Prediction of the Molecular Boundary and Evolutionary History of Novel Viral AlkB Domains Using Homology Modeling and Principal Component Analysis

AlkB (Alkylation B) proteins are ubiquitous among cellular organisms where they act to reverse the damage in RNA and DNA due to methylation. The AlkB protein family is so significant to all forms of life that it was recently discovered that an AlkB domain is encoded as part of the replicase (poly)protein in a small subset of single-stranded, positive-sense RNA viruses belonging to five families. Interestingly, these AlkB-containing viruses are mostly important pathogens of perennials such as fruit crops. As a newly identified protein domain in RNA viruses, the origin, molecular boundary of the viral AlkB domain as well as its function in viral replication and infection are unknown. The poor sequence conservation of this domain has made traditional bioinformatic approaches unreliable and inconclusive. Here we apply principal component analysis, homology modelling, and traditional sequence based techniques to propose a molecular boundary and function to this novel viral domain.