NIFAS: visual analysis of domain evolution in proteins

Motivation: Multi-domain proteins have evolved by insertions or deletions o f distinct protein domains. Tracing the history of a certain domain combina tion can be important for functional annotation of multi-domain proteins, a nd for understanding the function of individual domains. In order to analyz e the evolutionary history of the domains in modular proteins it is desirab le to inspect a phylogenetic tree based on sequence divergence with the mod ular architecture of the sequences superimposed on the tree. Result: A Java applet, NIFAS, that integrates graphical domain schematics f or each sequence in an evolutionary tree was developed. NIFAS retrieves dom ain information from the Pfam database and uses CLUSTAL W to calculate a tr ee for a given Pfam domain. The tree can be displayed with symbolic bootstr ap values, and to allow the user to focus on a part of the tree, the layout can be altered by swapping nodes, changing the outgroup, and showing/colla psing subtrees. NIFAS is integrated with the Pfam database and is accessibl e over the internet (http://www.cgr.ki.se/Pfam). As an example, we use NIFA S to analyze the evolution of domains in Protein Kinases C.