Evolution of dimeric protein interfaces after gene duplication

Abstract

A significant number of proteins function as multimeric structures, most commonly as dimers. One of the primary mechanisms by which proteins evolve is through gene duplication and mutations of the resulting duplicated gene. The evolution of dimeric proteins after gene duplication is of interest because it can form three types of dimer: two homodimers and a heterodimer. Point mutations that occur in the interface of dimers would affect their binding strength and might change their path in the evolution. Here we designed an evolutionary model for protein dimerization after gene duplication. In this work, we have used dimers' PDB structures to construct the network of contacts between amino acids in the interface. Several pairwise energy contact matrices were examined to find reasonable interface binding energies. Using the population genetics theory, we defined a selection criteria based on dimer interface strength and let them evolve as the mutations happen. We observed that the dimer structures are bound to be in the mostly homodimer state or mostly heterodimer state, and there are few occasions that we have all three types of structures as strong dimers. We anticipate three fates for the dimer protein's evolution after gene duplication, neofunctionalization, subfunctionalization, and loss of the gene. A loss of function in homodimer structures might eventually lead to a subfunctionalization since the two interfaces are different. On the other hand, if a heterodimer loss happens, we would have two strong homodimer structures so both neofunctionalization and subfunctionalization might still happen. In the first case, one could gain a new function while the other homodimer performs the protein's old function. In the latter case, the two separate homodimers could each assume different parts of the full function of the original gene (which is the definition of subfunctionalization).