Multiple FGF4 Retrocopies Recently Derived within Canids.

Kevin Batcher,Danika Bannasch,Peter Dickinson,Tosso Leeb,Cord Drögemüller,Kimberly Maciejczyk,Kristin Brzeski,Anna Letko,Sheida Hadji Rasouliha

doi:10.3390/genes11080839

Kevin Batcher, Danika Bannasch + Show 7 more

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https://doi.org/10.3390/genes11080839

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Abstract

Two transcribed retrocopies of the fibroblast growth factor 4 (FGF4) gene have previously been described in the domestic dog. An FGF4 retrocopy on chr18 is associated with disproportionate dwarfism, while an FGF4 retrocopy on chr12 is associated with both disproportionate dwarfism and intervertebral disc disease (IVDD). In this study, whole-genome sequencing data were queried to identify other FGF4 retrocopies that could be contributing to phenotypic diversity in canids. Additionally, dogs with surgically confirmed IVDD were assayed for novel FGF4 retrocopies. Five additional and distinct FGF4 retrocopies were identified in canids including a copy unique to red wolves (Canis rufus). The FGF4 retrocopies identified in domestic dogs were identical to domestic dog FGF4 haplotypes, which are distinct from modern wolf FGF4 haplotypes, indicating that these retrotransposition events likely occurred after domestication. The identification of multiple, full length FGF4 retrocopies with open reading frames in canids indicates that gene retrotransposition events occur much more frequently than previously thought and provide a mechanism for continued genetic and phenotypic diversity in canids.

Highlights

Gene retrocopies, often previously referred to as processed pseudogenes, are formed through the mRNA-mediated gene duplication of cellular gene transcripts [1]
Discordant paired end reads mapping from exon to exon (Supplemental Figure S1 shown in red) are indicative of the presence of an fibroblast growth factor 4 (FGF4) gene retrocopy somewhere in the genome as retrocopies lack introns, while discordant paired end reads, wherein one mate maps to the FGF4 gene locus and the other mate maps to another region of the genome, are indicative of the putative insertion site for an FGF4 retrocopy (Supplemental Figure S1 shown in teal)
Multiple recently transposed FGF4 retrocopies exist in canids in addition to the previously identified FGF4L1 and FGF4L2

Summary

Introduction

Often previously referred to as processed pseudogenes, are formed through the mRNA-mediated gene duplication of cellular gene transcripts [1]. In mammals, this process is mediated by long interspersed nuclear elements 1 (L1) acting in trans [2,3]. L1 insertion is accomplished through target primed reverse transcription, a process that results in duplication of genomic DNA at the insertion site, called a target site duplication (TSD) [5]. Retrocopy insertions can occur anywhere in the genome, the L1 machinery shows a preference for the TTAAAA consensus sequence as an insertion site [3,6]

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