Discovering evolutionary innovations by assessing variation and natural selection in protein tandem repeats

• Research unit: COST
• Project number: C16.0072

Key words (English)

protein tandem repeat; protein evolution; selection; evolutionary innovation; phylogeny; Markov model of codon substitution; protein design

Research programs (English)

COST-Action BM1405 - Non-globular proteins: from sequence to structure, function and application in molecular physiopathology

Short description (English)

Tandem repeats (TRs) are abundant in proteomes across all kingdoms of life. Having an impressive variety of sizes, structures and functions, TRs often offer enhanced binding properties and are associated with disease and immunity related functions. While mechanisms generating protein TRs are poorly understood, natural selection contributes to shaping their evolution, and TR expansion may be linked to the origin of novel genes. Specific combinations of TR units with point mutations/indels are able to ensure desirable protein properties. Indeed, the design-ability of domain TRs has been successfully exploited in bioengineering. However, the experimental search for optimal TR configurations is difficult/inefficient due to the huge number of possible combinations. We will address this by modeling the evolution and natural selection in naturally observed proteins with domain TRs. Combined with annotations of structure, function and protein-protein interactions, we will pinpoint the naturally occuring evolutionary innovations, i.e., TR configurations that have been fixed by selection due to adaptive benefits. These predictions can serve as testable hypotheses in protein engineering experiments, allowing to narrow down the search to combinations with optimal properties according to the natural evolution history. For ankyrin and armadillo repeats, employed to design medically relevant proteins, specific recommendations will be made for further experimental testing.

Further information (English)

Full name of research-institution/enterprise: Zürcher Hochschule für Angewandte Wissenschaften ZHAW Life Sciences and Facility Management Institute of Applied Simulations, Head of Applied Computational Genomics

Partners and International Organizations (English)

AT; BE; HR; CY; CZ; DK; FI; FR; DE; EL; HU; IE; IL; IT; LV; LT; NO: PL; PT; RS; SK; SI; ES; SE; TR; UK; BA; RU; AR

Abstract (English)

See short description

References in databases (English)

Swiss Database: COST-DB of the State Secretariat for Education and Research Hallwylstrasse 4 CH-3003 Berne, Switzerland Tel. [phone] Swiss Project-Number: C16.0072