Unravelling the Evolution of Complexes with Ancestral Sequence Reconstruction
This project aims to investigate the evolutionary processes behind protein complex formation and maintenance, testing the roles of natural selection and neutral evolution across three model systems.
Projectdetails
Introduction
Almost all proteins perform their functions as part of protein complexes. These assemblies are intricate and often beautiful examples of evolution's capacity to generate complexity. But are they built by natural selection? My recent work has revealed that they may in fact be produced and maintained across vast time scales by neutral processes, even if they provide no adaptive benefit at all.
Objectives
In this proposal, I will test this radical idea by bringing together ancestral sequence reconstruction and quantitative biochemistry of protein complexes. I will use this approach to experimentally unravel the evolutionary processes that generate and maintain biochemical complexity in three model systems that exemplify archetypical protein-protein interactions:
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First Objective
I will unravel what drives the evolutionary gain and loss of homomeric interactions. I will recapitulate how the universally conserved enzyme citrate synthase repeatedly underwent changes in self-assembly state. I will test if these changes were adaptive or whether they resulted from new interfaces being highly evolvable. -
Second Objective
I will probe why protein complexes evolve to depend on transient interactions with folding and assembly chaperones. I will retrace how the CO2 fixing enzyme RubisCO acquired a set of dedicated assembly and folding chaperones. I will unravel whether the initial gain of new chaperone interactions was useful and determine what later caused RubisCO to start completely depending on them. -
Third Objective
I will unravel if many of the interactions between different complexes are caused by neutral evolution. I will use a new experimental approach in yeast to quantify the rate at which complexes gain interactions with the rest of the proteome by chance alone.
Conclusion
Together, these experiments will show for the first time how adaptive evolution and neutral processes interacted to produce the intricate biochemical complexity we see inside cells today.
Financiële details & Tijdlijn
Financiële details
Subsidiebedrag | € 1.485.013 |
Totale projectbegroting | € 1.485.013 |
Tijdlijn
Startdatum | 1-5-2022 |
Einddatum | 30-4-2027 |
Subsidiejaar | 2022 |
Partners & Locaties
Projectpartners
- PHILIPPS UNIVERSITAET MARBURGpenvoerder
- MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Land(en)
Vergelijkbare projecten binnen European Research Council
Project | Regeling | Bedrag | Jaar | Actie |
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Evolution of Biomolecular CondensatesThis project aims to uncover the evolutionary origins and mechanisms of protein localization in biomolecular condensates through mapping, reconstruction, and experimental evolution across the tree of life. | ERC Starting... | € 1.494.150 | 2024 | Details |
When enzymes join forces: unmasking a mitochondrial biosynthetic engineThis project aims to reconstitute and characterize a biosynthetic pathway for coenzyme Q within a metabolon, revealing enzyme interactions and evolutionary transitions in crowded cellular environments. | ERC Advanced... | € 2.107.750 | 2023 | Details |
Proteome diversification in evolutionPROMISE aims to decode protein sequences and structures using AI to understand their interactions and evolution, ultimately transforming big data into actionable biological insights. | ERC Consolid... | € 1.952.762 | 2023 | Details |
Deciphering co-translational protein folding, assembly and quality control pathways, in health and diseaseThis project aims to elucidate co-translational protein folding and degradation mechanisms to understand misfolding diseases and improve therapeutic strategies. | ERC Starting... | € 1.412.500 | 2022 | Details |
Mechanisms of co-translational assembly of multi-protein complexes
This project aims to uncover the mechanisms of co-translational protein complex assembly using advanced techniques to enhance understanding of protein biogenesis and its implications for health and disease.
Evolution of Biomolecular Condensates
This project aims to uncover the evolutionary origins and mechanisms of protein localization in biomolecular condensates through mapping, reconstruction, and experimental evolution across the tree of life.
When enzymes join forces: unmasking a mitochondrial biosynthetic engine
This project aims to reconstitute and characterize a biosynthetic pathway for coenzyme Q within a metabolon, revealing enzyme interactions and evolutionary transitions in crowded cellular environments.
Proteome diversification in evolution
PROMISE aims to decode protein sequences and structures using AI to understand their interactions and evolution, ultimately transforming big data into actionable biological insights.
Deciphering co-translational protein folding, assembly and quality control pathways, in health and disease
This project aims to elucidate co-translational protein folding and degradation mechanisms to understand misfolding diseases and improve therapeutic strategies.