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Early mesozoic coexistence of amniotes and hepadnaviridae.

Suh A, Weber CC, Kehlmaier C, Braun EL, Green RE, Fritz U, Ray DA, Ellegren H - PLoS Genet. (2014)

Bottom Line: Notably, the organization of overlapping genes as well as the structure of elements involved in viral replication has remained highly conserved among HBVs along that time span, except for the presence of the X gene.We provide multiple lines of evidence that the tumor-promoting X protein of mammalian HBVs lacks a homolog in all other hepadnaviruses and propose a novel scenario for the emergence of X via segmental duplication and overprinting of pre-existing reading frames in the ancestor of mammalian HBVs.Our study reveals an unforeseen host range of prehistoric HBVs and provides novel insights into the genome evolution of hepadnaviruses throughout their long-lasting association with amniote hosts.

View Article: PubMed Central - PubMed

Affiliation: Department of Evolutionary Biology (EBC), Uppsala University, Uppsala, Sweden.

ABSTRACT
Hepadnaviridae are double-stranded DNA viruses that infect some species of birds and mammals. This includes humans, where hepatitis B viruses (HBVs) are prevalent pathogens in considerable parts of the global population. Recently, endogenized sequences of HBVs (eHBVs) have been discovered in bird genomes where they constitute direct evidence for the coexistence of these viruses and their hosts from the late Mesozoic until present. Nevertheless, virtually nothing is known about the ancient host range of this virus family in other animals. Here we report the first eHBVs from crocodilian, snake, and turtle genomes, including a turtle eHBV that endogenized >207 million years ago. This genomic "fossil" is >125 million years older than the oldest avian eHBV and provides the first direct evidence that Hepadnaviridae already existed during the Early Mesozoic. This implies that the Mesozoic fossil record of HBV infection spans three of the five major groups of land vertebrates, namely birds, crocodilians, and turtles. We show that the deep phylogenetic relationships of HBVs are largely congruent with the deep phylogeny of their amniote hosts, which suggests an ancient amniote-HBV coexistence and codivergence, at least since the Early Mesozoic. Notably, the organization of overlapping genes as well as the structure of elements involved in viral replication has remained highly conserved among HBVs along that time span, except for the presence of the X gene. We provide multiple lines of evidence that the tumor-promoting X protein of mammalian HBVs lacks a homolog in all other hepadnaviruses and propose a novel scenario for the emergence of X via segmental duplication and overprinting of pre-existing reading frames in the ancestor of mammalian HBVs. Our study reveals an unforeseen host range of prehistoric HBVs and provides novel insights into the genome evolution of hepadnaviruses throughout their long-lasting association with amniote hosts.

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Related in: MedlinePlus

Phylogeny of Hepadnaviridae and their amniote hosts.(A) Plotting the HBV endogenization events (red boxes) reconstructed in this study and ref. [10] on a dated [40] consensus phylogeny of amniotes [27], [30] suggests temporary Mesozoic coexistence of Hepadnaviridae with birds, crocodilians, and turtles, respectively. Extant coexistence with birds and mammals is denoted by green boxes and the undated evidence for snake HBV endogenization events is indicated by a dashed box. The rooted (A) and unrooted (B) phylograms (see S4 Figure for phylograms including the short fragments of eSNHBV1 and eSNHBV2) of a maximum likelihood (ML) analysis of the polymerase protein from hepadnaviruses and reverse-transcribing outgroups (caulimoviruses, retroviruses and retrotransposons) exhibit a phylogenetic placement of crocodilian eHBVs that recapitulates the deep phylogeny of their amniote hosts. The precore/core protein ML phylogram (C) on the same ingroup sampling (plus eTHBV) topologically indicates a bird+crocodilian grouping, too, as well as an affinity of these HBVs to the turtle eHBV. Nevertheless, the resolution of the PreC protein on deep HBV relationships remains limited as suggested by low bootstrap support of some internodes and different topologies with regards to the outgroup (i.e., grouping them within Orthohepadnaviruses) as well as the branching order of avian eHBVs. ML bootstrap values are shown in % on respective nodes. Note the long internodes leading to non-avian eHBV branches; these further support the distinctiveness of the protein sequences of these ancient hepadnaviral lineages. All ML trees were generated via RAxML 7.4.7 [76] using the JTT+G model and 1000 bootstrap replicates.
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pgen-1004559-g003: Phylogeny of Hepadnaviridae and their amniote hosts.(A) Plotting the HBV endogenization events (red boxes) reconstructed in this study and ref. [10] on a dated [40] consensus phylogeny of amniotes [27], [30] suggests temporary Mesozoic coexistence of Hepadnaviridae with birds, crocodilians, and turtles, respectively. Extant coexistence with birds and mammals is denoted by green boxes and the undated evidence for snake HBV endogenization events is indicated by a dashed box. The rooted (A) and unrooted (B) phylograms (see S4 Figure for phylograms including the short fragments of eSNHBV1 and eSNHBV2) of a maximum likelihood (ML) analysis of the polymerase protein from hepadnaviruses and reverse-transcribing outgroups (caulimoviruses, retroviruses and retrotransposons) exhibit a phylogenetic placement of crocodilian eHBVs that recapitulates the deep phylogeny of their amniote hosts. The precore/core protein ML phylogram (C) on the same ingroup sampling (plus eTHBV) topologically indicates a bird+crocodilian grouping, too, as well as an affinity of these HBVs to the turtle eHBV. Nevertheless, the resolution of the PreC protein on deep HBV relationships remains limited as suggested by low bootstrap support of some internodes and different topologies with regards to the outgroup (i.e., grouping them within Orthohepadnaviruses) as well as the branching order of avian eHBVs. ML bootstrap values are shown in % on respective nodes. Note the long internodes leading to non-avian eHBV branches; these further support the distinctiveness of the protein sequences of these ancient hepadnaviral lineages. All ML trees were generated via RAxML 7.4.7 [76] using the JTT+G model and 1000 bootstrap replicates.

Mentions: Recent paleovirological studies on avian eHBVs suggest that extant avihepadnaviruses and orthohepadnaviruses exhibit relatively shallow branches within phylogenetic trees compared to the deep divergences among eHBVs [5], [10] (see also S3C Figure). This suggests a recent divergence of circulating viruses among each of these two HBV lineages, whereas their endogenous avian counterparts appear to be relics of several distantly related, ancient lineages [10], [18] with avihepadnaviruses being sister clade to one of them [10]. We reevaluated this by inferring the phylogenetic relationships based on Pol and PreC/C protein sequences of the non-avian eHBVs among Hepadnaviridae. In addition to full-length avian eHBVs and a dense sampling of extant HBVs, we included reverse-transcribing outgroups such as retroviruses, caulimoviruses, and retrotransposons. In phylogenetic trees of both Pol and PreC/C (Fig. 3B–C, S4A–C Figure), the avian eHBVs form ancient, unrelated lineages, but with an eZHBV_C+avihepadnaviruses clade in the Pol tree and an eBHBVs+avihepadnaviruses clade in the PreC/C tree. This reversal in branching order could be explained by interspecific viral recombination events, as have been observed in some extant HBV lineages [56], [57], but is more likely due to the very limited amount of phylogenetically informative characters in the short PreC/C protein.


Early mesozoic coexistence of amniotes and hepadnaviridae.

Suh A, Weber CC, Kehlmaier C, Braun EL, Green RE, Fritz U, Ray DA, Ellegren H - PLoS Genet. (2014)

Phylogeny of Hepadnaviridae and their amniote hosts.(A) Plotting the HBV endogenization events (red boxes) reconstructed in this study and ref. [10] on a dated [40] consensus phylogeny of amniotes [27], [30] suggests temporary Mesozoic coexistence of Hepadnaviridae with birds, crocodilians, and turtles, respectively. Extant coexistence with birds and mammals is denoted by green boxes and the undated evidence for snake HBV endogenization events is indicated by a dashed box. The rooted (A) and unrooted (B) phylograms (see S4 Figure for phylograms including the short fragments of eSNHBV1 and eSNHBV2) of a maximum likelihood (ML) analysis of the polymerase protein from hepadnaviruses and reverse-transcribing outgroups (caulimoviruses, retroviruses and retrotransposons) exhibit a phylogenetic placement of crocodilian eHBVs that recapitulates the deep phylogeny of their amniote hosts. The precore/core protein ML phylogram (C) on the same ingroup sampling (plus eTHBV) topologically indicates a bird+crocodilian grouping, too, as well as an affinity of these HBVs to the turtle eHBV. Nevertheless, the resolution of the PreC protein on deep HBV relationships remains limited as suggested by low bootstrap support of some internodes and different topologies with regards to the outgroup (i.e., grouping them within Orthohepadnaviruses) as well as the branching order of avian eHBVs. ML bootstrap values are shown in % on respective nodes. Note the long internodes leading to non-avian eHBV branches; these further support the distinctiveness of the protein sequences of these ancient hepadnaviral lineages. All ML trees were generated via RAxML 7.4.7 [76] using the JTT+G model and 1000 bootstrap replicates.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4263362&req=5

pgen-1004559-g003: Phylogeny of Hepadnaviridae and their amniote hosts.(A) Plotting the HBV endogenization events (red boxes) reconstructed in this study and ref. [10] on a dated [40] consensus phylogeny of amniotes [27], [30] suggests temporary Mesozoic coexistence of Hepadnaviridae with birds, crocodilians, and turtles, respectively. Extant coexistence with birds and mammals is denoted by green boxes and the undated evidence for snake HBV endogenization events is indicated by a dashed box. The rooted (A) and unrooted (B) phylograms (see S4 Figure for phylograms including the short fragments of eSNHBV1 and eSNHBV2) of a maximum likelihood (ML) analysis of the polymerase protein from hepadnaviruses and reverse-transcribing outgroups (caulimoviruses, retroviruses and retrotransposons) exhibit a phylogenetic placement of crocodilian eHBVs that recapitulates the deep phylogeny of their amniote hosts. The precore/core protein ML phylogram (C) on the same ingroup sampling (plus eTHBV) topologically indicates a bird+crocodilian grouping, too, as well as an affinity of these HBVs to the turtle eHBV. Nevertheless, the resolution of the PreC protein on deep HBV relationships remains limited as suggested by low bootstrap support of some internodes and different topologies with regards to the outgroup (i.e., grouping them within Orthohepadnaviruses) as well as the branching order of avian eHBVs. ML bootstrap values are shown in % on respective nodes. Note the long internodes leading to non-avian eHBV branches; these further support the distinctiveness of the protein sequences of these ancient hepadnaviral lineages. All ML trees were generated via RAxML 7.4.7 [76] using the JTT+G model and 1000 bootstrap replicates.
Mentions: Recent paleovirological studies on avian eHBVs suggest that extant avihepadnaviruses and orthohepadnaviruses exhibit relatively shallow branches within phylogenetic trees compared to the deep divergences among eHBVs [5], [10] (see also S3C Figure). This suggests a recent divergence of circulating viruses among each of these two HBV lineages, whereas their endogenous avian counterparts appear to be relics of several distantly related, ancient lineages [10], [18] with avihepadnaviruses being sister clade to one of them [10]. We reevaluated this by inferring the phylogenetic relationships based on Pol and PreC/C protein sequences of the non-avian eHBVs among Hepadnaviridae. In addition to full-length avian eHBVs and a dense sampling of extant HBVs, we included reverse-transcribing outgroups such as retroviruses, caulimoviruses, and retrotransposons. In phylogenetic trees of both Pol and PreC/C (Fig. 3B–C, S4A–C Figure), the avian eHBVs form ancient, unrelated lineages, but with an eZHBV_C+avihepadnaviruses clade in the Pol tree and an eBHBVs+avihepadnaviruses clade in the PreC/C tree. This reversal in branching order could be explained by interspecific viral recombination events, as have been observed in some extant HBV lineages [56], [57], but is more likely due to the very limited amount of phylogenetically informative characters in the short PreC/C protein.

Bottom Line: Notably, the organization of overlapping genes as well as the structure of elements involved in viral replication has remained highly conserved among HBVs along that time span, except for the presence of the X gene.We provide multiple lines of evidence that the tumor-promoting X protein of mammalian HBVs lacks a homolog in all other hepadnaviruses and propose a novel scenario for the emergence of X via segmental duplication and overprinting of pre-existing reading frames in the ancestor of mammalian HBVs.Our study reveals an unforeseen host range of prehistoric HBVs and provides novel insights into the genome evolution of hepadnaviruses throughout their long-lasting association with amniote hosts.

View Article: PubMed Central - PubMed

Affiliation: Department of Evolutionary Biology (EBC), Uppsala University, Uppsala, Sweden.

ABSTRACT
Hepadnaviridae are double-stranded DNA viruses that infect some species of birds and mammals. This includes humans, where hepatitis B viruses (HBVs) are prevalent pathogens in considerable parts of the global population. Recently, endogenized sequences of HBVs (eHBVs) have been discovered in bird genomes where they constitute direct evidence for the coexistence of these viruses and their hosts from the late Mesozoic until present. Nevertheless, virtually nothing is known about the ancient host range of this virus family in other animals. Here we report the first eHBVs from crocodilian, snake, and turtle genomes, including a turtle eHBV that endogenized >207 million years ago. This genomic "fossil" is >125 million years older than the oldest avian eHBV and provides the first direct evidence that Hepadnaviridae already existed during the Early Mesozoic. This implies that the Mesozoic fossil record of HBV infection spans three of the five major groups of land vertebrates, namely birds, crocodilians, and turtles. We show that the deep phylogenetic relationships of HBVs are largely congruent with the deep phylogeny of their amniote hosts, which suggests an ancient amniote-HBV coexistence and codivergence, at least since the Early Mesozoic. Notably, the organization of overlapping genes as well as the structure of elements involved in viral replication has remained highly conserved among HBVs along that time span, except for the presence of the X gene. We provide multiple lines of evidence that the tumor-promoting X protein of mammalian HBVs lacks a homolog in all other hepadnaviruses and propose a novel scenario for the emergence of X via segmental duplication and overprinting of pre-existing reading frames in the ancestor of mammalian HBVs. Our study reveals an unforeseen host range of prehistoric HBVs and provides novel insights into the genome evolution of hepadnaviruses throughout their long-lasting association with amniote hosts.

Show MeSH
Related in: MedlinePlus