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      Non-Retroviral Fossils in Vertebrate Genomes

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          Abstract

          Although no physical fossils of viruses have been found, retroviruses are known to leave their molecular fossils in the genomes of their hosts, the so-called endogenous retroviral elements. These have provided us with important information about retroviruses in the past and their co-evolution with their hosts. On the other hand, because non-retroviral viruses were considered not to leave such fossils, even the existence of prehistoric non-retroviral viruses has been enigmatic. Recently, we discovered that elements derived from ancient bornaviruses, non-segmented, negative strand RNA viruses, are found in the genomes of several mammalian species, including humans. In addition, at approximately the same time, several endogenous elements of RNA viruses, DNA viruses and reverse-transcribing DNA viruses have been independently reported, which revealed that non-retroviral viruses have played significant roles in the evolution of their hosts and provided novel insights into virology and cell biology. Here we review non-retroviral virus-like elements in vertebrate genomes, non-retroviral integration and the knowledge obtained from these endogenous non-retroviral virus-like elements.

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          Most cited references35

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          Large-scale mapping of human protein–protein interactions by mass spectrometry

          Mapping protein–protein interactions is an invaluable tool for understanding protein function. Here, we report the first large-scale study of protein–protein interactions in human cells using a mass spectrometry-based approach. The study maps protein interactions for 338 bait proteins that were selected based on known or suspected disease and functional associations. Large-scale immunoprecipitation of Flag-tagged versions of these proteins followed by LC-ESI-MS/MS analysis resulted in the identification of 24 540 potential protein interactions. False positives and redundant hits were filtered out using empirical criteria and a calculated interaction confidence score, producing a data set of 6463 interactions between 2235 distinct proteins. This data set was further cross-validated using previously published and predicted human protein interactions. In-depth mining of the data set shows that it represents a valuable source of novel protein–protein interactions with relevance to human diseases. In addition, via our preliminary analysis, we report many novel protein interactions and pathway associations.
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            Human LINE retrotransposons generate processed pseudogenes.

            Long interspersed elements (LINEs) are endogenous mobile genetic elements that have dispersed and accumulated in the genomes of higher eukaryotes via germline transposition, with up to 100,000 copies in mammalian genomes. In humans, LINEs are the major source of insertional mutagenesis, being involved in both germinal and somatic mutant phenotypes. Here we show that the human LINE retrotransposons, which transpose through the reverse transcription of their own transcript, can also mobilize transcribed DNA not associated with a LINE sequence by a process involving the diversion of the LINE enzymatic machinery by the corresponding mRNA transcripts. This results in the 'retroposition' of the transcribed gene and the formation of new copies that disclose features characteristic of the widespread and naturally occurring processed pseudogenes: loss of intron and promoter, acquisition of a poly(A) 3' end and presence of target-site duplications of varying length. We further show-by introducing deletions within either coding sequence of the human LINE-that both ORFs are necessary for the formation of the processed pseudogenes, and that retroviral-like elements are not able to produce similar structures in the same assay. Our results strengthen the unique versatility of LINEs as genome modellers.
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              Effects of retroviruses on host genome function.

              For millions of years, retroviral infections have challenged vertebrates, occasionally leading to germline integration and inheritance as ERVs, genetic parasites whose remnants today constitute some 7% to 8% of the human genome. Although they have had significant evolutionary side effects, it is useful to view ERVs as fossil representatives of retroviruses extant at the time of their insertion into the germline and not as direct players in the evolutionary process itself. Expression of particular ERVs is associated with several positive physiological functions as well as certain diseases, although their roles in human disease as etiological agents, possible contributing factors, or disease markers-well demonstrated in animal models-remain to be established. Here we discuss ERV contributions to host genome structure and function, including their ability to mediate recombination, and physiological effects on the host transcriptome resulting from their integration, expression, and other events.
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                Author and article information

                Journal
                Viruses
                Viruses
                Molecular Diversity Preservation International (MDPI)
                1999-4915
                October 2011
                10 October 2011
                : 3
                : 10
                : 1836-1848
                Affiliations
                Laboratory of Human Tumor Viruses, Department of Viral Oncology, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; E-Mail: tomonaga@ 123456virus.kyoto-u.ac.jp
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: mhorie@ 123456virus.kyoto-u.ac.jp ; Tel.: +81-75-751-4034; Fax: +81-75-751-4000.
                Article
                viruses-03-01836
                10.3390/v3101836
                3205384
                22069518
                e1c71037-0f1b-4936-a971-15e8d3bca39d
                © 2011 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 3 August 2011
                : 22 September 2011
                : 27 September 2011
                Categories
                Review

                Microbiology & Virology
                endogenous non-retroviral virus-like elements,non-retroviral integration,viral fossil,exaptation,non-retroviral endogenization

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