Contingency and chance erase necessity in the experimental evolution of ancestral proteins
- University of Chicago, United States
Abstract
The roles of chance, contingency, and necessity in evolution is unresolved, because they have never been assessed in a single system or on timescales relevant to historical evolution. We combined ancestral protein reconstruction and a new continuous evolution technology to mutate and select B-cell-lymphoma-2-family proteins to acquire protein-protein-interaction specificities that occurred during animal evolution. By replicating evolutionary trajectories from multiple ancestral proteins, we found that contingency generated over long historical timescales steadily erased necessity and overwhelmed chance as the primary cause of acquired sequence variation; trajectories launched from phylogenetically distant proteins yielded virtually no common mutations, even under strong and identical selection pressures. Chance arose because many sets of mutations could alter specificity at any timepoint; contingency arose because historical substitutions changed these sets. Our results suggest that patterns of variation in BCL-2 sequences – and likely other proteins, too – are idiosyncratic products of a particular, unpredictable course of historical events.
Data availability
The high throughput sequencing data of evolved BCL-2 family protein variants were deposited in the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA) databases. They can be accessed via BioProject: PRJNA647218. The processed sequencing data are available on Dryad (https://doi.org/10.5061/dryad.866t1g1ns). The coding scripts and reference sequences for processing the data are available on Github (https://github.com/JoeThorntonLab/BCL2.ChanceAndContingency).
-
BCL2-Chance and ContingencyDryad Digital Repository, 10.5061/dryad.866t1g1ns.
Article and author information
Author details
Funding
National Institutes of Health (R01GM131128)
- Joseph W Thornton
National Institutes of Health (R01GM121931)
- Joseph W Thornton
National Institutes of Health (R01GM139007)
- Joseph W Thornton
National Institutes of Health (F32GM122251)
- Brian PH Metzger
National Science Foundation (DGE-1746045)
- Victoria Cochran Xie
National Science Foundation (1749364)
- Bryan C Dickinson
The content is solely the responsibility of the authors and the funders had no input on the study design, analysis, or conclusions.
Copyright
© 2021, Xie et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
