Supplementary Figure 7: Top 50 predicted coevolving residue pairs in Tcf1 and Lef1 orthologs.
From: Tcf1 and Lef1 transcription factors establish CD8+ T cell identity through intrinsic HDAC activity
Ninety-eight Tcf1 or Lef1 protein sequences were retrieved from 56 species and used in direct coupling analysis (DCA). In the output heatmap, the axes show the residues in the 30 aa Tcf1 HDAC domain and their positions. Each colored square represents the coordinates of the top 50 co-evolved pairs predicted by DCA. The color shade represents the strength of direct co-evolution coupling as measured by the direct information (DI).
Note that co-evolution may also play a role in the divergence of Tcf1 and Lef1 from conventional HDACs (Fig. 7b). Many residues that have a high degree of conservation within HDACs are involved in potential co-evolution in Tcf1 and Lef1. Examples include:
1. L196: L196-Q192, L196-T193, L196-D195, L196-S206;
2. G198: G198-T193, G198-P194, G198-S201, G198-S206, G198-V214;
3. T203: T203-T213, T203-V214;
4. L221: L221-P217,L221-S218, L221-P219, L221-P220;
5. P219: P219-P217, P219-S218, P219-P220, P219-L221.
All these predicted co-evolving pairs are in the columns marked by green arrows.
