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LINE-1 ORF1p does not determine substrate preference for human/orangutan SVA and gibbon LAVA
1Primate Genetics Laboratory, German Primate Center, Leibniz Institute for Primate Research, Göttingen, Germany.
Mobile DNA
|July 18, 2020
Summary
Human SVA retrotransposons are highly active and preferred substrates for LINE-1 machinery. Orangutan L1 ORF1p shows reduced mobilization of SVA/LAVA, potentially explaining differing insertion rates across lineages.
Area of Science:
- Genetics
- Molecular Biology
- Evolutionary Biology
Background:
- Non-autonomous VNTR composite retrotransposons SVA and LAVA are primate-specific.
- SVA and LAVA are mobilized by LINE-1 (L1) machinery, but human SVA retrotransposition efficiency in vitro is lower than expected.
- VNTR composites in hominoids exhibit distinct 5' Alu-like domains and VNTRs, with lineage-specific active L1 subfamilies.
Purpose of the Study:
- To identify and functionally characterize a highly active human SVA element.
- To investigate the role of VNTR and 5' hexameric repeats in SVA mobilization efficiency.
- To assess the substrate preference of L1 ORF1 proteins from different hominoid lineages for SVA/LAVA retrotransposition.
Main Methods:
- Utilized an improved retrotransposition reporter cassette (mneoM) to minimize splicing.
- Performed SVA deletion analysis to identify key mobilization elements.
- Conducted cross-species comparisons of SVA/LAVA retrotransposition using modified reporter cassettes.
Main Results:
- Identified a highly active human SVA element with key mobilization elements in the VNTR and 5' hexameric repeats.
- Demonstrated that L1 ORF1 proteins from gibbon, orangutan, and human do not show substrate preference for SVA/LAVA.
- Showed that orangutan L1 ORF1p has limited SVA/LAVA mobilization in trans, despite full L1 mobilization in cis.
Conclusions:
- Confirms SVA as a highly active human retrotransposon and a preferred substrate for L1-encoded machinery.
- Suggests coevolution of L1 ORF1p and VNTR composites is unlikely in humans.
- Proposes that reduced orangutan L1 ORF1p mobilization capacity in trans may explain differential SVA insertion rates between orangutan and hominine lineages.
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