Is there a role for endogenous retroviruses to mediate long-term adaptive phenotypic response upon environmental inputs?

Endogenous retroviruses (ERVs) are long terminal repeat-containing virus-like elements that have colonized approximately 10 per cent of the present day mammalian genomes. The intracisternal A particles (IAPs) are a class of ERVs that is currently highly active in the rodents. IAP elements can influence the transcription profile of nearby genes by providing functional promoter elements and modulating local epigenetic landscape through changes in DNA methylation and histone (H3K9) modifications. Despite the potential role for IAPs in gene regulation, the precise genomic locations where these elements are integrated are not well understood. To address this issue, we have identified more than 400 novel IAP insertion sites within/near annotated genes by searching the murine genome, which suggests that the impact of IAP elements on local and/or global gene regulation could be more profound than was previously expected. On the basis of our independent analyses and already published reports, here we argue that IAPs and ERV elements in general could have an evolutionary role for modulating phenotypic plasticity upon environmental inputs, and that this could be mediated through specific stages of embryonic development such as placentation during which the epigenetic constraints on IAP elements are partially relaxed.

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Tracking interspecies transmission and long-term evolution of an ancient retrovirus using the genomes of modern mammals

eLife ◽

10.7554/elife.12704 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 13

Author(s):

William E Diehl ◽

Nirali Patel ◽

Kate Halm ◽

Welkin E Johnson

Keyword(s):

Fossil Record ◽

Viral Infections ◽

Endogenous Retroviruses ◽

Interspecies Transmission ◽

Viral Spread ◽

Protein Functions ◽

History Of ◽

Mammalian Genomes ◽

Retroviral Infections

Mammalian genomes typically contain hundreds of thousands of endogenous retroviruses (ERVs), derived from ancient retroviral infections. Using this molecular 'fossil' record, we reconstructed the natural history of a specific retrovirus lineage (ERV-Fc) that disseminated widely between ~33 and ~15 million years ago, corresponding to the Oligocene and early Miocene epochs. Intercontinental viral spread, numerous instances of interspecies transmission and emergence in hosts representing at least 11 mammalian orders, and a significant role for recombination in diversification of this viral lineage were also revealed. By reconstructing the canonical retroviral genes, we identified patterns of adaptation consistent with selection to maintain essential viral protein functions. Our results demonstrate the unique potential of the ERV fossil record for studying the processes of viral spread and emergence as they play out across macro-evolutionary timescales, such that looking back in time may prove insightful for predicting the long-term consequences of newly emerging viral infections.

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Distribution, Diversity, and Evolution of Endogenous Retroviruses in Perissodactyl Genomes

Journal of Virology ◽

10.1128/jvi.00927-18 ◽

2018 ◽

Vol 92 (23) ◽

Author(s):

Henan Zhu ◽

Robert James Gifford ◽

Pablo Ramiro Murcia

Keyword(s):

Germ Line ◽

Mammalian Species ◽

Endogenous Retroviruses ◽

Functional Roles ◽

Physiological Processes ◽

Great Utility ◽

White Rhinoceros ◽

History Of ◽

Mammalian Genomes

ABSTRACTThe evolution of mammalian genomes has been shaped by interactions with endogenous retroviruses (ERVs). In this study, we investigated the distribution and diversity of ERVs in the mammalian orderPerissodactyla, with a view to understanding their impact on the evolution of modern equids (familyEquidae). We characterize the major ERV lineages in the horse genome in terms of their genomic distribution, ancestral genome organization, and time of activity. Our results show that subsequent to their ancestral divergence from rhinoceroses and tapirs, equids acquired four novel ERV lineages. We show that two of these ERV lineages proliferated extensively in the lineage leading to modern horses, and one contains loci that are actively transcribed in specific tissues. In addition, we show that the white rhinoceros has resisted germ line colonization by retroviruses for more than 54 million years—longer than any other extant mammalian species. The map of equine ERVs that we provide here will be of great utility to future studies aiming to investigate the potential functional roles of equine ERVs and their impact on equine evolution.IMPORTANCEERVs in the host genome are highly informative about the long-term interactions of retroviruses and hosts. They are also interesting because they have influenced the evolution of mammalian genomes in various ways. In this study, we derive a calibrated timeline describing the process through which ERV diversity has been generated in the equine germ line. We determined the distribution and diversity of perissodactyl ERV lineages and inferred their retrotranspositional activity during evolution, thereby gaining insight into the long-term coevolutionary history of retroviruses and mammals. Our study provides a platform for future investigations to identify equine ERV loci involved in physiological processes and/or pathological conditions.

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Retroviruses drive the rapid evolution of mammalianAPOBEC3genes

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1914183116 ◽

2019 ◽

Vol 117 (1) ◽

pp. 610-618 ◽

Cited By ~ 15

Author(s):

Jumpei Ito ◽

Robert J. Gifford ◽

Kei Sato

Keyword(s):

Gene Family ◽

Fossil Record ◽

Driving Force ◽

Mammalian Species ◽

Rapid Evolution ◽

Endogenous Retroviruses ◽

Mammalian Evolution ◽

History Of ◽

Mammalian Genomes

APOBEC3(A3) genes are members of theAID/APOBECgene family that are found exclusively in mammals.A3genes encode antiviral proteins that restrict the replication of retroviruses by inducing G-to-A mutations in their genomes and have undergone extensive amplification and diversification during mammalian evolution. Endogenous retroviruses (ERVs) are sequences derived from ancient retroviruses that are widespread mammalian genomes. In this study we characterize theA3repertoire and use the ERV fossil record to explore the long-term history of coevolutionary interaction between A3s and retroviruses. We examine the genomes of 160 mammalian species and identify 1,420AID/APOBEC-related genes, including representatives of previously uncharacterized lineages. We show thatA3genes have been amplified in mammals and that amplification is positively correlated with the extent of germline colonization by ERVs. Moreover, we demonstrate that the signatures of A3-mediated mutation can be detected in ERVs found throughout mammalian genomes and show that in mammalian species with expandedA3repertoires, ERVs are significantly enriched for G-to-A mutations. Finally, we show thatA3amplification occurred concurrently with prominent ERV invasions in primates. Our findings establish that conflict with retroviruses is a major driving force for the rapid evolution of mammalianA3genes.

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An ancient retroviral RNA element hidden in mammalian genomes and its involvement in co-opted retroviral gene regulation

Retrovirology ◽

10.1186/s12977-021-00580-2 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Koichi Kitao ◽

So Nakagawa ◽

Takayuki Miyazawa

Keyword(s):

Gene Expression ◽

Molecular Mechanisms ◽

Endogenous Retroviruses ◽

Sequence Motifs ◽

Specific Sequence ◽

Rna Regulation ◽

Mammalian Genomes ◽

Rna Elements ◽

Viral Sequences

Abstract Background Retroviruses utilize multiple unique RNA elements to control RNA processing and translation. However, it is unclear what functional RNA elements are present in endogenous retroviruses (ERVs). Gene co-option from ERVs sometimes entails the conservation of viral cis-elements required for gene expression, which might reveal the RNA regulation in ERVs. Results Here, we characterized an RNA element found in ERVs consisting of three specific sequence motifs, called SPRE. The SPRE-like elements were found in different ERV families but not in any exogenous viral sequences examined. We observed more than a thousand of copies of the SPRE-like elements in several mammalian genomes; in human and marmoset genomes, they overlapped with lineage-specific ERVs. SPRE was originally found in human syncytin-1 and syncytin-2. Indeed, several mammalian syncytin genes: mac-syncytin-3 of macaque, syncytin-Ten1 of tenrec, and syncytin-Car1 of Carnivora, contained the SPRE-like elements. A reporter assay revealed that the enhancement of gene expression by SPRE depended on the reporter genes. Mutation of SPRE impaired the wild-type syncytin-2 expression while the same mutation did not affect codon-optimized syncytin-2, suggesting that SPRE activity depends on the coding sequence. Conclusions These results indicate multiple independent invasions of various mammalian genomes by retroviruses harboring SPRE-like elements. Functional SPRE-like elements are found in several syncytin genes derived from these retroviruses. This element may facilitate the expression of viral genes, which were suppressed due to inefficient codon frequency or repressive elements within the coding sequences. These findings provide new insights into the long-term evolution of RNA elements and molecular mechanisms of gene expression in retroviruses.

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The impact of endogenous retroviruses on nuclear organization and gene expression

10.1101/295329 ◽

2018 ◽

Author(s):

Ramya Raviram ◽

Pedro P Rocha ◽

Vincent M Luo ◽

Emily Swanzey ◽

Emily R Miraldi ◽

...

Keyword(s):

Gene Regulation ◽

Transposable Elements ◽

Target Genes ◽

Endogenous Retrovirus ◽

Endogenous Retroviruses ◽

Chromosome Conformation ◽

Repetitive Nature ◽

Topologically Associated Domains ◽

The Individual ◽

The Impact

AbstractBackgroundThe organization of chromatin in the nucleus plays an essential role in gene regulation. When considering the mammalian genome it is important to take into account that about half of the DNA is comprised of transposable elements. Given their repetitive nature, reads associated with these elements are generally discarded or randomly distributed among elements of the same type in genome-wide analyses. Thus, it is challenging to identify the activities and properties of individual transposons. As a result, we only have a partial understanding of how transposons contribute to chromatin folding and how they impact gene regulation.ResultsUsing adapted PCR and Capture-based chromosome conformation capture (3C) approaches, collectively called 4Tran, we take advantage of the repetitive nature of transposons to capture interactions from multiple copies of endogenous retrovirus (ERVs) in the human and mouse genomes. With 4Tran-PCR, reads are selectively mapped to unique regions in the genome. This enables the identification of TE interaction profiles for individual ERV families and integration events specific to particular genomes. With this approach we demonstrate that transposons engage in long-range intra-chromosomal interactions guided by the separation of chromosomes into A and B compartments as well as topologically associated domains (TADs). In contrast to 4Tran-PCR, Capture-4Tran can uniquely identify both ends of an interaction that involve retroviral repeat sequences, providing a powerful tool for uncovering the individual TE insertions that interact with, and potentially regulate target genes.Conclusions4Tran provides new insight into the manner in which transposons contribute to chromosome architecture and identifies target genes that transposable elements can potentially control.

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Suppressed, but Not Forgotten

Swiss Journal of Psychology ◽

10.1024/1421-0185/a000033 ◽

2011 ◽

Vol 70 (1) ◽

pp. 5-11 ◽

Cited By ~ 8

Author(s):

Beat Meier ◽

Anja König ◽

Samuel Parak ◽

Katharina Henke

Keyword(s):

Memory Trace ◽

Thought Suppression ◽

Test Phase ◽

Indirect Test ◽

Final Test ◽

Test Experiment ◽

And Control ◽

Cue Words ◽

The Impact

This study investigates the impact of thought suppression over a 1-week interval. In two experiments with 80 university students each, we used the think/no-think paradigm in which participants initially learn a list of word pairs (cue-target associations). Then they were presented with some of the cue words again and should either respond with the target word or avoid thinking about it. In the final test phase, their memory for the initially learned cue-target pairs was tested. In Experiment 1, type of memory test was manipulated (i.e., direct vs. indirect). In Experiment 2, type of no-think instructions was manipulated (i.e., suppress vs. substitute). Overall, our results showed poorer memory for no-think and control items compared to think items across all experiments and conditions. Critically, however, more no-think than control items were remembered after the 1-week interval in the direct, but not in the indirect test (Experiment 1) and with thought suppression, but not thought substitution instructions (Experiment 2). We suggest that during thought suppression a brief reactivation of the learned association may lead to reconsolidation of the memory trace and hence to better retrieval of suppressed than control items in the long term.

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