Thursday, 21th April, 2022, 12:00

Novel genes enable protein structural innovation and function in the brain

PRBB Computational Genomics Seminars, Chair: Gabriel Santpere (Head of Neurogenomics Group). How genuinely new protein-coding genes originate is a central question in biology. Long thought impossible to arise from non-coding sequence, novel genes arising de novo from genomic "junk" DNA or from long non-coding RNA were recently found in eukaryotic genomes. Novel genes are taxon-restricted and may encode structurally novel proteins with new protein domains. To understand how novel genes arise, we built a mathematical model based on gene and genome parameters and dynamic factors such as mutation. We combined phylostratigraphy and proteogenomics to identify novel genes in 25 eukaryotic genomes and evaluated their predicted biophysical properties. Compared to ancient proteins, novel proteins are shorter, more fragile, disordered and promiscuous, yet less prone to aggregate or to form toxic prions. We performed biophysical experiments comparing novel and ancient proteins, showed that novel genes function in vivo in zebrafish brains, and found novel genes are expressed in human brains at multiple ages. Genomic sequence turnover generates many novel genes encoding short proteins, of which some are maintained and encode proteins with distinct structural features and expressed in the brain. Thus, genomic variation continuously generates new protein structures and new functions. Zoom webinar: https://us02web.zoom.us/j/81073249721 / Password: 788137

Speaker: Victor Luria; Yale University, Department of Neuroscience, New Haven, USA. Harvard Medical School, Department of Systems Biology, Boston, USA.

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