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.
Metrics
-
- 7,010
- views
-
- 977
- downloads
-
- 36
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Contingency and chance erase necessity in the experimental evolution of ancestral proteins
eLife 10:e67336.
https://doi.org/10.7554/eLife.67336
Further reading
-
- Computational and Systems Biology
- Evolutionary Biology
As pathogens spread in a population of hosts, immunity is built up, and the pool of susceptible individuals are depleted. This generates selective pressure, to which many human RNA viruses, such as influenza virus or SARS-CoV-2, respond with rapid antigenic evolution and frequent emergence of immune evasive variants. However, the host’s immune systems adapt, and older immune responses wane, such that escape variants only enjoy a growth advantage for a limited time. If variant growth dynamics and reshaping of host-immunity operate on comparable time scales, viral adaptation is determined by eco-evolutionary interactions that are not captured by models of rapid evolution in a fixed environment. Here, we use a Susceptible/Infected model to describe the interaction between an evolving viral population in a dynamic but immunologically diverse host population. We show that depending on strain cross-immunity, heterogeneity of the host population, and durability of immune responses, escape variants initially grow exponentially, but lose their growth advantage before reaching high frequencies. Their subsequent dynamics follows an anomalous random walk determined by future escape variants and results in variant trajectories that are unpredictable. This model can explain the apparent contradiction between the clearly adaptive nature of antigenic evolution and the quasi-neutral dynamics of high-frequency variants observed for influenza viruses.
-
- Ecology
- Evolutionary Biology
Understanding the origins of novel, complex phenotypes is a major goal in evolutionary biology. Poison frogs of the family Dendrobatidae have evolved the novel ability to acquire alkaloids from their diet for chemical defense at least three times. However, taxon sampling for alkaloids has been biased towards colorful species, without similar attention paid to inconspicuous ones that are often assumed to be undefended. As a result, our understanding of how chemical defense evolved in this group is incomplete. Here, we provide new data showing that, in contrast to previous studies, species from each undefended poison frog clade have measurable yet low amounts of alkaloids. We confirm that undefended dendrobatids regularly consume mites and ants, which are known sources of alkaloids. Thus, our data suggest that diet is insufficient to explain the defended phenotype. Our data support the existence of a phenotypic intermediate between toxin consumption and sequestration — passive accumulation — that differs from sequestration in that it involves no derived forms of transport and storage mechanisms yet results in low levels of toxin accumulation. We discuss the concept of passive accumulation and its potential role in the origin of chemical defenses in poison frogs and other toxin-sequestering organisms. In light of ideas from pharmacokinetics, we incorporate new and old data from poison frogs into an evolutionary model that could help explain the origins of acquired chemical defenses in animals and provide insight into the molecular processes that govern the fate of ingested toxins.
