Liver-specific enhancers evolved from independent episodes of MITE domestication in Xenopus tropicalis

Transposable elements (TEs) occupy a significant fraction of a wide variety of eukaryotic genomes and can be domesticated into functional sequences harbouring a coding or regulatory potential. While studies in mammals have revealed that retrotransposons can frequently give rise to tissue-specific transcriptional enhancers our understanding of this phenomenon in other vertebrate groups is scarcer. Here, we examined TE occupancy at tissue-specific nucleosome free regions (NFRs) which are not annotated as promoters in the amphibian model organism Xenopus tropicalis. We report three distinct miniature inverted-repeat TEs (MITEs) enriched at distal liver-specific NFRs and belonging to the hAT, Harbinger and Kolobok superfamilies of DNA transposons. These MITEs show a marked depletion at NFRs specific to the bone tissue, probably reflecting a process of negative selection. In addition, we show that they are enriched for transcription factor binding sites known to be bound by key regulators of liver biology, hematopoiesis, and the immune system, and that they are more likely to be located in the vicinity of genes specifically expressed in the liver than other MITE copies that are not associated to a NFR. We also find that these MITEs are not present at orthologous positions in the genome of the related allotetraploid frog Xenopus laevis, while they globally are abundant in this species. We discuss how independent bursts of MITE amplification followed by subsequent domestication episodes might independently have given rise to liver-specific transcriptional enhancers in the Xenopus tropicalis lineage.