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bioRxiv · 10.1101/2021.04.13.439703

Intergenic ORFs as elementary structural modules of de novo gene birth and protein evolution

Papadopoulos, C.·Callebaut, I.·Gelly, J.-C.·Hatin, I.·Namy, O.·Renard, M.·Lespinet, O.·Lopes, A.
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Abstract

The noncoding genome plays an important role in de novo gene birth and in the emergence of genetic novelty. Nevertheless, how noncoding sequences properties could promote the birth of novel genes and shape the evolution and the structural diversity of proteins remains unclear. Therefore, by combining different bioinformatic approaches, we characterized the fold potential diversity of the amino acid sequences encoded by all intergenic ORFs (Open Reading Frames) of S. cerevisiae with the aim of (i) exploring whether the large structural diversity observed in proteomes is already present in noncoding sequences, and (ii) estimating the potential of the noncoding genome to produce novel protein bricks that can either give rise to novel genes or be integrated into pre-existing proteins, thus participating in protein structure diversity and evolution. We showed that amino acid sequences encoded by most yeast intergenic ORFs contain the elementary building blocks of protein structures. Moreover, they encompass the large structural diversity of canonical proteins with strikingly the majority predicted as foldable. Then, we investigated the early stages of de novo gene birth by identifying intergenic ORFs with a strong translation signal in ribosome profiling experiments and by reconstructing the ancestral sequences of 70 yeast de novo genes. This enabled us to highlight sequence and structural factors determining de novo gene emergence. Finally, we showed a strong correlation between the fold potential of de novo proteins and the one of their ancestral amino acid sequences, reflecting the relationship between the noncoding genome and the protein structure universe.

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Papadopoulos, C., Callebaut, I., Gelly, J.-C., Hatin, I., Namy, O., Renard, M., Lespinet, O., Lopes, A.. 2021-04-13. Intergenic ORFs as elementary structural modules of de novo gene birth and protein evolution. https://doi.org/10.1101/2021.04.13.439703

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