ABSTRACTMany regulatory networks involve (possibly partially) redundant cis-regulatory elements. These elements are commonly referred to as shadow enhancers and have been assumed to mainly originate by sequence duplication. An alternative mechanism that has not been examined involves the independent exaptation of transposons. Here, we identified 2,117 and 2,787 pairs of shadow enhancers in the human and mouse genomes, respectively, and found that 34% and 18% of these pairs derive from transposons. Moreover, we show that virtually all the enhancer partners of these transposon-derived shadow enhancer pairs are independent exaptations from different transposon types and hypothesize that the increase in the expression and tissue-specificity of their targets as compared to those of non-shadow enhancers facilitates their fixation in the genome. Finally, we provide evidence that the regulatory redundancy observed in many mammalian regulatory networks is predominantly driven by convergent evolution, since shadow enhancers are hardly ever conserved across species.
Independent transposon exaptation is a widespread mechanism of shadow enhancer evolution in the mammalian genome