One of the fundamental challenges in biology is to find the factors determining protein sequence evolution. Effort to find what determine protein sequence evolution is a process to give an answer to what make human different from other species, why and how humans or other species have such a set of proteins and which way each species is going to evolve further in the future under certain environment.
Up to now, several factors were found to be important to cause protein sequence evolution. These factors are gene expression level, protein sequence length, number of interaction partner, type of interaction partner, gene essentiality, designability and so on. Recently, structural characteristics of proteins are also recognized as an important factor in protein sequence evolution. Especially, impact of contact density and structural fold on evolutionary rate were studied.
Structural characteristics of proteins, especially for interface region, on protein evolution were more specifically studied in this article and several structural determinant of protein sequence evolution were found. First, the interfaces of protein-ligand and protein-protein were found to be evolved slowly compared to non-interface region. Second, the number of domains in a protein is found to be another important factor in protein sequence evolution regardless of contact density. Finally, the interfaces formed between different type of domain and different proteins evolved slowly.
These newly found structural characteristics could be helpful for more precise understanding of protein sequence evolution. This knowledge would be useful for accurate phylogenetic tree construction, genome-wide protein function prediction by measuring evolutionary rate, de novo protein design and modeling species evolution.