○ The endosymbiont poc-like virus had no

Virus–Host Coevolution with a Focus on Animal and possibility for lytic cycle, thus it stated to
Human DNA Viruses replicate by means of cell-to-cell fusion
○ When 2 such cells (infected by related
Virus virus) fused to each other, viral DNA
was copied, and homologous viral
● Obligatory cellular parasites, developing with chromosomes formed tetrads
their hosts ● Cell division resulted in 4 daughter cells with one
● Coevolution copy of the endosymbiont virus in each
○ when the virus and the host affect each ○ Might be the origin of meiotic cell
other’s evolution division
● Red Queen Hypothesis Theory ● After its development, ​sexual reproduction
○ both the parasite and the host are offered a significant fitness advantage against
perpetually struggling to maintain any parasite
constant fitness level
Escaped Genes
Origin of Viruses: 3 Hypothesis ○ Mobile genetic elements escaped the cell
○ These elements acquired a protein capsid and
Primordial Virus World
started to replicate autonomously
○ Homologies can be observed among viral and
● Ancestors of viruses existed already in the
cellular genes
pre-cellular world
○ Root position and direction of evolution is
● Pre-cellular and pre-viral organisms competed
challenging to determine
with each other
■ E.g. cell and viral DNA polymerase are
● Evolution of viruses destroyed the possible
related but direction of viral DNA
signal of genetic relatedness
transfer is unknown
● Evidence:
Cellular Regression Theory
○ Existence of viral protein fold
○ Least favored theory
superfamilies without cellular
○ Viral genome is the remnant of a
counterparts
reduced cellular genome and capsid is
○ Proteins without any primary sequence
the cell membrane
homology are still grouped based on
○ Nucleo-cytoplasmic large DNA viruses
tertiary structure
(NCLDVs)
■ (e.g. the major capsid proteins
■ Proliferate in the cytoplasm
of PRD1 bacteriophage,
■ Have particle and genome sizes
adenoviruses, some archaeal
comparable to the small
viruses all have double jelly fold
prokaryotes
structure)
○ Modern version of the theory
○ Structural homologies in RNA- and
■ Viruses might be the reduced
DNA-dependent polymerases
descendants of pre-cellular
● Examples without cellular homologues:
Ur-organisms
○ Viral RNA-dependent RNA polymerase
■ Convert into obligatory cellular
are not homologous to their cellular
parasites
counterparts
● Viruses became obligatory parasites ​either​:
Viral Genetic Elements in Host Genomes
○ After the emergence of the last universal
● Polintons
common ancestor
○ Also known as Mavericks
○ They were already parasitizing on other
○ Mobile genetic elements with multiple
ancient replicators
homologues in the cellular and viral
● Viral eukaryogenesis hypothesis
genomes
○ Eukaryotic cell nucleus originated from
○ Have escaped several times and gave
an infection by a coated virus (became
rise to different viruses and mobile
an endosymbiont)
genetic elements
 ■ E.g. adenoviruses, ● 50% of the human
mitochondrial linear plasmids genome consist
○ These genetic elements are endogenous retroviral
homologous and related​, but direction of elements
genetic exchange is unknown ■ In prokaryotes, important
■ Common from host to virus and functions were attributed to
vice versa integrated viruses
● Endogenous Viral Elements (EVEs)
○ Viral genes or complete genomes Effects of the Bottleneck Phenomenon
inserted into host genomes ● Reduction of effective pop’n size due to
○ Most of the elements are of retroviral environmental events, for instance new habitat
origin, other virus families were also colonisation
detected ● Affects the virus-host coevolution: decreases
■ Hepadnaviruses both genetic variation and the fitness of the virus
■ Adeno-associated viruses ● Responsible for the founder effect
■ Herpesviruses ● Genetic Drift
○ If insertion occurs in the germ cell line, ○ Changes in genotype frequencies by
then inserted sequence stretch might stochastic pop’n size reduction
get inherited ● Occur during both intra- and inter-species steps
○ If the insertion provides a selective of the viral life cycle
advantage (e.g. protection from viral ● Multipartite viruses
infection), genomic change will be fixed ○ E.g. Plant infecting nanoviruses or
○ If advantage disappears, inserted animal-infecting bidnaviruses,
stretch might mutate over time and lose alphatetraviruses, nodaviruses and
its protective nature picobirnaviruses
○ Important sources for virus-host ○ Package their genetic material as
coevolutionary research independently encapsidated separate
○ Provide a map for viral host range segments
○ History of coevolution
■ Detection of homologous Antiviral Defence Mechanism
endogenous viral sequences in ● Shuttled Weapons
different host species ○ Superinfection exclusion
■ Provides information about ■ Integrated and expressed
historical host range of a virus endogenous viral protein
clade provides protection from
■ Can also be inferred based on exogenous infection
● Known diversification ■ First described in the tobacco
times of the host plant
● Or phylogenetic ■ Development was observed in
analyses of exo- and sheep & koalas
endogenous viral ■ Retroviral elements were
sequences endogenous in the genomes of
● E.g. endogenous sheep and koala, providing
lentiviral sequences in protection against certain
lemurs are said to be exogenous retroviral infections
coevolving with ○ CRISPR-Cas
primates ■ Bacterial antiphage system
○ Viruses represent a major force in ■ prokaryotic immune ​system​ that
evolutionary pressure confers resistance to foreign
■ Retroviruses are effective in genetic elements (google)
genome integration and ○ Argonaute proteins
coevolved with vertebrates
 ■ Show structural and functional Adenoviruses
homologies to retroviral ● DNA viruses, major capsid proteins of the
replication machinery non-enveloped, icosahedral capsid are the
■ Provide infection against hexon, penton base and protruding fibre,
invading nucleic acids in responsible for receptor binding
prokaryotes ● Infect ​vertebrate hosts​ and are clustered into 5
■ Similar with RNA interference accepted and one proposed genera
system of eukaryotes (does not ● Mastadenovirus and Aviadenovirus
have antiviral effect in ○ Infect mammals and birds respectively
chordates) ● Atadenoviruses
○ Endogenous retroviruses ○ Detected in reptiles, birds and ruminants
■ Provide transcription factor and a marsupial possum
binding sites for ○ Were isolated from cattle suggesting
interferon-stimulated genes some level of coevolution
○ Rag recombinases ● Siadenoviruses
■ Originate from transposons ○ In birds, a frog and a tortoise
found in genomes of starfish, ● Ichtadenovirus
oysters, and seas urchins ○ White sturgeon adenovirus
● Testadenoviruses
● Other Mechanisms ○ Most recently proposed
○ Antisense RNA ○ In testudinoid turtles
■ Most ancient defense ● Hypothesis started to evolve:​ adenoviruses
mechanism started to coevolve with the vertebrates, before
■ Gene translation of invading the divergence of fish from other vertebrates
pathogen is interfered by small ○ Mast-, avi-, at, si- and itchtadenovirus
complementary RNAs had been thought to coevolve with
○ Restriction Endonucleases mammals, birds, reptiles, amphibians
■ Cleaving the viral genome and fish respectively
○ Piwi-interacting RNA ● Thought to be host specific
■ Associate with nucleases and ○ Host changes did happen
provide defence against ○ E.g. 10 predicted host switches in the
transposable elements evolution of human adenoviruses
○ Engagement of pathogen-associated ■ Presumably a virus strain had
molecular patterns jumped to an ancient ruminant
■ Induces antiviral cytokines during evolutionary history
● Tumour necrosis factor ■ Atadenoviruses were isolated
in eukaryotes from cattle, sheep and mule
● Interleukins and deer, suggesting some level of
interferons in chordates coevolution
■ Activates natural killer cells ○ High genomic A + T content contradicts
○ APOBEC3 protein long cospeciation of these viruses
■ Part of the innate immune ● Non-reptile atadenovirus genomes have
system in humans 57-66.3% A + T content, while reptile
■ Targets specifically retroviruses atadenoviruses are not affected by such bias
and interferes with their reverse ○ It is hypothesized that longer
transcription coevolutionary times---adaptation of the
■ HIV counteracts this effect by virus to the host---result in a balanced
the viral infectivity factor nucleotide composition
● Triggers the ● Similar observations in pathology
degradation of ○ Generally cause mild disease and there
APOBEC3 are apathogenic strains at least in
healthy individuals
 ○ Not all serotypes of the species ​Fowl ■ HVs of molluscs
aviadenovirus D and E​ cause inclusion ● Putative ATPase subunit of terminase
body hepatitis in chicken ○ Most conserved gene of all known HVs
○ Recent host switches might result in an ○ Responsible for packaging of viral DNA
elevated pathogenicity in the capsid
○ The A + T content of the known genome ● HVs were also found in T4 bacteriophages
part is over 59% and from serologically (​Myoviridae​)
identical strains several fibre size ● Phylogenetic relationship is largely synchronous
variants were described with host lineages, except for mammals
○ Mutations might be consequences of an ● Major sublineages (​Alpha-, Beta-,
ongoing evolution Gammaherpesvirinae​) emerged before
■ Represent the adaptation to a mammalian radiation (60-80M years ago)
new host, cattle ● Subfamilies were found 200M years ago
● Most investigated adenoviruses are evidently ● Bovine herpesvirus 4 ​ (BoHV-4)
human and other primate adenoviruses. ○ Isolated from cattle and this species was
○ Most ancient lineages are the prosimian thought to be the original host of the
and New World monkey adenoviruses virus
○ Old world monkey adenoviruses and ○ Reported from wild buffalo and other
Human mastadenovirus (HAdV) A, F ruminants as well
and G ○ Original host might be the African
○ HAdV-B and -E are of gorilla or buffalo
chimpanzee origin respectively
○ HAdV-C seemingly codiverged with ● Herpesviridae
gorillas, chimpanzees, bonobos and ○ Primate cytomegalovirus genomes also
humans showed coevolution of virus and host
○ HAdV-D viruses infect only humans ○ Avian and reptilian HVs
● HAdV-D strains show that homologous ■ Clustered into subfamily
recombination has a driving force in adenovirus Alphaherpesvirinae
evolution ● Alloherpesviridae
○ Intraspecies recombination events are ○ Fish and amphibian HVs are put within
common the order ​Herpesvirales
○ Intergenus recombinatinants have also ○ Separation of the main alloherpesvirus
been reported lineages does not fully resemble that of
○ Recombination enables an accelerated the host taxa
modular evolution of viruses ■ Explanation: Diversion of the
ancestry of the viruses occurred
Herpesviruses (HVs) before the separation of fish
● Large (150-200 nm) icosahedral, enveloped lineages
viruses with a tegument layer between capsid ○ Strong similarity among viruses of
and envelope distantly related fish species could be
● Have linear, non-segmented DNA genome explained by host switches
● Known to infect all classes of vertebrates ● Integrated herpesviral genomes in host
● Also discovered in mollusc species chromosomes were discovered in the last years
● Tentatively classified under the family ○ Discovery of a new lineage of
Herpesviridae​ because of their morphological alloherpesviruses associated with at
features least 15 different fish species
● Herpesviridae w ​ as divided into 3 families in ■ Salmo salar (​ full-length viral
2009 genome in salmon)
○ Herpesviridae ○ HV genome integrated into the genome
■ Only the HVs of amniotes of invertebrate chordates
○ Alloherpesviridae ■ Links ancestors of mollusc and
■ HVs of amphibians and fish vertebrate HVs
○ Malacoherpesviridae
 ■ Branchiostoma floridae g ​ enome ■ Triggered the ​“fourth domain
(Florida lancelet/amphioxus) hypothesis”
shows homology to herpesviral ■ Giant viruses evolved from
genes cellular ancestors
● Terminase and ○ Multiple origin of viral gigantism
polymerase gene ■ Alternative hypothesis
sequences is highly ■ Three major branches on the
similar to the mollusc NCLDV tree
HV ■ At least three independent
emergences from smaller
Nucleo-cytoplasmic Large DNA Viruses (NCLDV) viruses
● Group of DNA viruses including families ○ For translation-related genes
○ Ascoviridae ■ Kinship between viral and
○ Asfarviridae eukaryotic lineages from
○ Iridoviridae phylogenetic analyses
○ Marseilleviridae ● Lateral gene transfers
○ Mimiviridae at different points of the
○ Pithoviridae virus evolution
○ Phycodnaviridae ● Further evolutionary
○ Poxviridae reconstructions reveal a
● Megavirales connection between
○ A new virus order that was proposed NCLDVs and smaller
○ Not yet accepted by the International eukaryotic viruses
Committee on Taxonomy of Viruses ● Derived from tailless
(ICTV) bacteriophages
● Hosts ranges from unicellular eukaryotes via ● Reconstructed phylogeny:
arthropods to vertebrates (mammals included) ○ Branch 1 (Real giants)
● Replicate within the cytoplasm of infected cells ■ Mimiviridae
○ Some families include a nuclear stage ■ Pandoraviruses
● Encode many genes required for a successful ○ Branch 2 (Varying genome sizes)
replication but uses the translational material of ■ Ascoviridae
the host ■ Iridoviridae
● Form a monophyletic group with a common ■ Marseilleviridae
ancestor ■ Pithoviridae
● First giant amoeba virus ○ Branch 3 (Non-giants)
○ Large compared to a normal virus size ■ Asfarviridae
(700 nm) ● African swine fever
○ Has a large genome virus
○ Contained several genes of distant ● Other protist-infecting
origins acquired by lateral gene transfer relatives
● Mimivirus ■ Poxviridae
○ Discovered in 2003 ● Host switch took place
○ Found to contain nearly all NCLDV core two times here
genes ● Coevolution took place
○ Clustered phylogenetically with which caused several
phycodnaviruses genera and poxvirus
○ An oversized NCLDV ‘types’
○ Translation system illustrated a ● Infected a wide range of
divergent evolutionary path arthropods and
○ Clustered on a distinct branch and vertebrates
separated from the three domains of cell ● Second host switch
life happened in sensu lato
asfarviruses
 ○ Infected protists ○ Also a feature of some Py V infections in
and pigs humans
● Phylogenetic reconstructions of NCLDVs ○ Mutations in early region can lead to
showed a turbulent evolution expression of a truncated form of the
○ Dominated by gene gain large tumour antigen
○ Substantial gene loss was shown in ● Rearrangements in non-coding control region in
other branches point mutations in VP1 have been described in 2
■ Giant protist viruses (gene important human PyVs:
gainers) ○ JCPy V
■ NCLDV animal infectors (gene ■ Mutations lead to development
loss by gene contraction) of progressive multifocal
● Hypothesis: selective leukoencephalopathy
pressure for virus ○ BKPy V
genome size is stronger ■ Non-coding control region
than in protists rearrangements play a direct
role in the development of Py V
Polyomaviruses (PyVs) associated nephropathy
● Non-enveloped icosahedral DNA tumour viruses ○ Therefore, intra-host viral evolution
with a double-stranded circular DNA genome appears to be an essential component
● Polyomaviridae to the disease process
○ Approximately 80 accepted Py V ● A recent host switch is usually associated with
species elevated pathogenic
○ 4 genera: (Alpha, Beta, Gamma, and ○ E.g. Closely related Py Vs can be
Deltapolyomavirus) detected in healthy bats, whereas the
○ Taxonomical classification is based on goose hemorrhagic polyomavirus infects
genetic distance of the large tumour geese, Muscovy ducks & murlards
antigen
● Circular Py V genome is highly conserved Circoviruses
○ 5-7 genes located on both strands ● Circoviridae
○ Non-coding region ● Vertebrate -infecting single stranded DNA
○ Early coding region contains regulatory (ssDNA) viruses with one of the smallest virus
proteins: small and large tumour antigen genomes
○ Late coding region contains genes of ○ Contains 2 genes (rep and cap)
the structural proteins (like major (VP1) encoding replication-associated (Rep)
and 2 minor capsid proteins) and the capsid (Cap) proteins
○ Non-coding region contains regulatory ○ Porcine circovirus 1
elements and transcription promoters ■ First recognised circovirus
● Known to infect mammals and birds, but uses infecting swine and wild boar
viral metagenomics ● Potential long-term adaptation of some
○ Also identified in fish and arthropods circovirus groups to birds, mammals, reptiles
● Py Vs have been coevolving with their shots for and fish
about half billion years ● Complete or partial circovirus genome might be
○ Current taxonomic classification does integrated into the host genome as an EVE
not reflect this coevolution ○ Rep- and cap- homologues have been
○ Some modern Py V species arose after detected in different animal genomes
ancient recombination events ○ Various possible functions (e.g. antiviral
○ Mammalian Py Vs are known to be protection)
host-specific and coevolving with their ● Theories:
hosts ○ Plant-infecting geminiviruses as the
○ Py Vs are generally apathogenic in ancestors of both nanoviruses and
humans but not all (e.g. Merkel cell circoviruses
polyomavirus is oncogenic) ○ Plant-infecting nanovirus had switched
● Intra-host molecular evolution to a herbivorous vertebrate first, and
 then recombined with a picorna-like
virus via retrotransposable element or a
retrovirus
■ Homologues of the ssDNA virus
Rep were described in plasmids
of eubacteria and algae
○ Close phylogenetic relatedness of
several circoviruses replicating in
various host species may be the sign of
cross-species transmissions
● The common presence of the highly conserved
Rep and the mechanism of the rolling circle
replication are the most obvious evidence for
common ancestry of ssDNA virus taxa and
ssDNA molecules