An endogenous viral element (EVE) is a
DNA
Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
sequence derived from a
virus
A virus is a submicroscopic infectious agent that replicates only inside the living Cell (biology), cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Viruses are ...
, and present within the
germline of a
non-viral organism. EVEs may be entire viral genomes (
proviruses), or fragments of viral genomes. They arise when a viral DNA sequence becomes integrated into the
genome
A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...
of a
germ cell
A germ cell is any cell that gives rise to the gametes of an organism that reproduces sexually. In many animals, the germ cells originate in the primitive streak and migrate via the gut of an embryo to the developing gonads. There, they unde ...
that goes on to produce a viable organism. The newly established EVE can be
inherited from one generation to the next as an
allele
An allele is a variant of the sequence of nucleotides at a particular location, or Locus (genetics), locus, on a DNA molecule.
Alleles can differ at a single position through Single-nucleotide polymorphism, single nucleotide polymorphisms (SNP), ...
in the host species, and may even reach
fixation.
Endogenous retroviruses and other EVEs that occur as proviruses can potentially remain capable of producing
infectious virus in their endogenous state. Replication of such 'active' endogenous viruses can lead to the proliferation of viral insertions in the germline. For most non-retroviral viruses, germline integration appears to be a rare, anomalous event, and the resulting EVEs are often only fragments of the parent virus genome. Such fragments are usually not capable of producing infectious virus, but may express
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
or
RNA
Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...
and even
cell surface receptors
Cell surface receptors (membrane receptors, transmembrane receptors) are receptor (biochemistry), receptors that are embedded in the cell membrane, plasma membrane of cell (biology), cells. They act in cell signaling by receiving (binding to) ex ...
.
Diversity and distribution
EVEs have been identified in
animal
Animals are multicellular, eukaryotic organisms in the Biology, biological Kingdom (biology), kingdom Animalia (). With few exceptions, animals heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, ...
s,
plant
Plants are the eukaryotes that form the Kingdom (biology), kingdom Plantae; they are predominantly Photosynthesis, photosynthetic. This means that they obtain their energy from sunlight, using chloroplasts derived from endosymbiosis with c ...
s and
fungi
A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and mold (fungus), molds, as well as the more familiar mushrooms. These organisms are classified as one ...
.
[
][
] In
vertebrate
Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain.
The vertebrates make up the subphylum Vertebra ...
s EVEs derived from
retroviruses (
endogenous retroviruses) are relatively common. Because retroviruses integrate into the
nuclear genome of the
host cell as an inherent part of their
replication cycle, they are predisposed to enter the host germline. In addition, EVEs related to
parvoviruses,
filoviruses,
bornaviruses and
circoviruses have been identified in vertebrate genomes. In plant genomes, EVEs derived from
pararetroviruses are relatively common. EVEs derived from other, non-retrotranscribing virus families, such as ''
Geminiviridae'', have also been identified in plants. Moreover, EVEs related to
giant viruses (aka GEVEs) of
phylum
In biology, a phylum (; : phyla) is a level of classification, or taxonomic rank, that is below Kingdom (biology), kingdom and above Class (biology), class. Traditionally, in botany the term division (taxonomy), division has been used instead ...
''
Nucleocytoviricota'' (NCLDV) similar to ''
Aureococcus anophagefferens virus'' (AaV) have been found in 2019/2020.
Identification
EVEs are traditionally identified by similarity to known viruses. In 2021, it has been demonstrated that the
k-mer composition of endogenous RNA virus resemble that of their exogenous counterparts. As a result, it is now possible to identify novel groups of endogenous RNA viruses whose exogenous relatives have become extinct.
Use in paleovirology
EVEs are a rare source of retrospective information about ancient viruses. Many are derived from germline integration events that occurred millions of years ago, and can be viewed as viral
fossil
A fossil (from Classical Latin , ) is any preserved remains, impression, or trace of any once-living thing from a past geological age. Examples include bones, shells, exoskeletons, stone imprints of animals or microbes, objects preserve ...
s. Such ancient EVEs are an important component of
paleovirological studies that address the long-term
evolution
Evolution is the change in the heritable Phenotypic trait, characteristics of biological populations over successive generations. It occurs when evolutionary processes such as natural selection and genetic drift act on genetic variation, re ...
of viruses.
Identification of
orthologous EVE insertions enables the calibration of long-term evolutionary timelines for viruses, based on the estimated time since
divergence
In vector calculus, divergence is a vector operator that operates on a vector field, producing a scalar field giving the rate that the vector field alters the volume in an infinitesimal neighborhood of each point. (In 2D this "volume" refers to ...
of the ortholog-containing host species groups. This approach has provided minimum ages ranging from 30 to 93 million years for the ''
Parvoviridae
Parvoviruses are a family of animal viruses that constitute the family ''Parvoviridae''. They have linear, single-stranded DNA (ssDNA) genomes that typically contain two genes encoding for a replication initiator protein, called NS1, and the pr ...
'', ''
Filoviridae'',
''Bornaviridae'' and ''
Circoviridae
''Circoviridae'' is a family of DNA viruses. Birds and mammals serve as natural hosts. The family has two genera. Diseases associated with this family include: PCV-2: postweaning multisystemic wasting syndrome; CAV: chicken infectious anemia.
...
'' families of viruses,
>100 million years in the ''
Flaviviridae
''Flaviviridae'' is a family of Viral envelope, enveloped positive-strand RNA viruses which mainly infect mammals and birds. They are primarily spread through arthropod vector (epidemiology), vectors (mainly ticks and mosquitoes). The family gets ...
'',
[ ] and 12 million years for the
Lentivirus genus of the
''Retroviridae'' family. EVEs also facilitate the use of
molecular clock-based approaches to obtain calibrations of viral evolution in
deep time.
[
]
Co-option and exaptation by host species
EVEs can sometimes provide a
selective advantage to the individuals in which they are inserted. For example, some protect against infection with related viruses.
In some mammal groups, including
higher primates, retroviral
envelope proteins have been
exapted to produce a protein that is expressed in the
placenta
The placenta (: placentas or placentae) is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas, and waste exchange between ...
l
syncytiotrophoblast, and is involved in fusion of the
cytotrophoblast cells to form the
syncytial layer of the placenta. In humans this protein is called
syncytin, and is encoded by an
endogenous retrovirus called (
ERVWE1) on
chromosome seven. Remarkably, the capture of syncytin or syncytin-like genes has occurred independently, from different groups of endogenous retroviruses, in diverse mammalian
lineages. Distinct, syncytin-like genes have been identified in
primates
Primates is an order of mammals, which is further divided into the strepsirrhines, which include lemurs, galagos, and lorisids; and the haplorhines, which include tarsiers and simians ( monkeys and apes). Primates arose 74–63 ...
,
rodent
Rodents (from Latin , 'to gnaw') are mammals of the Order (biology), order Rodentia ( ), which are characterized by a single pair of continuously growing incisors in each of the upper and Mandible, lower jaws. About 40% of all mammal specie ...
s,
lagomorphs,
carnivore
A carnivore , or meat-eater (Latin, ''caro'', genitive ''carnis'', meaning meat or "flesh" and ''vorare'' meaning "to devour"), is an animal or plant
Plants are the eukaryotes that form the Kingdom (biology), kingdom Plantae; they ar ...
s, and
ungulates, with integration dates ranging from 10 to 85 million years ago.
[
]
See also
*
Ancient DNA
*
Avian sarcoma leukosis virus (ASLV)
*
Endogenous retrovirus
*
ERV3
*
HERV-FRD
*
Jaagsiekte sheep retrovirus (JSRV)
*
Koala retrovirus
Koala retrovirus (KoRV) is a retrovirus that is present in many populations of koalas. It has been implicated as the agent of koala immune deficiency syndrome (KIDS), an HIV/AIDS, AIDS-like immunodeficiency that leaves infected koalas more susce ...
(KoRV)
*
Mouse mammary tumor virus (MMTV)
*
Murine leukemia virus (MLV), and
xenotropic murine leukemia virus-related virus (XMRV)
*
Paleovirology
*
Polydnavirus
*
Viral eukaryogenesis
References
{{Organisms et al.
Virology