DNA Transposons Favor De Novo Transcript Emergence Through Enrichment of Transcription Factor Binding Motifs

The files containing processed data is available in the Zenodo archive https://doi.org/10.5281/zenodo.8403184, and is referred in the main text as “Supplemental Deposit”. Supplemental figures, information, analyses and models are found in the Supplementary Information (SI). All programs are stored on GitHub (https://github.com/MarieLebh). The position frequency matices (PFM) of the studied motifs can be downloaded from https://jaspar2020.genereg.net/collection/POLII/ (Pol II database for core motifs) and https://jaspar2022.genereg.net/downloads/ (tFBS motifs, download the insect core non redundant database).

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anglais. De novo genes emerge from noncoding regions of genomes via succession of mutations. Among others, such mutations activate transcription and create a new open reading frame (ORF). Although the mechanisms underlying ORF emergence are well documented, relatively little is known about the mechanisms enabling new transcription events. Yet, in many species a continuum between absent and very prominent transcription has been reported for essentially all regions of the genome. In this study, we searched for de novo transcripts by using newly assembled genomes and transcriptomes of seven inbred lines of Drosophila melanogaster, originating from six European and one African population. This setup allowed us to detect sample specific de novo transcripts, and compare them to their homologous nontranscribed regions in other samples, as well as genic and intergenic control sequences. We studied the association with transposable elements (TEs) and the enrichment of transcription factor motifs upstream of de novo emerged transcripts and compared them with regulatory elements. We found that de novo transcripts overlap with TEs more often than expected by chance. The emergence of new transcripts correlates with regions of high guanine-cytosine content and TE expression. Moreover, upstream regions of de novo transcripts are highly enriched with regulatory motifs. Such motifs are more enriched in new transcripts overlapping with TEs, particularly DNA TEs, and are more conserved upstream de novo transcripts than upstream their ‘nontranscribed homologs’. Overall, our study demonstrates that TE insertion is important for transcript emergence, partly by introducing new regulatory motifs from DNA TE families. Significance: In the present study, we used inbred lines of Drosophila melanogaster to detect earlier stages of de novo emerged transcripts in samples. We determined and studied the impact of transposable elements (TEs) and TFBS motifs on the emergence of de novo transcripts. We show that the insertion of DNA transposons plays a role in de novo transcripts emergence. We demonstrate enrichment of transcription factor binding motif (motifs whose identity to a reference motif is low) upstream de novo transcripts compared to regions upstream annotated genes and control non transcribed intergenic sequences.This enrichment is even more frequent upstream de novo transcripts overlapping with DNA TEs. Our findings help elucidate main molecular drivers of transcription gain, namely insertions of DNA TEs and enrichment in transcription factor motifs with lower similarity to the reference.Graphical Abstract: https://academic.oup.com/view-large/figure/476385418/evae134_ga.jpg