Full Genome and Individual Gene Analysis for Evolutionary Patterns of Locally Circulating Rabies Virus in Davao City

Abstract

Disease surveillance remains a challenge in the Philippines due to its limited resources. Integration of genomic-based surveillance in the National Rabies Control Program provides additional insights into rabies virus (RABV) evolution and transmission dynamics and can, therefore, inform public health decisions. This pilot study used the previously reported 49 RABV sequences in Davao City and some neighboring provinces to evaluate the utility of targeted sequencing as an inexpensive alternative to whole genome sequencing. We applied different tree distance metrics to compare RABV whole genome (WG) and individual RABV genes. Phylogenetic trees reconstructed using IQTree2 and BEAST were used to compare differences in phylogenetic signals, tree topology, and evolutionary patterns. There were no significant differences in the phylogenetic signals of the three major clades in the trees, with strong support values for sampling variance and underlying variances at the gene and site levels. A comparison of the Bayesian phylogenetic tree of WG and individual genes showed that there were no significant differences in the substitution rate and divergence time. Moreover, patristic distances (PDs) of all individual gene trees were positively correlated and congruent to the RABV WG of identical strains, with correlation values above 99%, which ruled out the possibility of missing out on relevant findings on evolutionary dynamics using only individual genes. Based on the results of our detailed genetic analyses, RNA-dependent RNA polymerase (L) and phosphoprotein (P) segments were identified as the best biomarkers to investigate the evolutionary analysis of locally circulating RABV variants in Davao City due to the close PDs of their trees relative to the WG. Less expensive options such as gene-based surveillance will enable the local government to trace and monitor the actual genetic diversity and spread of the virus, which could lead to the design and implementation of focused strategies.