High-throughput Selection of Human de novo-emerged sORFs with High Folding Potential

0585603 - ÚOCHB 2025 RIV US eng J - Journal Article
Aubel, M. - Buchel, F. - Heames, B. - Jones, A. - Honc, O. - Bornberg-Bauer, E. - Hlouchová, Klára
High-throughput Selection of Human de novo-emerged sORFs with High Folding Potential.
Genome Biology and Evolution. Roč. 16, č. 4 (2024), č. článku evae069. ISSN 1759-6653. E-ISSN 1759-6653
Research Infrastructure: e-INFRA CZ II - 90254
Institutional support: RVO:61388963
Keywords : evolution * origin * genes
Impact factor: 3.3, year: 2022
Method of publishing: Open access
https://doi.org/10.1093/gbe/evae069

De novo genes emerge from previously noncoding stretches of the genome. Their encoded de novo proteins are generally expected to be similar to random sequences and, accordingly, with no stable tertiary fold and high predicted disorder. However, structural properties of de novo proteins and whether they differ during the stages of emergence and fixation have not been studied in depth and rely heavily on predictions. Here we generated a library of short human putative de novo proteins of varying lengths and ages and sorted the candidates according to their structural compactness and disorder propensity. Using Forster resonance energy transfer combined with Fluorescence-activated cell sorting, we were able to screen the library for most compact protein structures, as well as most elongated and flexible structures. We find that compact de novo proteins are on average slightly shorter and contain lower predicted disorder than less compact ones. The predicted structures for most and least compact de novo proteins correspond to expectations in that they contain more secondary structure content or higher disorder content, respectively. Our experiments indicate that older de novo proteins have higher compactness and structural propensity compared with young ones. We discuss possible evolutionary scenarios and their implications underlying the age-dependencies of compactness and structural content of putative de novo proteins.
Permanent Link: https://hdl.handle.net/11104/0353293