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ZBED  genes originate from domesticated  hAT  DNA transposons and encode regulatory proteins of diverse function in vertebrates. Here we reveal the evolutionary relationship between  ZBED  genes and demonstrate that they are derived from at least two independent domestication events in jawed vertebrate ancestors. We show that ZBEDs form two monophyletic clades, one of which has expanded through several independent duplications in host lineages. Subsequent diversification of  ZBED  genes has facilitated regulation of multiple diverse fundamental functions. In contrast to known examples of transposable element exaptation, our results demonstrate a novel unprecedented capacity for the repeated utilization of a family of transposable element-derived protein domains sequestered as regulators during the evolution of diverse host gene functions in vertebrates. Specifically, ZBEDs have contributed to vertebrate regulatory innovation through the donation of modular DNA and protein interacting domains. We identify that C7ORF29, ZBED2, 3, 4, and ZBEDX form a monophyletic group together with ZBED6, that is distinct from ZBED1 genes. Furthermore, we show that ZBED5 is related to Buster DNA transposons and is phylogenetically separate from other ZBEDs. Our results offer new insights into the evolution of regulatory pathways, and suggest that DNA transposons have contributed to regulatory complexity during genome evolution in vertebrates.

ZBED Evolution: Repeated Utilization of DNA Transposons as Regulators of Diverse Host Functions