Scientists theorized that they could manipulate a protein one mutation at a time and predict its evolution. They sought to prove it. And failed. They do think, however, that they’ve found a fundamental truth underlying unpredictability in a biological system.
Basic physical limitations make uncertainty the norm, they reported in a paper published online Oct. 23 in the Proceedings of the National Academy of Sciences.
“While we got a surprising negative result, we were able to say why,” said Michael J. Harms, a professor in the UO Department of Chemistry and Biochemistry and scientist in the Institute of Molecular Biology. “That is a positive. Our simple study provides confirmation of what many people in the field have observed repeatedly — unpredictability. It appears it is universal.”
The research was a digital affair, done with computer simulations designed by UO doctoral student Zachary R. Sailer. He and Harms created a simple lattice protein, using an approach previously created in the Harms lab, with a random sequence of 12 amino acids. They then ran evolutionary simulations to optimize stability, a physical property of the protein.
The goal was to use the effects of all 228 mutations known to be associated with the starting protein to predict these simulated trajectories: which mutation would occur, when, over time. The ability to project ahead faded fast after the first two mutations. After that, the anticipated trajectories went astray amid a growing number of rerouting probabilities.
“The quality of your information actually decays over time,” Sailer said. “As mutations accumulate, the effects of the mutations that you measured start to change so that you can’t predict where you are going.”
In their paper, Sailer and Harms suggest that physics, particularly thermodynamics, is at play. Each mutation alters the protein in a small, but nonlinear way. This means that the effect of each mutation depends on all mutations that occurred before.
“I think that what we showed, fundamentally, is that even if you know a lot about a system, about a protein, you cannot predict how it evolves because of the physics of the system,” Harms said. “There are physical rules that limit evolution and its predictability.”
How proteins evolve is a fundamental question in evolutionary biology, from both a philosophical perspective, to learn more about the machinery of biological systems, and for clues that might lead to improved or better drugs.Paper. (paywall) – Zachary R. Sailer, Michael J. Harms. Molecular ensembles make evolution unpredictable. Proceedings of the National Academy of Sciences, 2017; 201711927 DOI: 10.1073/pnas.1711927114 More.
This is not good news for evolutionary biology’s demand to be regarded as a dogma, enforced on the wrld, with portentous worries about the fact that so many people doubt.
But that just means that the history of life is no different than, for example, human history. Instead of history becoming a science, some sciences will become more like history in that detailed evidence must be assembled for each specific statement. Grand generalities are fine but they are the stuff of breakfast clubs, not research.
Note: Evolution News & Views’s take here:
The problem of evolving a protein is difficult for several reasons. First, protein function drops off rapidly with only a few mutations. Very quickly a protein loses its function as you move away from the native sequence.
Second, random or starting sequences are stuck in a flat and rugged fitness landscape. There is little sign of the kind of smooth and gradually increasing fitness landscape that would aid evolution’s enormous task of figuring out how proteins could evolve.
These problems are just getting worse, and this new finding is a good illustration of that trend.More.
All true. But at this point, “evolution” is mostly not a scientific enterprise any more. It is mostly a form of culture warfare to defend naturalism (nature is all there is). We see that in a vast variety of pretensions, everything from Canada’s new governor general’s driveby ridicule of anyone who doubts naturalism up to the illogical ramblings of a world-class poseur like pop science philosopher Daniel Dennett. When evolution get back to being a science again it will likely make more progress.
See also: Darwin’s aliens: Natural selection is magic. In other words, the theory is pure Darwinism, unbounded by reality— the notion that natural selection is a mystical but not intelligent creative force that creates complex, specified beings. We have never observed that but no matter, the theory fills a need: design without intelligence. Like magic, it just happens.