Limits...
Molecular archeological evidence in support of the repeated loss of a papillomavirus gene

View Article: PubMed Central - PubMed

ABSTRACT

It is becoming clear that, in addition to gene gain, the loss of genes may be an important evolutionary mechanism for many organisms. However, gene loss is often associated with an increased mutation rate, thus quickly erasing evidence from the genome. The analysis of evolutionarily related sequences can provide empirical evidence for gene loss events. This paper analyzes the sequences of over 300 genetically distinct papillomaviruses and provides evidence for a role of gene loss during the evolution of certain papillomavirus genomes. Phylogenetic analysis suggests that the viral E6 gene was lost at least twice. Despite belonging to distant papillomaviral genera, these viruses lacking a canonical E6 protein may potentially encode a highly hydrophobic protein from an overlapping open reading frame, which we designate E10. Evolutionary pressure working on this alternative frame, may explain why, despite having lost the E6 open reading frame between 20 and 60 million years ago, evidence of an E6-like protein is conserved.

No MeSH data available.


Time calibrated phylogenetic tree of Gammapapillomavirus sequences.The evolutionary rate estimated for feline PVs26 was used to estimate the divergence time of the indicated nodes. Classification was based on1819. The asterisk (*) indicates that some members of this clade have not yet been officially recognized as members of the Gammapapilliomavirus genus. Support values and exact estimates (with 95% highest posterior density) for each node are presented in supplementary Table 2. The Gamma-6 species is highlighted in red. The tree and geological column were generated using the APE52, phyloch (available from http://www.christophheibl.de/Rpackages.html), and strap53 packages within R. The scale bar indicates millions of years before the present. The Gammapapillomavirus genus tree was rooted on CPV2 (indicated by arrowhead in Fig. 1).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5015084&req=5

f2: Time calibrated phylogenetic tree of Gammapapillomavirus sequences.The evolutionary rate estimated for feline PVs26 was used to estimate the divergence time of the indicated nodes. Classification was based on1819. The asterisk (*) indicates that some members of this clade have not yet been officially recognized as members of the Gammapapilliomavirus genus. Support values and exact estimates (with 95% highest posterior density) for each node are presented in supplementary Table 2. The Gamma-6 species is highlighted in red. The tree and geological column were generated using the APE52, phyloch (available from http://www.christophheibl.de/Rpackages.html), and strap53 packages within R. The scale bar indicates millions of years before the present. The Gammapapillomavirus genus tree was rooted on CPV2 (indicated by arrowhead in Fig. 1).

Mentions: The members of the Gamma-6 species (HPV101, HPV103 and HPV108) do not encode a canonical E6 gene. Since all the other known members of the Gammapapillomavirus genus do contain such a gene, this suggests that the gene loss occurred in the most recent common ancestor of the Gamma-6 species. Likewise, this genetic event must have occurred after the Gamma-6 viruses diverged from the other members of the Gammapapillomavirus genus. Following the acquisition of an inactivating mutation, the lack of evolutionary selection will be manifested by the functional gene getting erased from the genome. Therefore, evidence for gene-loss can only be detected if viral species diverged in the relatively recent past. The evolutionary rate for papillomavirus has been estimated to be around 5–10 times faster than that of the host26. These published rate estimates were used to calculate the divergence times of members of the Gammapapillomavirus clade (Fig. 2). This analysis indicates that the gamma-6 species last shared a common ancestor with other Gammpapillomaviruses around 60 million years ago (node 2 in Fig. 2, and supplementary Table 1), while the MRCA of the current Gamma-6 viruses speciated around 23.4 MYA (node 3 in Fig. 2, and supplementary Table 2). Therefore, we hypothesize that the E6 ORF was lost from the Gamma-6 species between 20 and 60 MYA ago. This implies that the loss of E6 occurred following the emergence of the Simiiformes, but prior to the speciation event that gave rise to the Hominoidea (81 MYA to 20 MYA, respectively28). This implies that E6-minus viruses may infect both old-world and new-world monkeys. The isolation of more primate E6-minus viruses will be required to improve on these estimates, and confirm the presence of E6-minus viruses in new-world monkeys. The loss of the E6 protein from the Gamma-6 species was previously estimated to have occurred between 15–30 MYA29. This estimate was based on the L1 ORF of nine evolutionary highly divergent papillomaviruses (including an avian papillomavirus). Chen and colleagues estimated the divergence between the avian and mammalian viruses to have occurred around 50 MYA, while the respective hosts likely diverged about 300 MYA ago30. It is likely that the limited number of highly divergent sequences used resulted in an underestimation of the real evolutionary history of these ancient viruses. Furthermore, the evolution of papillomaviruses likely included ancient duplication events, further complicating analysis over long evolutionary distances1331.


Molecular archeological evidence in support of the repeated loss of a papillomavirus gene
Time calibrated phylogenetic tree of Gammapapillomavirus sequences.The evolutionary rate estimated for feline PVs26 was used to estimate the divergence time of the indicated nodes. Classification was based on1819. The asterisk (*) indicates that some members of this clade have not yet been officially recognized as members of the Gammapapilliomavirus genus. Support values and exact estimates (with 95% highest posterior density) for each node are presented in supplementary Table 2. The Gamma-6 species is highlighted in red. The tree and geological column were generated using the APE52, phyloch (available from http://www.christophheibl.de/Rpackages.html), and strap53 packages within R. The scale bar indicates millions of years before the present. The Gammapapillomavirus genus tree was rooted on CPV2 (indicated by arrowhead in Fig. 1).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5015084&req=5

f2: Time calibrated phylogenetic tree of Gammapapillomavirus sequences.The evolutionary rate estimated for feline PVs26 was used to estimate the divergence time of the indicated nodes. Classification was based on1819. The asterisk (*) indicates that some members of this clade have not yet been officially recognized as members of the Gammapapilliomavirus genus. Support values and exact estimates (with 95% highest posterior density) for each node are presented in supplementary Table 2. The Gamma-6 species is highlighted in red. The tree and geological column were generated using the APE52, phyloch (available from http://www.christophheibl.de/Rpackages.html), and strap53 packages within R. The scale bar indicates millions of years before the present. The Gammapapillomavirus genus tree was rooted on CPV2 (indicated by arrowhead in Fig. 1).
Mentions: The members of the Gamma-6 species (HPV101, HPV103 and HPV108) do not encode a canonical E6 gene. Since all the other known members of the Gammapapillomavirus genus do contain such a gene, this suggests that the gene loss occurred in the most recent common ancestor of the Gamma-6 species. Likewise, this genetic event must have occurred after the Gamma-6 viruses diverged from the other members of the Gammapapillomavirus genus. Following the acquisition of an inactivating mutation, the lack of evolutionary selection will be manifested by the functional gene getting erased from the genome. Therefore, evidence for gene-loss can only be detected if viral species diverged in the relatively recent past. The evolutionary rate for papillomavirus has been estimated to be around 5–10 times faster than that of the host26. These published rate estimates were used to calculate the divergence times of members of the Gammapapillomavirus clade (Fig. 2). This analysis indicates that the gamma-6 species last shared a common ancestor with other Gammpapillomaviruses around 60 million years ago (node 2 in Fig. 2, and supplementary Table 1), while the MRCA of the current Gamma-6 viruses speciated around 23.4 MYA (node 3 in Fig. 2, and supplementary Table 2). Therefore, we hypothesize that the E6 ORF was lost from the Gamma-6 species between 20 and 60 MYA ago. This implies that the loss of E6 occurred following the emergence of the Simiiformes, but prior to the speciation event that gave rise to the Hominoidea (81 MYA to 20 MYA, respectively28). This implies that E6-minus viruses may infect both old-world and new-world monkeys. The isolation of more primate E6-minus viruses will be required to improve on these estimates, and confirm the presence of E6-minus viruses in new-world monkeys. The loss of the E6 protein from the Gamma-6 species was previously estimated to have occurred between 15–30 MYA29. This estimate was based on the L1 ORF of nine evolutionary highly divergent papillomaviruses (including an avian papillomavirus). Chen and colleagues estimated the divergence between the avian and mammalian viruses to have occurred around 50 MYA, while the respective hosts likely diverged about 300 MYA ago30. It is likely that the limited number of highly divergent sequences used resulted in an underestimation of the real evolutionary history of these ancient viruses. Furthermore, the evolution of papillomaviruses likely included ancient duplication events, further complicating analysis over long evolutionary distances1331.

View Article: PubMed Central - PubMed

ABSTRACT

It is becoming clear that, in addition to gene gain, the loss of genes may be an important evolutionary mechanism for many organisms. However, gene loss is often associated with an increased mutation rate, thus quickly erasing evidence from the genome. The analysis of evolutionarily related sequences can provide empirical evidence for gene loss events. This paper analyzes the sequences of over 300 genetically distinct papillomaviruses and provides evidence for a role of gene loss during the evolution of certain papillomavirus genomes. Phylogenetic analysis suggests that the viral E6 gene was lost at least twice. Despite belonging to distant papillomaviral genera, these viruses lacking a canonical E6 protein may potentially encode a highly hydrophobic protein from an overlapping open reading frame, which we designate E10. Evolutionary pressure working on this alternative frame, may explain why, despite having lost the E6 open reading frame between 20 and 60 million years ago, evidence of an E6-like protein is conserved.

No MeSH data available.