Evolution is irreversible 鈥� at least at a molecular level. That鈥檚 the conclusion of a study tracing how we evolved a protein that helps us respond to stress. But the idea that there is no way back for proteins is being treated with caution by other evolutionary geneticists.
The team who carried out the protein research expect the same principle to apply to complex evolved traits, including those involved in body shape, behaviour and metabolism. 鈥淓volution does not return to the past, but must always move on to different future states,鈥� says of the University of Oregon.
He and his colleagues retraced the ancestry of the glucocorticoid receptor, the protein within cells that binds and responds to the stress hormone, cortisol.
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By re-creating the receptor before and after it evolved its modern function some 400 million years ago, they demonstrated that the more recent version can鈥檛 tolerate having the ancestral structure and function restored.
Ratchet system
The main obstacle is a series of five seemingly inconsequential mutations that function like a ratchet in a cog system, allowing motion forward but not back. These mutations, which occurred after the protein evolved its new function to bind to cortisol, would cause structural clashes within the protein if it were returned to its ancestral state.
The researchers created a 鈥渇amily tree鈥� of stress hormone receptors by analysing comparable gene sequences of the proteins from many present-day animals. They identified two pivotal ancestors for further study.
Thornton鈥檚 group then synthesised the ancient receptors, allowing their functions and structures to be studied in the lab.
The first, called AncGR1, existed in its ancestral form from about 450 million years ago. As well as binding cortisol, it could respond to other hormones such as aldosterone and deoxycorticosterone.
40 million years later
After a further 40 million years of evolution involving 37 mutations, a second ancient receptor emerged, called AncGR2. This, like the same protein in modern humans, could be activated only by cortisol.
Thornton and his colleagues successfully made the oldest ancestor, AncGR1, evolve into a cortisol-specific receptor by introducing seven 鈥渇orward鈥� mutations. These dramatically altered the protein鈥檚 structure at the same time. But when they tried reversing the same seven mutations in AncGR2, the protein no longer functioned.
鈥淲e were surprised to get a dead receptor that wouldn鈥檛 respond to any hormones, because those same states had existed in the protein a relatively short time before,鈥� says Thornton.
Burning bridges
The group found that five subsequent mutations in AncGR2, which gradually refined the receptor鈥檚 ability to respond exclusively to cortisol, were completely incompatible with the ancestral structure. 鈥淓ffectively, the five mutations burn the bridge evolution had just crossed,鈥� Thornton said.
Thornton says that because the study is on only one protein, it can鈥檛 reveal how many other proteins are irreversible too. But he argues that the number is likely to be large because the type of complex interactions between mutations that caused irreversibility in the evolution of the cortisol receptor are common.
The same may apply to traits that affect the outward appearance or behaviour of an animal, because these often involve complex structures and networks of genes that have emerged together, making a stepwise path backwards extremely unlikely.
鈥淭he problem with the irreversibility argument is that it is based on the idea that evolution occurs by jumping from one pure state to another in single steps, like a chemical manipulation,鈥� says of Indiana University in Bloomington.
鈥楻everse鈥� genes
Lynch says that in a real population of organisms facing selection pressure to re-acquire a previously lost trait by 鈥済oing backwards鈥�, there will be plenty of intermediate 鈥渞everse鈥� genes remaining in the pool, even ones that are deleterious.
Through the multitude of 鈥渂ackward鈥� routes likely to be available in such a large population, these intermediates could enable the population as a whole to work its way back to the original trait, Lynch says.
Nor is he convinced that complexity of structure invariably serves as an evolutionary ratchet. 鈥淐omplex adaptations, although requiring multiple steps, also offer multiple routes back and forth, which can compensate for the complexity,鈥� he says.
of University College Cork in Ireland agrees that there are many routes backward, not just the same way you arrived. The structural barriers to 鈥渞ewinding鈥� the cortisol receptor are high, 鈥渂ut it鈥檚 difficult to prove that it鈥檚 impossible to get around them鈥�, he says.
Journal reference: Nature, DOI: 10.1038/nature08249 (in press)
