Schematic representation for the distribution of major groups of multidomain proteins containing GRX domains in the tree of life. The most ancient fusion appears to be that of GRX domains to pyridine nucleotide disulphide oxireductase domains because it is present in all kingdoms. TRX-GRX fusions may also have been present in the LCA (Latest Common Ancestor) of all three branches. Proteins standing at the end of a node are the ones identified in current organisms. Proteins standing on top of the branches of the tree and surrounded by upper and under lines that are dashed suggest when that type of protein may have first originated. All domains identified as unknown in the figure have not been identified in any of the available domain databases. All domains identified as PFAM in the figure have been identified in PFAM as associated to proteins of unknown function. Panel A – Non- TRX-GRX fusion proteins. Panel B – TRX-GRX fusion proteins. TRX-GRX fusion proteins exist in all three major branches of the tree of life. Duplication of the GRX domain appears to have occurred early in the eukaryotic life history. Some TRX-GRX proteins appear to have undergone two consecutive partial duplication/recombination events of the GRX domain after the initial TRX-GRX fusion. Distribution of TRX-GRX fusion proteins may result from a) multiple independent deletions of the TRX-GRX fusion in different bacterial branches and in the eukaryotic branch, followed by a new TRX-GRX fusion event in the eukaryotes (Scenario A, red lines), b) Two independent TRX-GRX fusion events, one in archaea and one in eukaryotes followed by horizontal gene transfer from archaea to bacteria (Scenario B, dashed mauve line), or c) TRX-GRX fusion originating in the ancestor of some bacterial lineages, followed by horizontal gene transfer to the ancestor of Archaea and an independent TRX-GRX fusion event in eukaryotes (Scenario C, dashed black line). See Discussion for further details.