Evolution depends on rare chance events, ‘molecular time travel’ experiments show
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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 June 16, online in Nature. “This very important protein exists only because of a twist of fate,” said study senior author Joe Thornton, PhD, professor of ecology & evolution and human genetics at the University of Chicago. “If our results are general – and we think they probably are – then many of our body’s systems work as they do because of very unlikely chance events that happened in our deep evolutionary past,” he added. Thornton specializes in ancestral protein reconstruction, a technique that uses gene sequencing and computational methods to travel backwards through the evolutionary tree and infer the likely sequences of proteins as they existed in the deep past. Through biochemical methods, these ancient proteins can be synthesized and introduced into living organisms to study their function. Thornton and others have previously shown that the evolution of modern-day proteins required permissive mutations in the past. But no one had ever investigated whether there were many or few other possible permissive mutations that could have happened, so it remained unknown how unlikely it is that evolution discovered a permissive pathway to the modern function. (via Evolution depends on rare chance events, ‘molecular time travel’ experiments show)
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