Co-option of the gibbon-specific LAVA retrotransposon in DNA repair pathways [preprint]
Okhovat, Mariam ; Nevonen, Kimberly A. ; Davis, Brett ; Michener, Pryce ; Ward, Samantha ; Milhaven, Mark ; Harshman, Lana ; Sohota, Ajuni ; O’Neill, Rachel J. ; Ahituv, Nadav ... show 2 more
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gibbons
genomes
LAVA retrotransposon
DNA
Transposable elements
Amino Acids, Peptides, and Proteins
Biochemical Phenomena, Metabolism, and Nutrition
Biochemistry, Biophysics, and Structural Biology
Ecology and Evolutionary Biology
Genetic Phenomena
Genetics and Genomics
Nucleic Acids, Nucleotides, and Nucleosides
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Abstract
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 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.
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bioRxiv 765230; doi: https://doi.org/10.1101/765230. Link to preprint on bioRxiv service.
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Now published in Proceedings of the National Academy of Sciences doi: 10.1073/pnas.2006038117