Fig. 11. A model for the evolution of STATs and their DNA binding sites. The model proposes an ancestral, constitutively dimeric protein (GAA). It has a GAA-binding half site and binds DNA co-operatively. This latter feature favoured the evolution of tandem, dyad-binding sites of the form (GAAnTTC)n. The junctions between these sites (shown at A) constitute potential binding sites for a protein recognising the reversed order sequence TTCnGAA. STAT proteins are proposed to have arisen, by the recruitment of a site of tyrosine phosphorylation (Y) and an SH2 domain (SH2), to bind such junctional sequences.