JC virus (JCV) is a double-stranded DNA polyomavirus co-evolving with humans since the time of their origin in Africa. JCV seems to provide new insights into the history of human populations, as it suggests an expansion of humans from Africa via two distinct migrations, each carrying a different lineage of the virus. A possible alternative to this interpretation could be that the divergence between the two lineages is due to selective pressures favouring adaptation of JCV to different climates, thus making any inference about human history debatable. In the present study, the evolution of JCV was investigated by applying correspondence analysis to a set of 273 fully sequenced strains. The first and more important axis of ordination led to the detection of 61 nt positions as the main determinants of the divergence between the two virus lineages. One lineage includes strains of types 1 and 4, the other strains of types 2, 3, 7 and 8. The distinctiveness of the Caucasian lineage (types 1 and 4), largely diffused in the northern areas of the world, was almost entirely ascribed to synonymous substitutions. The findings provided by the subsequent axes of ordination supported the view of an evolutionary history of JCV characterized by genetic drift and migration, rather than by natural selection. Correspondence analysis was also applied to a set of 156 human mitochondrial genome sequences. A detailed comparison between the substitution patterns in JCV and mitochondria brought to light some relevant advantages of the use of the virus in tracing human migrations.
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