Partial protein domains: evolutionary insights and bioinformatics challenges

Protein domains are generally thought to correspond to units of evolution. New research raises questions about how such domains are defined with bioinformatics tools and sheds light on how evolution has enabled partial domains to be viable.With the rapid expansion in the number of determined protein sequences - over 92 million in UniProt in March 2015 - an ever-increasing number of biologists are using bioinformatics tools for annotation of these sequences. One widely used strategy is to identify occurrences of Pfam families within the sequence of interest 1]. A Pfam family is a multiple sequence alignment of the occurrences of a particular domain both in different species and in different regions of the same protein. The concept underpinning Pfam is that proteins typically comprise one or more domains (regions), each of which is an evolutionary unit that generally has a well-defined biological function. A significant sequence similarity between a query protein and a Pfam family provides the basis for annotations. Two recent articles 2,3] in Genome Biology evaluate the implications of having the query sequence only matching part of a Pfam family, which is an intriguing finding, given that a Pfam family is considered to be an evolutionary unit.