UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology; Program in Bioinformatics and Integrative Biology

Publication Date


Document Type



Biochemistry | Bioinformatics | Computational Biology | Molecular Biology | Structural Biology


Sequence divergence of orthologous proteins enables adaptation to environmental stresses and promotes evolution of novel functions. Limits on evolution imposed by constraints on sequence and structure were explored using a model TIM barrel protein, indole-3-glycerol phosphate synthase (IGPS). Fitness effects of point mutations in three phylogenetically divergent IGPS proteins during adaptation to temperature stress were probed by auxotrophic complementation of yeast with prokaryotic, thermophilic IGPS. Analysis of beneficial mutations pointed to an unexpected, long-range allosteric pathway towards the active site of the protein. Significant correlations between the fitness landscapes of distant orthologues implicate both sequence and structure as primary forces in defining the TIM barrel fitness landscape and suggest that fitness landscapes can be translocated in sequence space. Exploration of fitness landscapes in the context of a protein fold provides a strategy for elucidating the sequence-structure-fitness relationships in other common motifs.

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Copyright © 2017, The Author(s).

DOI of Published Version



Nat Commun. 2017 Mar 6;8:14614. doi: 10.1038/ncomms14614. Link to article on publisher's site

Journal/Book/Conference Title

Nature communications

Related Resources

Link to Article in PubMed

PubMed ID


Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.



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