Useless evolution

It’s easy to focus on the big picture when one thinks of evolution: how organisms adapt and change over the march of time makes for pretty compelling study. But smaller evolutionary mechanisms are easily missed when looking at such a grand scale.

Not all evolutionary shifts are, as we imagine, a driving force for improvement. On close examination, some represent meaningless change.

“Nothing in evolution makes sense except in light of population genetics,” writes Michael Lynch, from the University of Indiana, US, in his 2007 paper “The frailty of adaptive hypotheses for the origins of organismal complexity”.

Lynch explains that we are taught genetics from a higher level, to see how genes change in a population over time. In reality, evolution isn’t an intelligent strategist that aims to make things better; rather, it’s a passive, multi-faceted process and product of the unchangeable rules of biochemistry.

Molecules operate the body to keep everything in a complicated balance, and these molecules experience evolutionary change, too. Many of these molecules must work together to form molecular machines, or complexes, which have classically been thought of as beneficial.

“How complexity evolves is one of the great questions of evolutionary biology,” says Joseph Thornton, of the University of Chicago, US. “The classic explanation is that elaborate structures must exist because they confer some functional benefit on the organism, so natural selection drives ever-increasing states of complexity.

“But at the molecular level, we found that there are other simple mechanisms that drive the build-up of complexity.”

This is known as constructive neutral evolution (CNE). A molecular mechanism may evolve even though it provides no benefit just because it also provides no disadvantage – it simply happens because of biochemical quirk.

CNE isn’t a new concept. It was proposed decades ago. But if we don’t know the practical function of an ancient protein, it’s really difficult to confirm whether an ancestral protein was inferior to contemporary proteins or not.

This is where modern technology helps. Thornton and colleagues tested how steroid receptor molecules evolved to form pairs called a dimer, which they explained in a paper recently published in Nature. They used an elegant method called ancestral sequence reconstruction, in which they recreated the ancient ancestor of the steroid receptors before they’d evolved to work as dimers. 

It turned out that the ancient proteins functioned just as well as the modern, intricate dimers, despite the solo protein being significantly simpler; it wouldn’t matter if they’d never evolved at all. There was nothing beneficial about forming the molecular machine, but it became a fixed trait due to an evolutionary fluke.

Ironically, the steroid receptors evolved to rely on a completely useless form because of biochemistry. In this case, it happened because proteins are made of amino acids, some of which dissolve in water, and some that are hydrophobic and dissolve in oil. Usually the protein shape “hides” hydrophobic molecules inside the protein, which protects it from dissolving in the oils in our body. But proteins that form dimers can keep these hydrophobic amino acids on the surface, because they’ll be hidden once the machine complex is formed. This, in turn, causes the single, unpaired molecules to break down as their hydrophobic molecules are exposed, so only the paired molecules can function.

Genes are always undergoing change. A process called purifying selection removes bad changes from the genome over time, but only harmful mutations are removed. This means that once the steroid receptors evolved to form a dimer, extra mutations that stopped the protein dimerising suddenly became detrimental and were lost during purifying selection. 

The original formation of the dimer wasn’t harmful, and so wasn’t lost during selection. But once it happened, the proteins just couldn’t go back to the older, simpler method, and the machines hung around for hundreds of millions of years. 

“These proteins gradually became addicted to their interaction, even though there is nothing useful about it,” explains Georg Hochberg of the Max Planck Institute, Germany. “The parts of the protein that form the interface where the partners bind each other accumulated mutations that were tolerable after the dimer evolved, but would have been deleterious in the solo state. This made the protein totally dependent on the dimeric form, and it could no longer go back. Useless complexity became entrenched, essentially forever.”

The researchers tested this method of evolution with thousands of proteins and found that the same thing kept happening. They called this mechanism a “hydrophobic ratchet”. It may be responsible for the sheer number of proteins that rely on forming complexes to work properly. The hydrophobic ratchet is a purely biochemical principal that influences how the proteins evolve, instead of an evolutionary principal such as natural selection or genetic drift. 

While it might sound bizarre, the original mutations that led to these machines might have been quite simple, too. 

For example, a six-protein machine that pumps protons through cell membranes may have formed due to minimal mutations. The machine, called the V-ATPase proton pump, is an extremely important complex in celled organisms. One part is made of three very closely related proteins that form a ring that interacts with other machines.

Researchers resurrected the ancient proteins using synthetic DNA and introduced a very simple mutation to the gene. This triggered a chain of reactions that led to descendant proteins working exactly as they do today, suggesting how little is actually needed for neutral mutations to become established in the genome.

At a small scale, there’s no “thought” of adaptation, there’s simply change based on chemistry and physics. At a higher, population scale, we can’t see these hidden complexities, so it all seems like adaptation. Quite simply, molecules are not intelligently evolved. 

Constructive neutral evolution is a beautiful theory that highlights exactly how complex evolution is, and that it goes well beyond “survival of the fittest”. Sometimes, things just uselessly evolve. 

Related reading: Genetic study shows evolution at work in modern humans

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