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Control and coordination of eukaryotic gene expression rely on transcriptional and posttranscriptional regulatory networks. Evolutionary innovations and adaptations often require rapid changes of such networks. It has long been hypothesized that transposable elements (TE) might contribute to the rewiring of regulatory interactions. More recently it emerged that TEs might bring in ready-to-use transcription factor binding sites to create alterations to the promoters by which they were captured. A process where the gene regulatory architecture is of remarkable plasticity is sex determination. While the more downstream components of the sex determination cascades are evolutionary conserved, the master regulators can switch between groups of organisms even on the interspecies level or between populations. In the medaka fish ( Oryzias latipes ) a duplicated copy of  dmrt1 , designated  dmrt1bY  or  DMY , on the Y chromosome was shown to be the master regulator of male development, similar to  Sry  in mammals. We found that the  dmrt1bY  gene has acquired a new feedback downregulation of its expression. Additionally, the autosomal  dmrt1a  gene is also able to regulate transcription of its duplicated paralog by binding to a unique target Dmrt1 site nested within the  dmrt1bY  proximal promoter region. We could trace back this novel regulatory element to a highly conserved sequence within a new type of TE that inserted into the upstream region of  dmrt1bY  shortly after the duplication event. Our data provide functional evidence for a role of TEs in transcriptional network rewiring for sub- and/or neo-functionalization of duplicated genes. In the particular case of  dmrt1bY , this contributed to create new hierarchies of sex-determining genes.

Transcriptional Rewiring of the Sex Determining dmrt1 Gene Duplicate by Transposable Elements