6. Proposed models for shared and distinct modes of adaptation for cGAS and OAS proteins in primates.

An ancestral protein (red) with template independent polymerase activity was challenged by pathogens (green), which led to gene duplications and divergence resulting in ancestral cGAS (blue) and ancestral OAS (yellow). cGAS and OAS likely faced shared and distinct inhibitors encoded by pathogens (colored hexagons). Extensive positive selection of cGAS and OAS resulted in a variety of substitutions that evade inhibition by pathogens. For cGAS, sampling of amino acid substitutions on protein surfaces (gray stars) and the expression of spliceforms that may produce molecular mimics or cGAS variant proteins that evade antagonism could provide diverse mechanisms of escape from pathogen-encoded inhibitors. Some OAS genes also fix amino acid substitutions (gray stars) and may also evade pathogens via duplications and gene fusion events evident in OAS2 and OAS3.