Figure 4. Negative selection to maintain homomers also maintains heteromers.

(A) The duplication of a gene encoding a homomeric protein and the evolution of the complexes is simulated by applying mutations to the corresponding subunits A and B. Only mutations that would require a single nucleotide change are allowed. Stop codons are disallowed. After introducing mutations, the selection model is applied to complexes and mutations are fixed or lost. (B to F) The binding energy of the HMs and the HET resulting from the duplication of a HM (PDB: 1M38) is followed through time under different selection regimes applied on protein stability and binding energy. More positive values indicate less favorable binding and more negative values indicate more favorable binding. (B) Accumulation and neutral fixation of mutations. (C) Selection on both HMs while the HET evolves neutrally. (D) Selection on HM AA or (E) HM BB: selection maintains one HM while the HET and the other HM evolve neutrally. (F) Selection on HET while the HMs evolve neutrally. (E) Selection on HM AA or (F) HM BB: selection maintains one HM while the HET and the other HM evolve neutrally. Mean binding energies among replicates are shown in thick lines and the individual replicates are shown with thin lines. Fifty replicate populations are monitored in each case and followed for 200 substitutions. PDB structure 1M38 was visualized with PyMOL (Schrödinger LLC, 2015). The number of substitutions that are fixed on average during the simulations are shown in Supplementary file 2 Table S8.

Figure 4—figure supplement 1. Percentage of interaction motifs for SSDs, WGDs and the two types of WGDs.

The data is the same as shown in Figure 2 but all four possible HM and HM&HET motifs are shown. 1HM: shows one homomer only, 2HM: shows both homomers, 1HM&HET: shows one homomer and the heteromer and 2HM&HET: shows both homomers and the heteromer. The percentage of motifs of interaction for SSDs (yellow) and WGDs (blue) (left panel) and for homeologs (dark blue) and true ohnologs (light blue) (right panel). P-values are from Fisher’s exact tests.

Figure 4—figure supplement 2. Similar evolutionary trajectories are observed for six different PDB structures.

The binding energy of six HMs and HETs is followed through time under the same scenarios as shown in Figure 4. Panels shown in Figure 4 are highlighted with a gray background here.

Figure 4—figure supplement 3. Effect of changes in parameters on the observed evolution trajectories.

Simulations were run for different combinations of parameters controlling the efficiency of selection ($\beta$ and $N$) and the length of the simulations for PDB structure 1M38.

Figure 4—figure supplement 4. Single mutants have pleiotropic effects for HM and HET.

The observed effects of sampled single mutants on the HET are compared with their effects on HMs. Pearson's correlation coefficients are shown. Parameters used for $\beta$ and $N$ were 10 and 1000, respectively.