The Genomic Impact of Gene Retrocopies: What Have We Learned from Comparative Genomics, Population Genomics, and Transcriptomic Analyses?

Abstract

Gene duplication is a major driver of organismal evolution. Gene retroposition is a mechanism of gene duplication whereby a gene’s transcript is used as a template to generate retroposed gene copies, or retrocopies. Intriguingly, the formation of retrocopies depends upon the enzymatic machinery encoded by retrotransposable elements, genomic parasites occurring in the majority of eukaryotes. Most retrocopies are depleted of the regulatory regions found upstream of their parental genes; therefore, they were initially considered transcriptionally incompetent gene copies, or retropseudogenes. However, examples of functional retrocopies, or retrogenes, have accumulated since the 1980s. Here, we review what we have learned about retrocopies in animals, plants and other eukaryotic organisms, with a particular emphasis on comparative and population genomic analyses complemented with transcriptomic datasets. In addition, these data have provided information about the dynamics of the different “life cycle” stages of retrocopies (i.e., polymorphic retrocopy number variants, fixed retropseudogenes and retrogenes) and have provided key insights into the retroduplication mechanisms, the patterns and evolutionary forces at work during the fixation process and the biological function of retrogenes. Functional genomic and transcriptomic data have also revealed that many retropseudogenes are transcriptionally active and a biological role has been experimentally determined for many. Finally, we have learned that not only non-long terminal repeat retroelements but also long terminal repeat retroelements play a role in the emergence of retrocopies across eukaryotes. This body of work has shown that mRNA-mediated duplication represents a widespread phenomenon that produces an array of new genes that contribute to organismal diversity and adaptation.

Pinaceae show elevated rates of gene turnover that are robust to incomplete gene annotation

“…Mutational mechanisms that produce gene duplication and gene loss events are associated with recombinationdependent processes (Zhang, 2003), gene retrotransposition (Casola and Betran, 2017), fork stalling and template switching (Zhang et al, 2009), and changes in the chromosome number including WGD (Conant et al, 2014;Van de Peer et al, 2017). These mechanisms largely differ from those generating single-base pair mutations, although gene loss can also be generated through single nucleotide loss-of-function mutations.…”

Pinaceae show elevated rates of gene duplication and gene loss that are robust to incomplete gene annotation

“…Mutational mechanisms that produce gene duplication and gene loss events are associated with recombination-dependent processes (Zhang 2003), gene retrotransposition (Casola and Betran 2017), fork stalling and template switching (Zhang, et al 2009) and changes in the chromosome number including whole-genome duplications (Conant, et al 2014;Van de Peer, et al 2017). These mechanisms largely differ from those generating single base pair mutations, although gene loss can also be generated through single nucleotide loss-of-funtion mutations.…”

Retrocopying expands the functional repertoire of APOBEC3 antiviral proteins in primates

“…However, there are well-documented examples of retrogenes that have been retained for their functionality (Casola and Betrán, 2017). To investigate whether any of the A3 retrocopies might be functional, we used several criteria to eliminate retrocopies likely to be non-functional.…”

“…These 'retrocopies' are intronless and removed from the chromosomal location of the parental intron-containing gene. Previous studies estimated that 3,700-18,000 retrocopies are present in the human genome (Casola and Betrán, 2017;Navarro and Galante, 2015;Potrzebowski et al, 2008).…”

“…For example, ribosomal proteins that are highly expressed in germline tissues represent the most abundant class of processed pseudogenes in the human genome (Balasubramanian et al, 2009). While germline expression of host mRNAs predicates the generation of retrocopies, the vast majority of these show characteristic signatures of 4 pseudogenization (Casola and Betrán, 2017;Navarro and Galante, 2015;Potrzebowski et al, 2008).…”