Protein-Coding Genes’ Retrocopies and Their Functions

Abstract

Transposable elements, often considered to be not important for survival, significantly contribute to the evolution of transcriptomes, promoters, and proteomes. Reverse transcriptase, encoded by some transposable elements, can be used in trans to produce a DNA copy of any RNA molecule in the cell. The retrotransposition of protein-coding genes requires the presence of reverse transcriptase, which could be delivered by either non-long terminal repeat (non-LTR) or LTR transposons. The majority of these copies are in a state of “relaxed” selection and remain “dormant” because they are lacking regulatory regions; however, many become functional. In the course of evolution, they may undergo subfunctionalization, neofunctionalization, or replace their progenitors. Functional retrocopies (retrogenes) can encode proteins, novel or similar to those encoded by their progenitors, can be used as alternative exons or create chimeric transcripts, and can also be involved in transcriptional interference and participate in the epigenetic regulation of parental gene expression. They can also act in trans as natural antisense transcripts, microRNA (miRNA) sponges, or a source of various small RNAs. Moreover, many retrocopies of protein-coding genes are linked to human diseases, especially various types of cancer.

An ABBA-BABA Test for Introgression Using Retroposon Insertion Data

“…The singularity of each retroposon insertion nullifies problems derived from the recombination ratchet. Third, retroposons are largely neutral markers (Kuritzin et al 2016;Chuong et al 2017;Kubiak and Makalowska 2017;Doronina et al 2019) as is assumed by summary coalescent methods (Liu et al 2009). More specifically, the overwhelming majority of retroposon insertions occur in genomic 'safe havens' where they have no known functional or selective significance (Kuritzin et al 2016;Chuong et al 2017).…”

FGF4retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs

“…A survey of retrogenes in the canine reference genome reported ~70 functional retrogenes in the dog; however, only the previous CFA18 FGF4 retrogene insertion has been reported to be associated with a disease causing phenotype 26,45 . Similarly in humans, the formation of processed pseudogenes in general, as well as those that retain their intended function and cause disease, is rare [46][47][48][49][50][51] .…”

Retrotransposons Manipulating Mammalian Skeletal Development in Chondrocytes

“…In contrast, class 1 mobile genetic elements include a number of active retrotransposons that are able to modify our genome structure. These retrotransposons are classified into two major groups; one is long terminal repeat (LTR) type, and the other is non-LTR type [2,5]. Both groups contain autonomous retrotransposons that can copy and paste themselves using their own devices, and non-autonomous retrotransposons that can replicate only under the assistance of the autonomous ones.…”

“…During the transitional era from the RNA world to the DNA world, the DNA-RNA-DNA replication cycle must have been the central process to form and enlarge the DNA genome. Following this classical genome manufacturing strategy, retrotransposons have constructed our genome over several hundred million years [5].…”