African origin of polyomavirus JC and implications for prehistoric human migrations

The presence of distinctive types of JC virus (JCV) in the main ethnic groups suggests a close coevolution with the human host. However, phylogenetic trees of JCV show a basal clade of European lineages (Types 1/4), whereas trees of human genes are coherent in placing the first split between African and non-African populations. This discrepancy places into question the effectiveness of JCV as a marker of human population history. The present study investigates the evolution of JCV using a large set of fully sequenced strains. Their relationships are first elucidated by principal coordinates analysis. It is suggested that Type 6 from West Africa could represent the ancestral type, while the peculiar phylogeny of Types 1/4 could reflect their direct origin from the ancestral lineage. Further credit to the African origin of JCV is provided by a neighbor-joining analysis based on slow-evolving sites. Sequence analysis of fast-evolving sites reveals that the deep emergence of Types 1/4 in the tree does not reflect a real evolutionary divergence; rather it is the implicit result of a remarkably different G + C content. The hypothesis that Types 1/4 originated directly from Type 6 is confirmed by examining the pattern of variation at a few specific fast-evolving sites. On the basis of this approach, a twofold exit of JCV from Africa is hypothesized: one in the direction of the Eurasian continent and another limited to Europe. These findings suggest that two distinct migrations of individuals played a key role in the peopling of Europe during prehistoric times.