Evidence of recombination within human alpha-papillomavirus

Abstract

Background: Human papillomavirus (HPV) has a causal role in cervical cancer with almost half a million new cases occurring each year. Presence of the carcinogenic HPV is necessary for the development of the invasive carcinoma of the genital tract. Therefore, persistent infection with carcinogenic HPV causes virtually all cervical cancers. Some aspects of the molecular evolution of this virus, as the putative importance of recombination in its evolutionary history, are an opened current question. In addition, recombination could also be a significant issue nowadays since the frequency of co-infection with more than one HPV type is not a rare event and, thus, new recombinant types could be currently being generated.

Results: We have used human alpha-PV sequences from the public database at Los Alamos National Laboratory to report evidence that recombination may exist in this virus. A model-based population genetic approach was used to infer the recombination signal from the HPV DNA sequences grouped attending to phylogenetic and epidemiological information, as well as to clinical manifestations. Our results agree with recently published ones that use a different methodology to detect recombination associated to the gene L2. In addition, we have detected significant recombination signal in the genes E6, E7, L2 and L1 at different groups, and importantly within the high-risk type HPV16. The method used has recently been shown to be one of the most powerful and reliable procedures to detect the recombination signal.

Conclusion: We provide new support to the recent evidence of recombination in HPV. Additionally, we performed the recombination estimation assuming the best-fit model of nucleotide substitution and rate variation among sites, of the HPV DNA sequence sets. We found that the gene with recombination in most of the groups is L2 but the highest values were detected in L1 and E6. Gene E7 was recombinant only within the HPV16 type. The topic deserves further study because recombination is an important evolutionary mechanism that could have high impact both in pharmacogenomics (i.e. on the influence of genetic variation on the response to drugs) and for vaccine development.

Figure 1

HPV population recombination estimates under a gene conversion model assuming a Jukes-Cantor evolution model with 2 alleles. For each gene and from left to right: Bars with upper right lines: HPV-16. Empty bars: GI. Light shaded bar: GII. Bars with horizontal lines: GIII. *: Recombination test was significant.

Figure 2

HPV population recombination estimates under a gene conversion model with complex substitution models and rate variation among sites. For each gene and from left to right: Bars with upper right lines: HPV-16. Empty bars: GI. Light shaded bar: GII. Bars with horizontal lines: GIII. *: Recombination test was significant.