Phylogenetic Incongruence among Oncogenic Genital Alpha Human Papillomaviruses

Abstract

The human papillomaviruses (HPVs) have long been thought to follow a monophyletic pattern of evolution with little if any evidence for recombination between genomes. On the basis of this model, both oncogenicity and tissue tropism appear to have evolved once. Still, no systematic statistical analyses have shown whether monophyly is the rule across all HPV open reading frames (ORFs). We conducted a taxonomic analysis of 59 mucosal/genital HPVs using whole-genome and sliding-window similarity measures; maximum-parsimony, neighbor-joining, and Bayesian phylogenetic analyses; and localized incongruence length difference (LILD) analyses. The algorithm for the LILD analyses localized incongruence by calculating the tree length differences between constrained and unconstrained nodes in a total-evidence tree across all HPV ORFs. The process allows statistical evaluation of every ORF/node pair in the total-evidence tree. The most significant incongruence was observed at the putative high-risk (i.e., cancer-associated) node, the common oncogenic ancestor for alpha HPV species 9 (e.g., HPV type 16 [HPV16]), 11, 7 (e.g., HPV18), 5, and 6. Although these groups share early-gene homology, including high degrees of similarity among E6 and E7, groups 9 and 11 diverge from groups 7, 5, and 6 with respect to L2 and L1. The HPV species groups primarily associated with cervical and anogenital cancers appear to follow two distinct evolutionary paths, one conferred by the early genes and another by the late genes. The incongruence in the genital HPV phylogeny could have occurred from an early recombination event, an ecological niche change, and/or asymmetric genome convergence driven by intense selection. These data indicate that the phylogeny of the oncogenic HPVs is complex and that their evolution may not be monophyletic across all genes.Over the past 30 years, intense systematic sequencing efforts have resulted in the availability of full genomes for over 100 human papillomavirus (HPV) types. Several phylogenetic studies have emerged at various points during the accumulation of these data (4,5,15,27). Classification of types into gross categories, such as cancer-causing and non-cancer-causing or cutaneal and mucosal viruses, is possible, since most oncogenic types share a common ancestor, and most common ancestors radiate within an ecological niche (e.g., infection of skin) (27), but genomic classifications are not always straightforward. The evolutionary histories of genes can be incongruent, confounding sequence-based taxonomies, which can be discrepant with the paleontological history of the taxa (10, 11). Despite efforts spent on minimizing its effects (19), incongruence is also a sign of a gene's break with organismal evolutionary history, sometimes revealing recombination or periods of intense selection (10,20). The considerable collection of papillomavirus (PV) sequence data, coupled to its inherent genomic stability, provides an ideal system for analysis of the evolutionary history of individual PV open reading frames (OR...

Comparative Analysis of 19 Genital Human Papillomavirus Types with Regard to p53 Degradation, Immortalization, Phylogeny, and Epidemiologic Risk Classification

“…A second cluster in the E6 tree (37) contained all known low-risk types, including HPV6, 11, 42, 44, and 54, and a distant branch contained HPV61 together with HPV72, 83, and 89. A very similar pattern was described when complete genomes were used (6,38), where high-risk types were found in species a5 (including HPV82), a6 (including HPV53), a7 (including HPV70), and a9, whereas low-risk types belong to a1, a3 (including HPV61), a10, and a13. Interestingly, this phylogenetic relationship reflects the ability of the different E6 proteins to induce p53 degradation in vitro and also the immortalization capabilities of the full-length viral genomes as shown by us and others before (8-11, 13, 14).…”

“…Risk classification: À, undetermined. The last row shows the phylogenetic classification of HPV genomes (6,38). Abbreviations: H, high risk; PH, possible high risk; L, low risk; C, carcinogenic; PC, possibly carcinogenic.…”

Isolation and genomic characterization of the first Norway rat (Rattus norvegicus) papillomavirus and its phylogenetic position within Pipapillomavirus, primarily infecting rodents

“…PVs are specific to their hosts and are generally considered to have co-diverged closely with mammals and other vertebrates (Van Ranst et al, 1995;Bernard et al, 2006). However, other evolutionary mechanisms such as recombination (Narechania et al, 2005;Varsani et al, 2006) and infection across species borders ('zoonosis'; Myers et al, 1996;Gottschling et al, 2007a) may contribute to their diversification (Gottschling et al, 2007b).…”

“…In the past years, phylogenetic analytical methods have been applied more rigorously for the reconstruction of PV evolution (García-Vallvé et al, 2005;Narechania et al, 2005;Rector et al, 2007). Four PV supertaxa have been identified, namely a+o-, b+c+p+j-, d+e-and k+l+m+n+s-PVs (Gottschling et al, 2007b), and most known PV types can be classified into one of them.…”

siRNA screening of the kinome identified Aurora A kinase as a therapeutic target gene in cervical cancer

“…Firstly, the lowrisk 1 group mainly includes HPVs which cause benign genital warts and oral lesions (Schiffman et al, 2005). Second, low-risk 2 HPVs are responsible for benign vaginal cells (Narechania et al, 2005). Finally, high-risk alpha-HPV, may result in cervical neoplasia and cancer (Castle et al, 2007).…”