Contingency and chance erase necessity in the experimental evolution of ancestral proteins.

Victoria Cochran Xie,Bryan C Dickinson,Joseph W Thornton,Brian Ph Metzger,Jinyue Pu

doi:10.7554/elife.67336

Abstract

The roles of chance, contingency, and necessity in evolution are 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 proteins in the B-cell lymphoma-2 (BCL-2) family 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 and unpredictable course of historical events.

Highlights

The extent to which biological diversity is the necessary result of optimization by natural selection or the unpredictable product of random events and historical contingency is one of evolutionary biology’s most fundamental and unresolved questions (Gould, 1989; Jablonski, 2017; Ramsey and Pence, 2016; Travisano et al, 1995)
We first characterized the historical evolution of protein-protein interactions (PPIs) specificity in the B-cell lymphoma-2 (BCL-2) family using ancestral protein reconstruction (Figure 2-figure supplement 2)
We reconstructed the most recent common ancestor (AncMB1) of the two classes – a gene duplication that occurred before the last common ancestor of all animals – and 11 other ancestral proteins that existed along the lineages leading from AncMB1 to human BCL-2 and to human MCL-1 (Supplementary File 1)

Summary

INTRODUCTION

The extent to which biological diversity is the necessary result of optimization by natural selection or the unpredictable product of random events and historical contingency is one of evolutionary biology’s most fundamental and unresolved questions (Gould, 1989; Jablonski, 2017; Ramsey and Pence, 2016; Travisano et al, 1995). By comparing sequence outcomes among PACE replicates from the same starting point, we quantified the role of chance in the evolution of historically relevant molecular functions under strong and identical selection pressures; by comparing outcomes of PACE initiated from different starting points, we quantified the effect of contingency generated by the sequence changes that accumulated during these proteins’ histories. This design allowed us to characterize how these factors have changed over phylogenetic time and dissect the underlying genetic basis by which they emerged

RESULTS

DISCUSSION

MATERIALS AND METHODS

Data and Code Availability

Methods