Figure 3.

The origin of SVA. A model outlining events that may have taken place to generate each junction and domain within a modern SVA is displayed. The events and junction formation are ordered from 5’ to 3’ for clarity (see text for further description). However whether the SVA domains were acquired by SVA2 independently or simultaneously is unknown. (A) An mRNA (red line) consisting of a CCCTCT hexameric repeat transcribed (black bent arrows) from a genomic location (black boxes) spliced into a downstream antisense Alu at the known 3’SS position 279 relative to Alu_Rep creating the junction between the CCCTCT hexamer and the first Alu (B). Most likely in the same mRNA (B, red line), the first Alu was spliced out at position 23, a known Alu 5’SS, followed by subsequent splicing into a sequence of unknown origin, referred to as SVA-U. SVA-U presumably spliced into the second Alu presumably at a known Alu 3’SS between positions 273–281. Here we display Alu position 279 as the 3’SS utilized in the incorporation of the second Alu. The CCCTCT hexamer along with the Alu-like domain junctions are displayed (C) prior to deletions in the second Alu. The 3’end of the second Alu is a 5’SS, therefore the second Alu and VNTR junction was likely created by alternative splicing into a genomic SVA2 (C). During its evolution, two deletions in the second Alu from 1) the 3’SS to nt 262 and 2) nts 208-57 were generated (E). The SINE-R domain may have been acquired by potentially one of two RNA based mechanisms: 1) ORF2 reverse transcriptase template switching (F) or 2) alternative splicing (G) at an unidentifiable 3’SS in the env sequence of a HERV-K resulting in an mRNA resembling a modern SVA (H). Subsequently, the mRNA was retrotransposed resulting in present-day SVA (I). It is unclear whether the 367 nt deletion (H; black triangle) present within the LTR occurred before or after SVA assembled.