Recent studies have shown that in addition to vertebrate retroviruses, virtually all types of eukaryotic viruses can be endogenized: that is, they can be integrated into the germline genome of their host and vertically inherited.
The endogenization of non-retroviral viruses is believed to result from accidental integration mediated by various mechanisms that are encoded either by the viral genome or by the host genome, such as DNA repair processes or resident retrotransposons.
Various endogenous viral elements (EVEs) have been dated, showing that the roots of several notorious viral families that are currently circulating in human and animal populations are much deeper than previously thought.
Long-term viral substitution rates estimated using the age of EVEs as a calibration point are several orders of magnitude slower than short-term viral substitution rates calculated through comparison of modern viral sequences.
The integration of EVEs in the host genome is an important source of structural variation, and EVEs can continue long after integration to provoke genomic rearrangements, some of which have been linked to cancer and other diseases.
Recent genome-wide studies have shown that thousands of mammalian endogenous retroviral sequences have been co-opted to control host gene expression, substantially contributing to regulatory innovation in mammals.
The domestication of EVE protein-coding sequences has led to the birth of new host genes, most of which are used to combat exogenous viruses or for the physiology and development of the placenta.
Recent studies have uncovered myriad viral sequences that are integrated or 'endogenized' in the genomes of various eukaryotes. Surprisingly, it appears that not just retroviruses but almost all types of viruses can become endogenous. We review how these genomic 'fossils' offer fresh insights into the origin, evolutionary dynamics and structural evolution of viruses, which are giving rise to the burgeoning field of palaeovirology. We also examine the multitude of ways through which endogenous viruses have influenced, for better or worse, the biology of their hosts. We argue that the conflict between hosts and viruses has led to the invention and diversification of molecular arsenals, which, in turn, promote the cellular co-option of endogenous viruses.
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We apologize to many colleagues who have produced primary research on the topic that could not be cited or discussed owing to space limitations. We thank the three anonymous reviewers for their constructive comments and useful suggestions. This work was supported by grant GM77582 from the US National Institutes of Health to C.F.
The authors declare no competing financial interests.
In the context of genetic information, horizontal transmission is the transfer of genetic material by means other than sex.
- Vertical transmission
Sexual transmission of genetic material from parent to offspring.
A mutation reaches fixation when it is present in all individuals of a given species.
- Transposable elements
Pieces of DNA (typically genomic elements) that are able to move from one locus to another, often duplicating themselves in the process.
- Reverse transcription
Synthesis of DNA from an RNA template.
Mobile intracellular genetic elements that replicate via reverse transcription of an RNA intermediate.
(Env). A glycoprotein encoded by many viruses that binds to host receptors located on the cell surface in order to promote viral entry.
- Non-homologous end joining
A DNA double-strand break repair pathway that does not make use of a template and is therefore intrinsically error-prone.
Describes a virus that can be transmitted between animals and humans or vice versa.
- Mutational saturation
A given site in a DNA sequence is saturated when the number of observed or inferred mutations is lower than the number of mutations that truly occurred at this site.
A period during which a virus replicates at a low rate without causing any symptoms to the host.
A saltational change is a profound and rapid change in the evolutionary dynamics of a viral lineage.
The joint study of the epidemiological and evolutionary dynamics of a virus.
The integrated form of a retrovirus.
Repeated infection of the germ cells of the individual carrying a provirus, with possible horizontal transmission to other individuals.
Full-length insertion present in some individuals but absent in others.
A class of antigens that cause nonspecific activation and uncontrolled proliferation of T cells, often resulting in a chronic inflammatory response.
A retroviral protein that is one of the structural proteins of the viral capsid.
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Feschotte, C., Gilbert, C. Endogenous viruses: insights into viral evolution and impact on host biology. Nat Rev Genet 13, 283–296 (2012). https://doi.org/10.1038/nrg3199
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