ArticleScientific reports2017
Random protein sequences can form defined secondary structures and are well-tolerated in vivo.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- Emergence and evolution of protein-coding de novo genes.Nature reviews. Genetics · 2026Review
- Orthologs of an essential orphan gene vary in their capacities for function and subcellular localization in Drosophila melanogaster.Molecular biology and evolution · 2026Article
- Impact of GC content on de novo gene birth.Nature communications · 2026Article
- Emergence of antiphage functions from random sequence libraries reveals mechanisms of gene birth.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Expression of Random Sequences and de novo Evolved Genes From the Mouse in Human Cells Reveals Functional Diversity and Specificity.Genome biology and evolution · 2024Article
- De Novo Genes.Annual review of genetics · 2024Review
- Peptides En Route from Prebiotic to Biotic Catalysis.Accounts of chemical research · 2024Article
- Sequence, Structure, and Functional Space of Drosophila De Novo Proteins.Genome biology and evolution · 2024Article
- High-throughput Selection of Human de novo-emerged sORFs with High Folding Potential.Genome biology and evolution · 2024Article
- Selection of a de novo gene that can promote survival of Escherichia coli by modulating protein homeostasis pathways.Nature ecology & evolution · 2023Article
- Toxin rescue by a random sequence.Nature ecology & evolution · 2023Article
- Xeno Amino Acids: A Look into Biochemistry as We Do Not Know It.Life (Basel, Switzerland) · 2023Review
- Article
- Experimental characterization of de novo proteins and their unevolved random-sequence counterparts.Nature ecology & evolution · 2023Article
- On the Origins of Enzymes: Phosphate-Binding Polypeptides Mediate Phosphoryl Transfer to Synthesize Adenosine Triphosphate.Journal of the American Chemical Society · 2023Article
- Early Selection of the Amino Acid Alphabet Was Adaptively Shaped by Biophysical Constraints of Foldability.Journal of the American Chemical Society · 2023Article
- Intergenic Regions of Saccharomycotina Yeasts are Enriched in Potential to Encode Transmembrane Domains.Molecular biology and evolution · 2023Article
- Simple mechanisms for the evolution of protein complexity.Protein science : a publication of the Protein Society · 2022Review
- Heterologous expression of naturally evolved putative de novo proteins with chaperones.Protein science : a publication of the Protein Society · 2022Article
- The Origins and Functions of De Novo Genes: Against All Odds?Journal of molecular evolution · 2022Review
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The protein sequences found in nature represent a tiny fraction of the potential sequences that could be constructed from the 20-amino-acid alphabet. To help define the properties that shaped proteins to stand out from the space of possible alternatives, we conducted a systematic computational and experimental exploration of random (unevolved) sequences in comparison with biological proteins. In our study, combinations of secondary structure, disorder, and aggregation predictions are accompanied by experimental characterization of selected proteins. We found that the overall secondary structure and physicochemical properties of random and biological sequences are very similar. Moreover, random sequences can be well-tolerated by living cells. Contrary to early hypotheses about the toxicity of random and disordered proteins, we found that random sequences with high disorder have low aggregation propensity (unlike random sequences with high structural content) and were particularly well-tolerated. This direct structure content/aggregation propensity dependence differentiates random and biological proteins. Our study indicates that while random sequences can be both structured and disordered, the properties of the latter make them better suited as progenitors (in both in vivo and in vitro settings) for further evolution of complex, soluble, three-dimensional scaffolds that can perform specific biochemical tasks.
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