Gene regulatory networks and essential transcription factors for de novo originated genes

The regulation of gene expression is crucial for the functional integration of evolutionarily young genes, particularly those that emerge de novo. However, the regulatory programs governing the expression of de novo genes remain unknown. To address this, we applied computational methods to single-cell RNA sequencing data, identifying key transcription factors likely instrumental in regulating de novo genes. We found that transcription factors do not have the same propensity for regulating de novo genes; some transcription factors contain more de novo genes than others in their regulon. Leveraging genetic and genomic tools in Drosophila, we further examined the role of two key transcription factors and the regulatory architecture of novel genes. Our findings identify key transcription factors associated with the expression of de novo genes and provide new insights into how modifications in existing transcription factors enable the emergence, maintenance, and regulation of de novo genes.