Retrocopies

Retrocopies are gene duplicates generated by the reverse transcription of an RNA transcript and its reintegration into the genome. Also known as processed pseudogenes when nonfunctional, they can also become functional retrogenes if they acquire regulatory elements that drive expression and a viable open reading frame.

Most retrocopies originate from expressed genes and, because they are derived from spliced mRNA, they typically lack introns. They often lack promoter sequences and may include remnants of a poly-A tail. Insertion is usually mediated by LINE-1 reverse transcriptase and endonuclease, a process called target-primed reverse transcription, which creates short target-site duplications at the insertion site. Retrocopies are identified by sequence similarity to a parent gene but absence of introns, and by features such as poly-A remnants and TSDs.

Functional status varies. The majority are nonfunctional due to disabling mutations and are catalogued as processed pseudogenes. A subset, called retrocopies or retrogenes, can be transcribed and translated if they acquire regulatory elements; this can lead to novel gene functions or tissue-specific expression. Retrocopies can also influence the regulation of neighboring genes or participate in gene networks through noncoding transcripts.

Evolutionary significance: Retroposition provides a mechanism for rapid gene duplication and genetic innovation. The abundance of retropseudogenes in many genomes, including humans, reflects historical retrotransposon activity; comparative genomics uses retrocopies to study phylogeny and genome evolution.