My postdoctoral advisor and I just published a paper in which we found that chance historical events determined the evolution of an important human protein. We statistically reconstructed an ancient ancestor of the human glucocorticoid receptor and then experimentally characterized “might-have-been” evolutionary trajectories. This screen revealed that very few mutations are compatible with the historically-realized evolutionary outcome, and that the evolution of this protein was contingent on the chance events that opened the historical path. If we were able to restart evolution from this ancestral protein, a radically different outcome would likely have been realized. Our results reveal that the current structures we observe in biology can be far from optimal, but instead depend on the peculiar evolutionary trajectory they took to reach their current form.
Published in Nature, 2014.