Papillomavirus subtypes are natural and old taxa: phylogeny of human papillomavirus types 44 and 55 and 68a and -b

Abstract

A human papillomavirus (HPV) type is defined as an HPV isolate whose L1 gene sequence is at least 10% different from that of any other type, while a subtype is 2 to 10% different from any HPV type. In order to analyze the phylogeny behind the subtype definition, we compared 49 isolates of HPV type 44 (HPV-44) and its subtype HPV-55, previously misclassified as a separate type, and 41 isolates of the subtype pair HPV-68a and -b, sampled from cohorts in four continents. The subtypes of each pair are separated by deep dichotomic branching, and three of the four subtypes have evolved large phylogenetic clusters of genomic variants forming a "star" phylogeny, with some branches specific for ethnically defined cohorts. We conclude that subtypes of HPV types are natural and old taxa, equivalent to types, which either diverged more recently than types or evolved more slowly.

FIG. 1.

(A) Phylogenetic tree of 49 isolates of HPV-44 and its subtype HPV-55, which has been originally misclassified as an independent type and therefore numbered differently. The samples came from five cohorts of patients living in Sao Paulo, Brazil (BR), Hong Kong (HK), Monterrey, Mexico (MX), Cape Town, South Africa (SA), and Oklahoma City, Oklahoma (OK). The numerical codes following these abbreviations correlate to patients, whose identities remained unknown to the principal investigators of this study. The major phylogenetic tree was generated by the UPGMA (unweighted pair group method with arithmetic average) algorithm. The small inset was calculated by the neighbor-joining method and included in this figure to increase the visual impact of a star phylogeny as opposed to evolution by deep dichotomic branching.

FIG. 2.

Phylogenetic tree of 41 samples of HPV-68a and -b. Abbreviations and procedures were as described in the legend to Fig. 1. In addition to the samples from the above-named regions, there are samples from Edinburgh, Scotland (ED).