SVA (SINE/VNTR/Alu) Element Expansion

SVA elements are a family of non-autonomous retroelements within the primate lineage. They originally were named “SINE-R” elements, with the “R” indicating a sequence of retroviral origin. However, in 1994, Shen et al. identified a composite retroelement during studies of the retinitis pigmentosa (Rp) gene, and renamed this retroelement “SVA” after its three main components, SINE-R, VNTR and Alu. Over half of the SVA elements in primate genomes are full-length and they exhibit hallmarks of retroelements, indicating that they likely are mobilized in trans by target primed reverse transcription using the endonuclease and reverse transcriptase activities encoded by L1 elements. In general, SVA elements flanked by TSDs (target site duplications), terminate in a poly (A) tails, and can become truncated and/or inverted during their integration into the genome. Individual SVA elements also may vary in size as a result of polymorphisms in the VNTR.

SVA elements are a relative newcomer to primate genomes. They arose as a family of repeats after the divergence of hominids from old world monkeys and their distribution of SVA elements is restricted to hominids. SVA elements have a variable copy number in the hominid lineage with about 2700 copies in the humans. Similar to Alu and L1 elements, SVA elements also appear to have followed a model of relatively limited proliferation, which has given rise to a hierarchical subfamily structure of elements with shared diagnostic sequence characters.

SVA elements have continued to amplify in primate genomes and new SVA insertions of have been implicated as the causative agents for several human diseases. Like L1s, SVA elements can also transduce 5’ and 3’ flanking genomic DNA sequences to new genomic locations. This process can lead to exon shuffling and, in one instance, the creation of a new gene family in the primate lineage. Thus, like other retroelements, SVA insertions can have both negative and potentially positive effects on the genome.