Evolutionary origins of protein novelty across an entire yeast subphylum
- 1Hellenic Pasteur Institute
Abstract
Novel protein-coding sequences fuel molecular and cellular evolutionary innovations and frequently contribute to species-defining characteristics. They can originate either de novo from previously noncoding sequences or through extreme divergence of already coding ones. How frequently each mechanism occurs and how they shape the structural and functional potential of the resulting proteins remains unclear. Here, we conducted a broad computational investigation of genetic and protein novelty throughout the entire subphylum of Saccharomycotina yeasts. We detected more than 5,000 robust de novo genes across 332 species and compared them to more than 6,000 novel genes resulting from extreme sequence divergence, revealing two quantitatively similar but qualitatively distinct modes of evolution of novelty. A remarkable 40% of de novo proteins are predicted to localize to mitochondria compared to only 20% of divergent, with the latter also being substantially longer and more disordered. A detailed analysis of conservatively predicted tertiary structures of novel proteins shows that ''invention'' of new folds occurs more frequently through de novo emergence. We also illustrate cases of evolutionary ''re-invention'' of existing protein folds from noncoding sequences. Our work deepens our understanding of the origins and importance of novel proteins, opening new directions for further structural and functional characterization.
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BibTeX
@misc{tassios2026evolutionary,
title = {{Evolutionary origins of protein novelty across an entire yeast subphylum}},
author = {E. Tassios and N. Pyrgelis and D. Rinker and E. M. Tzermpou and C. T. Hittinger and A. Rokas and C. Nikolaou and N. Vakirlis},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.29.748005},
url = {https://www.biorxiv.org/content/10.64898/2026.08.29.748005v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Evolutionary origins of protein novelty across an entire yeast subphylum
AU - E. Tassios
AU - N. Pyrgelis
AU - D. Rinker
AU - E. M. Tzermpou
AU - C. T. Hittinger
AU - A. Rokas
AU - C. Nikolaou
AU - N. Vakirlis
PY - 2026
DA - 2026/08/29
PB - bioRxiv
DO - 10.64898/2026.08.29.748005
UR - https://www.biorxiv.org/content/10.64898/2026.08.29.748005v1
AB - Novel protein-coding sequences fuel molecular and cellular evolutionary innovations and frequently contribute to species-defining characteristics. They can originate either de novo from previously noncoding sequences or through extreme divergence of already coding ones. How frequently each mechanism occurs and how they shape the structural and functional potential of the resulting proteins remains unclear. Here, we conducted a broad computational investigation of genetic and protein novelty throughout the entire subphylum of Saccharomycotina yeasts. We detected more than 5,000 robust de novo genes across 332 species and compared them to more than 6,000 novel genes resulting from extreme sequence divergence, revealing two quantitatively similar but qualitatively distinct modes of evolution of novelty. A remarkable 40% of de novo proteins are predicted to localize to mitochondria compared to only 20% of divergent, with the latter also being substantially longer and more disordered. A detailed analysis of conservatively predicted tertiary structures of novel proteins shows that ''invention'' of new folds occurs more frequently through de novo emergence. We also illustrate cases of evolutionary ''re-invention'' of existing protein folds from noncoding sequences. Our work deepens our understanding of the origins and importance of novel proteins, opening new directions for further structural and functional characterization.
ER -