Proteins, the main cell machinery which play a major roll in nearly every cellular process, have always been a central focus in biology. We live in the post-genomic era, and inferring information from massive data sets is a steadily growing universal challenge. The increasing availability of fully sequenced genomes can be regarded as the “Rosetta Stone” of the protein universe, allowing the understanding of genomes and their evolution, just as the original Rosetta Stone allowed Champollion to decipher the ancient Egyptian hieroglyphics. In this review, we consider aspects of the protein domain architectures repertoire that are closely related to those of human languages and aim to provide some insights about the language of proteins.

SignificanceThe vast, mostly unknown protein universe can be explored by analyzing protein sequences as a string of domains. A broader coverage can be achieved when these domains, the essential blocks in protein evolution, are detected using sequence profiles. Using clustering to collapse redundant profiles into unique function words (UFWs), we find that over the years 2009–2016, the number of UFWs saturates while the number of sequences matched by a combination of two or more UFWs grows exponentially.