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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, low copy repeat (lcr)16a, 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 interchromosomal 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.

Phylogenetically new insertions of repetitive sequences may contribute to genome evolution by altering the function of preexisting proteins. One example is the SVA sequence, which forms the C-terminal coding exon of the human leptin receptor isoform 219.1. Here, we report that the SVA insertion into the LEPR locus has occurred after divergence of humans and chimpanzees. The SVA element was inserted into a Hal-1/LINE element present in all monkeys and apes tested. Structural features point toward an integration event that was mediated by the L1 protein machinery acting in trans. Thus, our findings add evidence to the hypothesis that retrotransposition events are a driving force in genomic evolution and that the presence or absence of specific retroelements are one distinguishing feature that separates humans from chimpanzees.

SVA (SINE-R-VNTR-Alu) elements constitute the youngest family of composite non-LTR retrotransposons in hominoid primates. The sequence of their assembly, however, remains unclear. Recently, a second family of VNTR-containing composites, LAVA (L1-Alu-VNTR-Alu), has been identified in gibbons. We now report the existence of two additional VNTR composite families, PVA (PTGR2-VNTR-Alu) and FVA (FRAM-VNTR-Alu), in the genome of Nomascus leucogenys. Like LAVA, they share the 5'-Alu-like region and VNTR with SVA, but differ at their 3'-ends. The 3'-end of PVA comprises part of the PTGR2 gene, whereas FVA is characterized by the presence of a partial FRAM element in its 3'-domain. Splicing could be identified as the mechanism of acquisition of the variant 3'-ends in all four families of VNTR composites. SVAs have been shown to be mobilized by the L1 protein machinery in trans. A critical role in this process has been ascribed to their 5'-hexameric repeat/ Alu-like region. The Alu-like region displays specific features in each of the VNTR composite families/subfamilies with characteristic deletions found in the evolutionary younger subfamilies. Using reciprocal exchanges between SVA_E and PVA/FVA elements, we demonstrate that the structure, not the presence of the (CCCTCT)n/ Alu-like region determines mobilization capacity. Combination of LAVA and SVA_E domains does not yield any active elements-suggesting the use of different combinations of host factors for the two major groups of VNTR composites. Finally, we demonstrate that the LAVA 3'-L1ME5 fragment attenuates mobilization capacity.