Evolutionary history of cotranscriptional editing in the paramyxoviral phosphoprotein gene

Douglas, Jordan; Drummond, Alexei J; Kingston, Richard L

The phosphoprotein gene of the paramyxoviruses encodes multiple protein products. The P, V, and W proteins are generated by transcriptional slippage. This process results in the insertion of non-templated guanosine nucleosides into the mRNA at a conserved edit site. The P protein is an essential component of the viral RNA polymerase and is encoded by a faithful copy of the gene in the majority of paramyxoviruses. However, in some cases, the non-essential V protein is encoded by default and guanosines must be inserted into the mRNA in order to encode P. The number of guanosines inserted into the P gene can be described by a probability distribution, which varies between viruses. In this article, we review the nature of these distributions, which can be inferred from mRNA sequencing data, and reconstruct the evolutionary history of cotranscriptional editing in the paramyxovirus family. Our model suggests that, throughout known history of the family, the system has switched from a P default to a V default mode four times; complete loss of the editing system has occurred twice, the canonical zinc finger domain of the V protein has been deleted or heavily mutated a further two times, and the W protein has independently evolved a novel function three times. Finally, we review the physical mechanisms of cotranscriptional editing via slippage of the viral RNA polymerase.