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Diversifying selection in human papillomavirus type 16 lineages based on complete genome analyses
Zigui Chen1, Masanori Terai, Leiping Fu
1Department of Microbiology & Immunology, Albert Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Journal of Virology
|May 14, 2005
Summary
Human papillomavirus type 16 (HPV16) evolution reveals positive selection in E5 and E6 genes, crucial for cervical cancer. These findings offer insights into HPV16
Area of Science:
- Virology
- Genomics
- Molecular Evolution
Background:
- Human papillomavirus type 16 (HPV16) is a major cause of cervical cancer globally.
- Understanding HPV16 genetic variation is key to addressing its oncogenic potential.
Purpose of the Study:
- To analyze sequence variations across complete HPV16 genomes.
- To identify sites under selective pressure during HPV16 evolution.
Main Methods:
- Cloning and sequencing of 12 HPV16 isolates from cervicovaginal cells.
- Whole-genome comparative analysis against the HPV16R reference sequence.
- Application of maximum likelihood models for codon substitution analysis.
Main Results:
- 313 variable nucleotide positions (4.0%) and 243 variable amino acid positions (9.9%) were identified.
- Five codon sites in E5 and E6 open reading frames (ORFs) showed diversifying selective pressure.
- The E5 ORF exhibited the highest nonsynonymous/synonymous substitution rate (omega) ratio.
Conclusions:
- HPV16 E5 and E6 ORFs are evolving under positive Darwinian selection.
- This rapid evolution may be linked to HPV16's biological success and oncogenicity.
- Further research is needed to confirm the role of E5 and E6 selection in HPV16 pathogenesis.