Abstract: The “protein universe” refers to the collection of all natural protein sequences. In this conceptual representation, protein families and superfamilies are surrounded by dark areas seemingly unexplored by Nature. Due to large-scale genomic projects, there is an exponential increase in protein sequence information deposited and automatically annotated on the basis of homology to proteins of known function. However, the number of “hypothetical proteins” and “proteins of unknown function” is increasing proportionally. This can be due to the low sensitivity of the methods behind these efforts, but also due to the presence of sequences belonging to not hitherto described biological systems that populate “dark areas of the protein universe”. Shedding light into these cases is imperative to multiple life sciences branches, as they may allow us to better understand important unknown biological systems and develop new technologies in human health, biotechnology, bioremediation, and pharmaceutics.

 

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