EVOLUTION OF HUMAN PAPILLOMAVIRUS TYPE-18 - AN ANCIENT PHYLOGENETIC ROOT IN AFRICA AND INTRATYPE DIVERSITY REFLECT COEVOLUTION WITH HUMAN ETHNIC-GROUPS

Papillomaviruses are an ideal model system for the study of DNA virus evolution. On several levels, phylogenetic trees of papillomaviruses r eflect the relationship of their hosts. Papillomaviruses isolated from remotely related vertebrates form major branches. One branch of human papillomaviruses (HPVs) includes an ape and two monkey papillomavirus es, possibly because the diversification of the viruses predated the s eparation of the infected-primate taxa. This hypothesis predicts that the root of the evolution of some if not all HPV types should point to Africa, since humans evolved from nonhuman primates in this continent . We tested this hypothesis and compared the genomic sequences of HPV type 18 (HPV-18) isolates from four continents. Diversity within HPV-1 8 correlates with patterns of the evolution and spread of Homo sapiens : HPV-18 variants, just like HPV-16 variants, are specific for the maj or human races, with maximal diversity in Africa. Outgroup rooting of the HPV-18 tree against HPV-45, which is closely related to HPV-18, id entifies African HPV-18 variants at the root of the tree. The identifi cation of an African HPV-45 isolate further reduces the evolutionary d istance between HPV-18 and HPV-45. HPV-18 variants from Amazonian Indi ans are the closest relatives to those from Japanese and Chinese patie nts and suggest that a single point mutation in the phylogenetically e valuated genomic segment represents at least 12,000 years of evolution . We estimate that diversity within HPV-18 and probably within other H PV types evolved over a period of more than 200,000 years and that div ersity between HPV types evolved over several million years.