The New York Times
, September 29, 2009Link
Evolutionary biologists have long wondered if history can run backward. Is it possible for the proteins in our bodies to return to the old shapes and jobs they had millions of years ago?
Examining the evolution of one protein, a team of scientists declares the answer is no, saying new mutations make it practically impossible for evolution to reverse direction. “They burn the bridge that evolution just crossed,” said Joseph W. Thornton, a biology professor at the University of Oregon and co-author of a paper on the team’s findings in the current issue of Nature.
The Belgian biologist Louis Dollo was the first scientist to ponder reverse evolution. “An organism never returns to its former state,” he declared in 1905, a statement later dubbed Dollo’s law.
To see if he was right, biologists have reconstructed evolutionary history. In 2003, for example, a team of scientists studied wings on stick insects. They found that the insects’ common ancestor had wings, but some of its descendants lost them. Later, some of those flightless insects evolved wings again.
Yet this study did not necessarily refute Dollo’s law. The stick insects may indeed have evolved a new set of wings, but it is not clear whether this change appeared as reverse evolution at the molecular level. Did the insects go back to the exact original biochemistry for building wings, or find a new route, essentially evolving new proteins?
Dr. Thornton and his colleagues took a close look at the possibility of reverse evolution at this molecular level. They studied a protein called a glucocorticoid receptor that helps humans and most other vertebrates cope with stress by grabbing a hormone called cortisol and then switching on stress-defense genes.
By comparing the receptor to related proteins, the scientists reconstructed its history. Some 450 million years ago, it started out with a different shape that allowed it to grab tightly to other hormones, but only weakly to cortisol. Over the next 40 million years, the receptor changed shape, so that it became very sensitive to cortisol but could no longer grab other hormones.
During those 40 million years, Dr. Thornton found, the receptor changed in 37 spots, only 2 of which made the receptor sensitive to cortisol. Another 5 prevented it from grabbing other hormones. When he made these 7 changes to the ancestral receptor, it behaved just like a new glucocorticoid receptor.
Dr. Thornton reasoned that if he carried out the reverse operation, he could turn a new glucocorticoid receptor into an ancestral one. So he and his colleagues reversed these key mutations to their old form.
To Dr. Thornton’s surprise, the experiment failed. “All we got was a completely dead receptor,” he said.
To figure out why they could go forward but not backward, Dr. Thornton and his colleagues looked closely again at the old and new receptors. They discovered five additional mutations that were crucial to the transition. If they reversed these five mutations as well, the new receptor behaved like an old one.
Based on these results, Dr. Thornton and his colleagues concluded that the evolution of the receptor unfolded in two chapters. In the first, the receptor acquired the seven key mutations that made it sensitive to cortisol and not to other hormones. In the second, it acquired the five extra mutations, which Dr. Thornton called “restrictive” mutations.
These restrictive mutations may have fine-tuned how the receptor grabbed cortisol. Or they may have had no effect at all. In either case, these five mutations added twists and tails to the receptor. When Dr. Thornton tried to return the receptor to its original form, these twists and tails got in the way.
Dr. Thornton argues that once the restrictive mutations evolved, they made it practically impossible for the receptor to evolve back to its original form. The five key mutations could not be reversed first, because the receptor would be rendered useless. Nor could the seven restrictive mutations be reversed first. Those mutations had little effect on how the receptor grabbed hormones. So there was no way that natural selection could favor individuals with reversed mutations.
For now it is an open question whether other proteins have an equally hard time evolving backward. But Dr. Thornton suspects they do.
“I would never say evolution is never reversible,” Dr. Thornton said. But he thinks it can only go backward when the evolution of the trait is simple, like when a single mutation is involved. When new traits are produced by several mutations that influence one another, he argues, that complexity shuts off reverse evolution. “We know that kind of complexity is very common,” he said.
If this molecular Dollo’s law holds up, Dr. Thornton believes it says something important about the course of evolutionary history. Natural selection can achieve many things, but it is hemmed in. Even harmless, random mutations can block its path.
“The biology we ended up with was not inevitable,” he said. “It was just one roll of the evolutionary dice.”
Copyright 2009 The New York Times Company. Reprinted with permission.