SVA Retrotransposons and a Low Copy Repeat in Humans and Great Apes: A Mobile Connection

Abstract

Segmental duplications (SDs) constitute a considerable fraction of primate genomes. They contribute to genetic variation and provide raw material for evolution. Groups of SDs are characterized by the presence of shared core duplicons. One of these core duplicons, lcr16a, has been shown to be particularly active in the propagation of interspersed SDs in primates. The underlying mechanisms are, however, only partially understood. Alu short interspersed elements (SINEs) are frequently found at breakpoints and have been implicated in the expansion of SDs. Detailed analysis of lcr16a-containing SDs shows that the hominid-specific SVA (SINE-R-VNTR-Alu) retrotransposon is an integral component of the core duplicon in Asian and African great apes. In orang-utan it provides breakpoints and contributes to both inter- and intrachromosomal lcr16a mobility by inter-element recombination. Furthermore, the data suggest that in hominines (human, chimpanzee, gorilla) SVA recombination-mediated integration of a circular intermediate is the founding event of a lineage-specific lcr16a expansion. One of the hominine lcr16a copies displays large flanking direct repeats, a structural feature shared by other SDs in the human genome. Taken together, the results obtained extend the range of SVAs’ contribution to genome evolution from RNA-mediated transduction to DNA-based recombination. In addition, they provide further support for a role of circular intermediates in SD mobilization.

Genomic structural variation: A complex but important driver of human evolution

“…However, association with Alu elements significantly decreases for younger SDs and CNVs, suggesting newly‐emerging molecular mechanisms underlying structural variation formation, with newer events driven by other repeat classes or different molecular mechanisms such as non‐homologous end‐joining (NHEJ) (Balachandran et al, 2022; Kim et al, 2008). In the case of the LCR16a core duplicon, which contains the rapidly‐evolving primate‐specific gene family Morpheus ( NPIP ), their interchromosomal and intrachromosomal expansions have been linked to the hominid‐specific retrotransposon SINE‐R‐VNTR‐ Alu (SVA) (Damert, 2022).…”

Structural Variation Evolution at the 15q11-q13 Disease-Associated Locus

“…These were followed by LTRs (Table S5). It is well documented that LINEs can play a structural role in promoting gene duplication [48], and Alu-mediated mechanisms have been suggested to enhance the generation of CNVs and SDs [49].…”