Orangutan Alu quiescence reveals possible source element: support for ancient backseat drivers

Here we report the identification of a nearly pristine insertion possessing all the known putative hallmarks of a retrotranspositionally competent Alu element. It is located in an intronic sequence of the DGKB gene on chromosome 7 and is highly conserved in Hominidae (the great apes), but absent from Hylobatidae (gibbon and siamang). We provide evidence for the evolution of a lineage-specific subfamily of this shared Alu insertion in orangutans and possibly the lineage leading to humans. In the orangutan genome, this insertion contains three orangutan-specific diagnostic mutations which are characteristic of the youngest polymorphic Alu subfamily, AluYe5b5_Pongo. In the Homininae lineage (human, chimpanzee and gorilla), this insertion has acquired three different mutations which are also found in a single human-specific Alu insertion.This seemingly stealth-like amplification, ongoing at a very low rate over millions of years of evolution, suggests that this shared insertion may represent an ancient backseat driver of Alu element expansion.The amplification of Alu elements has been ongoing in primate genomes for about 65 million years [1,2]. They typically mobilize via a 'copy and paste' mechanism through an RNA intermediate, a process termed target-primed reverse transcription (TPRT) [3]. Alu elements are non-autonomous and utilize the enzymatic machinery of autonomous LINE elements (L1) to mobilize [1,4,5]. Due to the staggered DNA cuts of the genome by the L1-derived endonuclease during TPRT, Alu insertions are flanked by short sequences of duplicated host DNA called target site duplications (TSDs), which can be used to identify the insertion event. Alu elements accumulate in an 'identical by descent' manner. This means that the ancestral state at any locus is the absence of the element and, conversely, that the presence of a shared element with matching TSDs at a given locus indicates a common ancestor. Thus, Alu elements are considered essentially homoplasy-free