ArticleMolecular biology and evolution2021
Natural Selection on the Phase-Separation Properties of FUS during 160 My of Mammalian Evolution.
Article in Molecular biology and evolution, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 38 citations in OpenAlex.
- Protein-protein interaction network architecture of human polygenic traits reveals domain-spanning connectivity and evolutionary pressures.Genome biology · 2026Article
- Evolution of intrinsically disordered regions in vertebrate galectins for phase separation.EMBO reports · 2026Article
- Biomolecular phase separation in tumorigenesis: from aberrant condensates to therapeutic vulnerabilities.Molecular cancer · 2025Review
- Expanding the molecular grammar of polar residues and arginine in FUS phase separation.Nature chemical biology · 2025Article
- Scale-free Spatio-temporal Correlations in Conformational Fluctuations of Intrinsically Disordered Proteins.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Rapid evolutionary change in trait correlations of single proteins.Nature communications · 2024Article
- Phosphorylation sites are evolutionary checkpoints against liquid-solid transition in protein condensates.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- RNA granules: functional compartments or incidental condensates?Genes & development · 2023Review
- Molecular and environmental determinants of biomolecular condensate formation.Nature chemical biology · 2022Review
- Two Conserved Amino Acids Characterized in the Island Domain Are Essential for the Biological Functions of Brassinolide Receptors.International journal of molecular sciences · 2022Article
- The physics of liquid-to-solid transitions in multi-domain protein condensates.Biophysical journal · 2022Article
- Discovering molecular features of intrinsically disordered regions by using evolution for contrastive learning.PLoS computational biology · 2022Article
- Post-translational modifications in liquid-liquid phase separation: a comprehensive review.Molecular biomedicine · 2022Review
- The return of the rings: Evolutionary convergence of aromatic residues in the intrinsically disordered regions of RNA-binding proteins for liquid-liquid phase separation.Protein science : a publication of the Protein Society · 2022Article
- Phylogenetic convergence of phase separation and mitotic function in the disordered protein BuGZ.Protein science : a publication of the Protein Society · 2022Article
- Deciphering how naturally occurring sequence features impact the phase behaviours of disordered prion-like domains.Nature chemistry · 2022Article
- Evolution of sequence traits of prion-like proteins linked to amyotrophic lateral sclerosis (ALS).PeerJ · 2022Article
- Liquid-Liquid Phase Separation of TDP-43 and FUS in Physiology and Pathology of Neurodegenerative Diseases.Frontiers in molecular biosciences · 2022Review
- Karyopherin abnormalities in neurodegenerative proteinopathies.Brain : a journal of neurology · 2021Review
- Targeted modulation of protein liquid-liquid phase separation by evolution of amino-acid sequence.PLoS computational biology · 2021Article
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Authors and funding
2 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein phase separation can help explain the formation of many nonmembranous organelles. However, we know little about its ability to change in evolution. Here we studied the evolution of the mammalian RNA-binding protein Fused in Sarcoma (FUS), a protein whose prion-like domain (PLD) contributes to the formation of stress granules through liquid-liquid phase separation. Although the PLD evolves three times as rapidly as the remainder of FUS, it harbors absolutely conserved tyrosine residues that are crucial for phase separation. Ancestral reconstruction shows that the phosphorylation sites within the PLD are subject to stabilizing selection. They toggle among a small number of amino acid states. One exception to this pattern is primates, where the number of such phosphosites has increased through positive selection. In addition, we find frequent glutamine to proline changes that help maintain the unstructured state of FUS that is necessary for phase separation. Our work provides evidence that natural selection has stabilized the liquid forming potential of FUS and minimized the propensity of cytotoxic liquid-to-solid phase transitions during 160 My of mammalian evolution.
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