Revisiting protein structure, function, and evolution in the genomic era

The expansion of genomic data, three-dimensional structures of proteins, and computing power continues to improve our understanding of the evolution of protein structure and function relationships. As of June 2016, publically available databases contain more than 60 million unique protein sequences that group into 16,295 protein families that adopt ∼1400 different three-dimensional folds. This data supports the exploration of evolutionary relationships on protein structure and function to answer a basic question - how do changes in gene sequence lead to alterations in protein structure and to the tailoring of biological and chemical function? This mini-review aims to provide a primer on the basics of protein structure, how evolution of sequence leads to diversity in protein structure and function, how these changes occur, and the role of domains in protein evolution. Understanding how to use the vast amount of sequence and structural information may also aid in assessing if changes in protein sequence and/or structure are relevant for safety assessments of new commercial biotechnology products.