JC virus evolution and its association with human populations

Abstract

The ubiquitous human polyomavirus JC (JCV) is a small double-stranded DNA virus that establishes a persistent infection, and it is often transmitted from parents to children. There are at least 14 subtypes of the virus associated with different human populations. Because of its presumed codivergence with humans, JCV has been used as a genetic marker for human evolution and migration. Codivergence has also been used as a basis for estimating the rate of nucleotide substitution in JCV. We tested the hypothesis of host-virus codivergence by (i) performing a reconciliation analysis of phylogenetic trees of human and JCV populations and (ii) providing the first estimate of the evolutionary rate of JCV that is independent from the assumption of codivergence. Strikingly, our comparisons of JCV and human phylogenies provided no evidence for codivergence, suggesting that this virus should not be used as a marker for human population history. Further, while the estimated nucleotide substitution rate of JCV has large confidence intervals due to limited sampling, our analysis suggests that this virus may evolve nearly two orders of magnitude faster than predicted under the codivergence hypothesis.

FIG. 1.

Phylogenetic tree of 333 JCV genomes inferred using a maximum likelihood approach. The tree is midpoint rooted, and clades are labeled with the range of host ethnicities found in the clade (designations are those submitted by the publishing author) followed by the subtype designation. Bootstrap values, calculated using 1,000 replicate NJ trees, are labeled for relevant nodes with >50% support.

FIG. 2.

Tanglegrams a to i of JCV (right) and human population (left) phylogenies (see Table 1; see Fig. S3 in the supplemental material).

FIG. 3.

Skyline plots estimated from Bayesian MCMC analyses of (A) 158 JCV genomes found in geographically diverse populations and (B) 158 human mtDNA sequences with a similar geographical distribution. A priori nucleotide substitution rates of 1.7 × 10⁻⁵ and 1.7 × 10⁻⁸ subs/site/year were specified, respectively, while all other parameters were allowed to vary. The black line shows the median estimate of Θ (N_e × g) throughout the given time period. The gray area gives the 95% HPD interval of these estimates.