Chance events may profoundly shape history. What if Franz Ferdinand’s driver had not taken a wrong turn, bringing the Duke face to face with his assassin? Would World War I still have been fought? Would Hitler have risen to power decades later? Historians can only speculate on what might have been, but a team of evolutionary biologists studying ancient proteins has turned speculation into experiment. They resurrected an ancient ancestor of an important human protein as it existed hundreds of millions of years ago and then used biochemical methods to generate and characterize a huge number of alternative histories that could have ensued from that ancient starting point.
Tracing these alternative evolutionary paths, the researchers discovered that the protein – the cellular receptor for the stress hormone cortisol – could not have evolved its modern-day function unless two extremely unlikely mutations happened to evolve first. These “permissive” mutations had no effect on the protein’s function, but without them the protein could not tolerate the later mutations that caused it to evolve its sensitivity to cortisol. In screening thousands of alternative histories, the researchers found no alternative permissive mutations that could have allowed the protein’s modern-day form to evolve. The researchers describe their findings in a recent online Nature issue.
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