Phylodynamic analyses reveal rapid evolution of rubella virus

Rubella is an infection caused by rubella virus. Rubella virus belongs to the Togaviridae family and is a single stranded positive sense RNA virus of about 9,762 nucleotides. Rubella, once known as German Measles, causes an iconic red rash all over the body and the teratogenic congenital rubella syndrome in pregnant women. Due to Measles-Mumps-Rubella vaccination rates falling throughout the developed world and measles and mumps becoming resurgent, the evolution of rubella virus is important to study prior to its potential resurgence. The E1 gene of the rubella virus is responsible for interaction with the human immune system, and it is the antigen to which antibodies are formed. The evolutionary rate of E1 along with the full rubella genome was determined using phylodynamic analysis. Both the whole genome and the E1 gene were evolving in a clocklike manner, and the evolution of both were successfully analyzed with BEAST2 software. A difference between the best-fitting priors between the two datasets was the kind of molecular clock preferred: the whole genome was best fit by a relaxed molecular clock, while the E1 gene preferred the strict molecular clock. This difference had some impact on the results, with the estimated evolutionary rate for the E1 gene from the strict clock being lower than the whole genome, but still within the 95% highest posterior density range at 1.08 x 10-3 substitutions per site per year (ssy) while the whole genome had an evolutionary rate of 1.60 x 10-3 ssy with a 95% Highest Posterior Density (HPD) of 1.06 x 10-3 to 2.18 x 10-3 ssy. Reconducting the E1 analysis with a relaxed molecular clock resulted in a similar evolutionary rate as the whole genome of 1.51 x 10-3 ssy with a 95% HPD of 1.23 x 10-3 to 1.80 x 10-3 ssy. This is one of the first cases where there was a statistically significant difference in substitution rate (non-overlapping HPDs) between analyses of the same dataset calculated with different clock priors. The relaxed clock estimates of nucleotide substitution rate are higher than has been estimated for rubella virus in the past and agrees with the more rapid rate of evolution seen in a single decade in China. These results suggest that rubella evolves faster than expected, though it is not undergoing substantial positive selection, and that choice of clock model is a more significant determinant of substitution rate than previously considered.M.S.Includes bibliographical reference