Rooting human parechovirus evolution in time

Abstract

Background: The Picornaviridae family contains a number of important pathogenic viruses, among which the recently reclassified human parechoviruses (HPeVs). These viruses are widespread and can be grouped in several types. Understanding the evolutionary history of HPeV could answer questions such as how long the circulating lineages last shared a common ancestor and how the evolution of this viral species is shaped by its population dynamics. Using both strict and relaxed clock Bayesian phylogenetics we investigated 1) the substitutions rates of the structural P1 and capsid VP1 regions and 2) evolutionary timescale of currently circulating HPeV lineages.

Results: Our estimates reveal that human parechoviruses exhibit high substitution rates for both structural P1 and capsid VP1 regions, respectively 2.21 x 10(-3) (0.48 - 4.21 x 10(-3)) and 2.79 x 10(-3) (2.05 - 3.66 x 10(-3)) substitutions per site per year. These are within the range estimated for other picornaviruses. By employing a constant population size coalescent prior, the date of the most recent common ancestor was estimated to be at around 1600 (1427-1733). In addition, by looking at the frequency of synonymous and non-synonymous substitutions within the VP1 gene we show that purifying selection constitutes the dominating evolutionary force leading to strong amino acid conservation.

Conclusion: In conclusion, our estimates provide a timescale for the evolution of HPeVs and suggest that genetic diversity of current circulating HPeV types has arisen about 400 years ago.

Figure 1

Bayesian time-scaled phylogeny of HPeV based on VP1 sequence analysis. Maximum clade credibility tree obtained with BEAST with a constant size coalescent prior showing lineage splitting events (nodes A-F) since the most recent common ancestor to the presently circulating HPeV types. The divergence times correspond to the mean posterior estimate of their ages (in years). For the TMRCA, the correspondent 95% Bayesian credible intervals are shown (median 1600). Time axis is shown in years and ranges from the TMRCA to the present year. Deeper and some subtype nodes with posterior probability of higher than 0.8 are pointed out. Each colour corresponds to a specific HPeV, as indicated in the box on the right. The dashed grey circle depicts the extent of genetic diversity of the sampled HPeV strains. HPeV-1-"Harris-like" strains (*) clustered separately from the contemporary HPeV-1.

Figure 2

The dN/dS ratios per site in VP1 region of HPeV. Rate of nonsynonymous-to-synonymous substitutions per codon site across the VP1 region of the HPeV genome. The only amino acid likely prone to molecular adaptation (dN/dS > 1.0) at position 202 does not have sufficient statistical support (see also additional file 7).