Structural and transduction patterns of human-specific polymorphic SVA insertions

Kirby, Ashley E.; Loftus, Mark; Golba, Emily C.; Konkel, Miriam K.

Structural and transduction patterns of human-specific polymorphic SVA insertions

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Item Type:	Article
Title:	Structural and transduction patterns of human-specific polymorphic SVA insertions
Creators Name:	Kirby, Ashley E., Loftus, Mark, Golba, Emily C. and Konkel, Miriam K.
Abstract:	BACKGROUND: SINE variable number tandem repeat Alu elements (SVAs) are a unique group of hominid-specific composite retrotransposons with highly variable internal structure. They represent the youngest TE family in humans and contribute to genetic diversity, evolution, and disease. Recent findings indicate that SVA mobilization rates may exceed previous estimates, and many SVAs exhibit insertion polymorphism. SVAs facilitate transduction (TD) events when transcription initiates upstream of a source element, or when their internal termination signal is bypassed, mobilizing adjacent 5’ and/or 3’ sequence. To investigate features of non-reference SVA elements currently polymorphic in the human genome, we analyzed a structural variant callset built upon 35 diverse human genomes generated by the Human Genome Structural Variation Consortium. RESULTS: In our curated dataset of 543 polymorphic, non-reference SVAs, we identify insertions representing the three youngest subfamilies: D (7%), E (38%), and F (55%). Of the latter, we determine that at least 47% are actually SVA_F1, a more recently discovered human-specific subfamily, indicating that F1 is a major contributor to SVA expansion in the human population. We further uncover that 40% of non-reference SVAs carry a TD on their 5’ and/or 3’ ends. Of these, the majority (69%) harbor sequence originating in a gene, including 14 exonic events and the mobilization of a processed pseudogene, supporting the role of SVA in exon shuffling. In addition, we identified a so-called “orphan” TD, defined by the absence of SVA sequence at the insertion site. Leveraging TD origin coordinates, we identify 55 active source elements, including nine non-reference and 46 across GRCh38 and T2T-CHM13, giving rise to 84% of TD-carrying SVAs. CONCLUSIONS: Our analyses indicate that SVA_F1 is more active than previously described and is a main driver of SVA expansion. We find two-fold more TD events compared to previous estimates, with an unexpected bias toward 3’ events. Finally, we postulate that the discrepant SVA mobilization rate may be attributed to inter-individual variation in the presence/absence of source elements, a recent uptick in mobilization supported by overall low allele frequencies, and/or negative selection against deleterious insertions.
Keywords:	Retrotransposon, Transposable Element, Mobile Element Insertion, SVA, Subfamily, Polymorphism, Transduction, Source Element, Genetic Variation, Structural Variation, Human Specific
Source:	Mobile DNA
ISSN:	1759-8753
Publisher:	BioMed Central
Volume:	16
Number:	1
Page Range:	42
Date:	6 November 2025
Additional Information:	Ashley D. Sanders is a member of the Human Genome Structural Variation Consortium.
Official Publication:	https://doi.org/10.1186/s13100-025-00373-w
PubMed:	View item in PubMed
Related to:	URL URL Type https:/www.internationalgenome.org/data-portal/data-collection/hgsvc2 External Dataset

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