PRBB Computational Genomics Seminars Chris Papadopoulos

22/10/202612:00R_473.10_AULAPRBB Computational Genomics SeminarsChris PapadopoulosHospital del Mar Research Institute, Evolutionary genomics groupBeyond the Annotated Genome: Discovering Novel Microproteins in YeastAbstract:
For decades, gene duplication and divergence was considered the main mechanism driving the emergence of new genes. However, another mechanism called de novo gene birth has gained increasing attention. In this process, new genes emerge from previously non-coding regions of the genome that gradually acquire the ability to be transcribed and translated.
In our work, we investigate how new genes emerge and evolve across the Saccharomyces genus. We generated comprehensive reference transcriptomes for seven Saccharomyces species using deep long-read direct RNA sequencing. Focusing on S. cerevisiae, we identified more than 1,500 previously unannotated transcripts, which we then explore in an evolutionary context across the seven species.
We integrated more than 60 ribosome profiling datasets, identifying over 1000 open reading frames (ORFs) within these novel transcripts with evidence of translation. Using state-of-the-art deep learning tools, we predicted the mean ribosome loading capacity of 5' UTRs and found that translated transcripts possess sequence features upstream of the ORF that favor translation initiation.
Finally, we experimentally investigated the natural expression of microproteins encoded by selected translated ORFs and used knockout experiments to explore their potential functional impact under normal growth and stress conditions.
Together, our results reveal a pervasive and dynamic layer of previously unannotated transcription and translation in Saccharomyces. By tracing these sequences from their evolutionary origins to their translation and potential phenotypic effects, we aim to better understand how new genes emerge and how young microproteins may contribute to cellular function.