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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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Non-avian hepatitis B paleovirus endogenization events.(A) Simplified chronogram of non-mammalian amniotes based on molecular dates of phylogenetic relationships among amniotes [40], squamate lepidosaurs [78], [79], turtles [39], birds [80], and crocodilians [42], [43]. Icosahedrons denote endogenization events, the asterisk indicates previously studied avian endogenizations [10], and the colored time axis corresponds to the International Stratigraphic Chart (http://www.stratigraphy.org/ICSchart/StratChart2010.pdf). All HBV EVE endogenization events were reconstructed based on their respective presence/absence patterns (“+”: presence, “−” absence; “?”: missing data or sequence could not be aligned). This is with the exception of cobra eSNHBVs where we could not ascertain presence/absence states in other squamates. The early Mesozoic eTHBV paleovirus (B) is present in orthologous locations in both pleurodiran and cryptodiran turtles, but absent in crocodilians. All crocodilians to the exclusion of the alligator (i.e., Longirostres [41]) share the Cretaceous eCRHBV1 insertion (C), while the Paleogene eCRHBV2 insertion (D) is present in saltwater and dwarf crocodile (i.e., Crocodylidae), but absent in orthologous positions in gharial and alligator. HBV-derived sequence residues are boxed.
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pgen-1004559-g001: Non-avian hepatitis B paleovirus endogenization events.(A) Simplified chronogram of non-mammalian amniotes based on molecular dates of phylogenetic relationships among amniotes [40], squamate lepidosaurs [78], [79], turtles [39], birds [80], and crocodilians [42], [43]. Icosahedrons denote endogenization events, the asterisk indicates previously studied avian endogenizations [10], and the colored time axis corresponds to the International Stratigraphic Chart (http://www.stratigraphy.org/ICSchart/StratChart2010.pdf). All HBV EVE endogenization events were reconstructed based on their respective presence/absence patterns (“+”: presence, “−” absence; “?”: missing data or sequence could not be aligned). This is with the exception of cobra eSNHBVs where we could not ascertain presence/absence states in other squamates. The early Mesozoic eTHBV paleovirus (B) is present in orthologous locations in both pleurodiran and cryptodiran turtles, but absent in crocodilians. All crocodilians to the exclusion of the alligator (i.e., Longirostres [41]) share the Cretaceous eCRHBV1 insertion (C), while the Paleogene eCRHBV2 insertion (D) is present in saltwater and dwarf crocodile (i.e., Crocodylidae), but absent in orthologous positions in gharial and alligator. HBV-derived sequence residues are boxed.

Mentions: We searched the recent saltwater crocodile, gharial, and American alligator draft genome assemblies [30], [32] using whole viral genomes of the duck HBV (DHBV; AY494851) and the Mesozoic avian eHBV (eZHBV_C [10]), and identified two endogenous crocodilian HBVs (eCRHBVs; Fig. 1A). Likewise, we screened the genomes of turtles (painted turtle, softshell turtles, and sea turtle [27], [28]), squamate lepidosaurs (cobra, boa, python, and anole lizard [29], [33], [34], [35]), and mammals (human, opossum, and platypus [36], [37], [38]) for the presence of eHBVs. We detected a single locus in turtle genomes, hereafter referred to as endogenous turtle HBV (eTHBV; Fig. 1A), two endogenous snake HBVs in the cobra genome (eSNHBVs; Fig. 1A), but no EVEs in the remaining squamate and mammalian genomes. Our presence/absence analyses show that all four available cryptodiran turtle genomes plus the sampled pleurodiran (side-necked) turtles (Mesoclemmys and Podocnemis) exhibit the eTHBV insertion, while it is absent in the orthologous position in crocodilian genomes (Fig. 1B). This suggests that it is of Triassic origin and was endogenized in the ancestor of Testudines that lived 207.0–230.7 MYA [39], [40]. eCRHBV1 (Fig. 1C) is present in all crocodilians except alligators (i.e., Longirostres [41]) and is 63.8–102.6 MY [42] old, i.e., of Cretaceous origin. The second crocodilian EVE (eCRHBV2) is exclusively shared between saltwater and dwarf crocodile; its endogenization thus occurred during the Paleogene in the ancestor of Crocodylidae (30.7–63.8 MYA [42], ). Unfortunately, the snake EVEs remain undated, as none of the cobra eSNHBV loci could be aligned to other squamate genomes for ascertainment of EVE presence/absence (Fig. 1A). Given the dense fossil record of crocodilians and turtles that provides multiple calibrations for molecular dating of species divergences [39], [42], we suggest that the aforementioned dates are robust age estimates of eCRHBV1, eCRHBV2, and eTHBV endogenizations. Furthermore, molecular dating studies using mitochondrial genomes [44], [45] or nuclear loci [42], [43] yielded similar results on crocodilian divergence times, and the basal turtle divergence time of 207 MYA [39], [46] (i.e., the Cryptodira–Pleurodira split) is a nuclear estimate that is well compatible with mitochondrial estimates [47], [48] and the fossil record [49].


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)

Non-avian hepatitis B paleovirus endogenization events.(A) Simplified chronogram of non-mammalian amniotes based on molecular dates of phylogenetic relationships among amniotes [40], squamate lepidosaurs [78], [79], turtles [39], birds [80], and crocodilians [42], [43]. Icosahedrons denote endogenization events, the asterisk indicates previously studied avian endogenizations [10], and the colored time axis corresponds to the International Stratigraphic Chart (http://www.stratigraphy.org/ICSchart/StratChart2010.pdf). All HBV EVE endogenization events were reconstructed based on their respective presence/absence patterns (“+”: presence, “−” absence; “?”: missing data or sequence could not be aligned). This is with the exception of cobra eSNHBVs where we could not ascertain presence/absence states in other squamates. The early Mesozoic eTHBV paleovirus (B) is present in orthologous locations in both pleurodiran and cryptodiran turtles, but absent in crocodilians. All crocodilians to the exclusion of the alligator (i.e., Longirostres [41]) share the Cretaceous eCRHBV1 insertion (C), while the Paleogene eCRHBV2 insertion (D) is present in saltwater and dwarf crocodile (i.e., Crocodylidae), but absent in orthologous positions in gharial and alligator. HBV-derived sequence residues are boxed.
© Copyright Policy
Related In: Results  -  Collection

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

pgen-1004559-g001: Non-avian hepatitis B paleovirus endogenization events.(A) Simplified chronogram of non-mammalian amniotes based on molecular dates of phylogenetic relationships among amniotes [40], squamate lepidosaurs [78], [79], turtles [39], birds [80], and crocodilians [42], [43]. Icosahedrons denote endogenization events, the asterisk indicates previously studied avian endogenizations [10], and the colored time axis corresponds to the International Stratigraphic Chart (http://www.stratigraphy.org/ICSchart/StratChart2010.pdf). All HBV EVE endogenization events were reconstructed based on their respective presence/absence patterns (“+”: presence, “−” absence; “?”: missing data or sequence could not be aligned). This is with the exception of cobra eSNHBVs where we could not ascertain presence/absence states in other squamates. The early Mesozoic eTHBV paleovirus (B) is present in orthologous locations in both pleurodiran and cryptodiran turtles, but absent in crocodilians. All crocodilians to the exclusion of the alligator (i.e., Longirostres [41]) share the Cretaceous eCRHBV1 insertion (C), while the Paleogene eCRHBV2 insertion (D) is present in saltwater and dwarf crocodile (i.e., Crocodylidae), but absent in orthologous positions in gharial and alligator. HBV-derived sequence residues are boxed.
Mentions: We searched the recent saltwater crocodile, gharial, and American alligator draft genome assemblies [30], [32] using whole viral genomes of the duck HBV (DHBV; AY494851) and the Mesozoic avian eHBV (eZHBV_C [10]), and identified two endogenous crocodilian HBVs (eCRHBVs; Fig. 1A). Likewise, we screened the genomes of turtles (painted turtle, softshell turtles, and sea turtle [27], [28]), squamate lepidosaurs (cobra, boa, python, and anole lizard [29], [33], [34], [35]), and mammals (human, opossum, and platypus [36], [37], [38]) for the presence of eHBVs. We detected a single locus in turtle genomes, hereafter referred to as endogenous turtle HBV (eTHBV; Fig. 1A), two endogenous snake HBVs in the cobra genome (eSNHBVs; Fig. 1A), but no EVEs in the remaining squamate and mammalian genomes. Our presence/absence analyses show that all four available cryptodiran turtle genomes plus the sampled pleurodiran (side-necked) turtles (Mesoclemmys and Podocnemis) exhibit the eTHBV insertion, while it is absent in the orthologous position in crocodilian genomes (Fig. 1B). This suggests that it is of Triassic origin and was endogenized in the ancestor of Testudines that lived 207.0–230.7 MYA [39], [40]. eCRHBV1 (Fig. 1C) is present in all crocodilians except alligators (i.e., Longirostres [41]) and is 63.8–102.6 MY [42] old, i.e., of Cretaceous origin. The second crocodilian EVE (eCRHBV2) is exclusively shared between saltwater and dwarf crocodile; its endogenization thus occurred during the Paleogene in the ancestor of Crocodylidae (30.7–63.8 MYA [42], ). Unfortunately, the snake EVEs remain undated, as none of the cobra eSNHBV loci could be aligned to other squamate genomes for ascertainment of EVE presence/absence (Fig. 1A). Given the dense fossil record of crocodilians and turtles that provides multiple calibrations for molecular dating of species divergences [39], [42], we suggest that the aforementioned dates are robust age estimates of eCRHBV1, eCRHBV2, and eTHBV endogenizations. Furthermore, molecular dating studies using mitochondrial genomes [44], [45] or nuclear loci [42], [43] yielded similar results on crocodilian divergence times, and the basal turtle divergence time of 207 MYA [39], [46] (i.e., the Cryptodira–Pleurodira split) is a nuclear estimate that is well compatible with mitochondrial estimates [47], [48] and the fossil record [49].

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