Multiple FGF4 Retrocopies Recently Derived within Canids

Abstract

Two transcribed retrocopies of the fibroblast growth factor 4 (<i>FGF4</i>) gene have previously been described in the domestic dog. An <i>FGF4</i> retrocopy on chr18 is associated with disproportionate dwarfism, while an <i>FGF4</i> 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 <i>FGF4</i> retrocopies that could be contributing to phenotypic diversity in canids. Additionally, dogs with surgically confirmed IVDD were assayed for novel <i>FGF4</i> retrocopies. Five additional and distinct <i>FGF4</i> retrocopies were identified in canids including a copy unique to red wolves (<i>Canis rufus</i>). The <i>FGF4</i> retrocopies identified in domestic dogs were identical to domestic dog <i>FGF4</i> haplotypes, which are distinct from modern wolf <i>FGF4</i> haplotypes, indicating that these retrotransposition events likely occurred after domestication. The identification of multiple, full length <i>FGF4</i> 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.