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dc.contributor.authorOkhovat, Mariam
dc.contributor.authorNevonen, Kimberly A.
dc.contributor.authorDavis, Brett
dc.contributor.authorMichener, Pryce S.
dc.contributor.authorWard, Samantha
dc.contributor.authorMilhaven, Mark
dc.contributor.authorHarshman, Lana
dc.contributor.authorSohota, Ajuni
dc.contributor.authorO’Neill, Rachel J.
dc.contributor.authorAhituv, Nadav
dc.contributor.authorVeeramah, Krishna R.
dc.contributor.authorCarbone, Lucia
dc.date2022-08-11T08:08:24.000
dc.date.accessioned2022-08-23T15:53:41Z
dc.date.available2022-08-23T15:53:41Z
dc.date.issued2019-09-11
dc.date.submitted2019-09-19
dc.identifier.citation<p>bioRxiv 765230; doi: https://doi.org/10.1101/765230. <a href="https://doi.org/10.1101/765230" target="_blank">Link to preprint on bioRxiv service.</a></p>
dc.identifier.doi10.1101/765230
dc.identifier.urihttp://hdl.handle.net/20.500.14038/29401
dc.description.abstractTransposable elements (TEs) can shape gene regulation networks by being co-opted as enhancers. However, the contribution of lineage-specific TE insertions to recent adaptations remains poorly understood. Gibbons present a suitable model to study these contributions, as they have evolved many distinct traits, including heavily rearranged genomes and a novel TE called LAVA. The LAVA retrotransposon is still active in the gibbon genome and is thought to have contributed to evolution of gibbon-specific traits. In this study, we characterized fixed and polymorphic LAVA insertions across multiple gibbon genomes and found that 10% of all LAVA elements overlap chromatin states associated with enhancer function. Moreover, LAVA was enriched in multiple transcription factor motifs, was bound by the important lymphoid transcription factor PU.1, and was associated with higher levels of gene expression in cis. Interestingly, despite the highly similar genomic distribution and epigenetic characteristics of fixed and polymorphic LAVA, only fixed LAVA insertions showed strong signatures of positive selection, and were enriched near genes implicated in DNA repair. Altogether, our population genetics, epigenetics, and evolutionary analyses indicate that several LAVA insertions have been co-opted in the gibbon genome as cis-regulatory elements. Specifically, a subset of the fixed LAVA insertions appear to have been co-opted to enhance regulation of DNA repair genes, likely as an adaptive mechanism to improve genome integrity in response to the genomic rearrangements occurring in the gibbon lineage.
dc.language.isoen_US
dc.relationNow published in Proceedings of the National Academy of Sciences doi: 10.1073/pnas.2006038117
dc.rightsThe copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectEvolutionary Biology
dc.subjectgibbons
dc.subjectgenomes
dc.subjectLAVA retrotransposon
dc.subjectDNA
dc.subjectTransposable elements
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectBiochemical Phenomena, Metabolism, and Nutrition
dc.subjectBiochemistry, Biophysics, and Structural Biology
dc.subjectEcology and Evolutionary Biology
dc.subjectGenetic Phenomena
dc.subjectGenetics and Genomics
dc.subjectNucleic Acids, Nucleotides, and Nucleosides
dc.titleCo-option of the gibbon-specific LAVA retrotransposon in DNA repair pathways [preprint]
dc.typePreprint
dc.source.journaltitlebioRxiv
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2639&amp;context=faculty_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/1630
dc.identifier.contextkey15376223
refterms.dateFOA2022-08-23T15:53:41Z
html.description.abstract<p>Transposable elements (TEs) can shape gene regulation networks by being co-opted as enhancers. However, the contribution of lineage-specific TE insertions to recent adaptations remains poorly understood. Gibbons present a suitable model to study these contributions, as they have evolved many distinct traits, including heavily rearranged genomes and a novel TE called <em>LAVA</em>. The LAVA retrotransposon is still active in the gibbon genome and is thought to have contributed to evolution of gibbon-specific traits. In this study, we characterized fixed and polymorphic LAVA insertions across multiple gibbon genomes and found that 10% of all LAVA elements overlap chromatin states associated with enhancer function. Moreover, LAVA was enriched in multiple transcription factor motifs, was bound by the important lymphoid transcription factor PU.1, and was associated with higher levels of gene expression in <em>cis</em>. Interestingly, despite the highly similar genomic distribution and epigenetic characteristics of fixed and polymorphic LAVA, only fixed LAVA insertions showed strong signatures of positive selection, and were enriched near genes implicated in DNA repair. Altogether, our population genetics, epigenetics, and evolutionary analyses indicate that several LAVA insertions have been co-opted in the gibbon genome as <em>cis</em>-regulatory elements. Specifically, a subset of the fixed LAVA insertions appear to have been co-opted to enhance regulation of DNA repair genes, likely as an adaptive mechanism to improve genome integrity in response to the genomic rearrangements occurring in the gibbon lineage.</p>
dc.identifier.submissionpathfaculty_pubs/1630
dc.contributor.departmentGraduate School of Biomedical Sciences


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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.
Except where otherwise noted, this item's license is described as The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.