Scientists recreate evolution of complexity using 'molecular time travel'

Much of what living cells do is carried out by "molecular machines" – physical complexes of specialized proteins working together to carry out some biological function. How the minute steps of evolution produced these constructions has long puzzled scientists, and provided a favorite target for creationists.

In a study published early online on January 8, in Nature, a team of scientists from the University of Chicago and the University of Oregon demonstrate how just a few small, high-probability mutations increased the complexity of a molecular machine more than 800 million years ago. By biochemically resurrecting ancient genes and testing their functions in modern organisms, the researchers showed that a new component was incorporated into the machine due to selective losses of function rather than the sudden appearance of new capabilities.

"Our strategy was to use 'molecular time travel' to reconstruct and experimentally characterize all the proteins in this molecular machine just before and after it increased in complexity," said the study's senior author Joe Thornton, PhD, professor of human genetics and & ecology at the University of Chicago, professor of biology at the University of Oregon, and an Early Career Scientist of the Howard Hughes Medical Institute.

"By reconstructing the machine's components as they existed in the deep past," Thornton said, "we were able to establish exactly how each protein's function changed over time and identify the specific genetic mutations that caused the machine to become more elaborate."

The study – a collaboration of Thornton's molecular evolution laboratory with the biochemistry research group of the UO's Tom Stevens, professor of chemistry and member of the Institute of Molecular Biology – focused on a molecular complex called the V-ATPase proton pump, which helps maintain the proper acidity of compartments within the cell.

One of the pump's major components is a ring that transports hydrogen ions across membranes. In most species, the ring is made up of a total of six copies of two different proteins, but in fungi a third type of protein has been incorporated into the complex.

To understand how the ring increased in complexity, Thornton and his colleagues "resurrected" the ancestral versions of the ring proteins just before and just after the third subunit was incorporated. To do this, the researchers used a large cluster of computers to analyze the gene sequences of 139 modern-day ring proteins, tracing evolution backwards through time along the Tree of Life to identify the most likely ancestral sequences. They then used biochemical methods to synthesize those ancient genes and express them in modern yeast cells.

Thornton's research group has helped to pioneer this molecular time-travel approach for single genes; this is the first time it has been applied to all the components in a .

The group found that the third component of the ring in Fungi originated when a gene coding for one of the subunits of the older two-protein ring was duplicated, and the daughter genes then diverged on their own evolutionary paths.

The pre-duplication ancestor turned out to be more versatile than either of its descendants: expressing the ancestral gene rescued modern yeast that otherwise failed to grow because either or both of the descendant ring protein genes had been deleted. In contrast, each resurrected gene from after the duplication could only compensate for the loss of a single ring protein gene.

The researchers concluded that the functions of the ancestral protein were partitioned among the duplicate copies, and the increase in complexity was due to complementary loss of ancestral functions rather than gaining new ones. By cleverly engineering a set of ancestral proteins fused to each other in specific orientations, the group showed that the duplicated proteins lost their capacity to interact with some of the other ring proteins. Whereas the pre-duplication ancestor could occupy five of the six possible positions within the ring, each duplicate gene lost the capacity to fill some of the slots occupied by the other, so both became obligate components for the complex to assemble and function.

"It's counterintuitive but simple: complexity increased because protein functions were lost, not gained," Thornton said. "Just as in society, complexity increases when individuals and institutions forget how to be generalists and come to depend on specialists with increasingly narrow capacities."

The research team's last goal was to identify the specific genetic mutations that caused the post-duplication descendants to functionally degenerate. By reintroducing historical mutations that occurred after the duplication into the ancestral protein, they found that it took only a single mutation from each of the two lineages to destroy the same specific functions and trigger the requirement for a three-protein ring.

"The mechanisms for this increase in complexity are incredibly simple, common occurrences," Thornton said. "Gene duplications happen frequently in cells, and it's easy for errors in copying to DNA to knock out a protein's ability to interact with certain partners. It's not as if evolution needed to happen upon some special combination of 100 mutations that created some complicated new function."

Thornton proposes that the accumulation of simple, degenerative changes over long periods of times could have created many of the complex molecular machines present in organisms today. Such a mechanism argues against the intelligent design concept of "irreducible complexity," the claim that molecular machines are too complicated to have formed stepwise through evolution.

"I expect that when more studies like this are done, a similar dynamic will be observed for the evolution of many molecular complexes," Thornton said.

"These really aren't like precision-engineered machines at all," he added. "They're groups of molecules that happen to stick to each other, cobbled together during evolution by tinkering, degradation, and good luck, and preserved because they helped our ancestors to survive."

Explore further

Evolution Of Irreducible Complexity Explained

More information: "Evolution of increased complexity in a molecular machine," appears in the January 18, 2012, issue of Nature, doi: 10.1038/nature10724
Journal information: Nature

Citation: Scientists recreate evolution of complexity using 'molecular time travel' (2012, January 8) retrieved 23 October 2019 from
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Jan 08, 2012
I'm going to laugh my *ss off when Creationists and Evolutionists find out they're BOTH right; and that Evolution IS God's method of perpetual Creation, making the world new at every stage. Now, kiss and make up; there are more important things to do than have a p*ssing contest over how the universe was made.

Jan 08, 2012
Argiod, there's a third perspective, toward which i lean, and it's this: Our creators are highly evolved life forms, who packaged our genetic programming with self-editing and self- repairing features.

Jan 08, 2012
@Argoid - I often paraphrase Bohr's comment to Einstein and ask anti-evolutionists who they think they are to tell god not to use evolution.

@Telekenetic - you are correct in one sense. Those 'highly evolved life forms' are previous generations of our genes. Life evolved to evolve, first learning to tolerate errors, then to fix errors more and more errors, and then to leave some errors in some places to provide variety for evolution to work on. That certainly is an incredibly intelligent design, but the 'intelligent designer' is the PROCESS of evolution itself, not some external entity.

Jan 08, 2012
@Argiod - It seems unlikely that both viewpoints can be right although it is true that evolution being the mechanism by which god creates speciation is (sort of) the position taken by some religions. Nevertheless, it is unnecessary to postulate that there is any such thing as (one or more) god; this idea also introduces complexity that is not needed and simply sets back at a further remove the question of origination. (The question being: How did the putative god or other creator arise? If asked [and I have], fundamentalist creationists will insist that their god has always existed but this introduces the ultimate, and perfect, "irreducable complexity" argument against them that they are so fond themselves of using against evolutionary theory, incorrectly I would add.)

Jan 08, 2012
Groups of molecules that happen to stick are credited with tinkering, degradation, and good luck during evolution. Does that mean each of our ancestors as far back as single-celled organisms was preserved because they helped our other ancestors to survive? If so, I have a problem with what appears to be a one-way model. For example, how does the accumulation of simple, degenerative changes over long periods of times cause speciation, which incorporates many of the complex molecular machines present in organisms today? I think the accumulation of simple, degenerative changes in different organisms must stop for one species to establish its ecological niche but don't see any explanation for stop-and-start degenerative changes. That's why one-way models of evolved complexity don't work for me, but especially when the "one way" is via degradation. For contrast, Lynch et al http://www.nature....917.pdf find no evidence for stepwise evolution.

Jan 08, 2012
"It's counterintuitive but simple: complexity increased because protein functions were lost, not gained," Thornton said. "Just as in society, complexity increases when individuals and institutions forget how to be generalists and come to depend on specialists with increasingly narrow capacities." - So, when it's dead it is at it's ultimate sophistication...yeah science.

Jan 08, 2012
"It's dead Jim...I'm a doctor not a physicist!"

Jan 09, 2012
This absurd idea could also be compared to your computer. . The more you take away from it's complexity and design, the more complex and intelligent it becomes. . That makes no sense whatsoever, and I, as a scientist, propose that the above idea is absolute idiocy at the highest level.. It goes against all known physical laws, first of all, and secondly, it is quite insulting to human conscious thought and intellect. If that ridiculous idea is true, then our brains should be made of sand by now, and likewise, infinitely intelligent at the same time. . makes no sense whatsoever. I shall submit a paper refuting this absurdity. I have much more to say concerning this preposterous idea; however I shall not waste energy on such nonsense.

Jan 09, 2012
In addition, the only point that I will agree upon, is that 'time travel' is indeed possible (although limited in scope and reliability) but not in the sense that time is actually a medium in which one may 'travel' through. Discuss, email, or schedule an appointment with me at the university for more in depth studies.

Jan 09, 2012
@RealScience "ask anti-evolutionists who they think they are to tell god not to use evolution."
The answer is simple - God himself makes it quite clear that he did NOT use evolution - everything was created in SIX days, not billions of years [go read Genesis 1 and Exodus 20:8-11].

It's not as if evolution needed to happen upon some special combination of 100 mutations that created some complicated new function.

Where did those original genes come from in the first place? The researchers have no idea, so any subsequent mutations and perceived increase in complexity are mute. The original material is so complex in and of itself that it defies ANY evolutionary explanation from the start. There is just no way to get there by random processes. Even the best research so far has failed to show how life can start by chance.

Jan 09, 2012
@Smashin_Z_1885 Computers are indeed a very good example of the same principle - if you take away a function of an integrated circuit, the more specialized the particular circuit gets. First computers had just one simple processor for every task, now you have processors with multiple specialized units - unit for calculation with floating point numbers, unit for vector processing, also multiple paralell processing cores, some of them can be specialized for graphics, audio etc. So while specific parts of the computer got specialized to one particular task (lost some of their functionality), the whole system got more complex.

@kevinrtrs "We do not fully understand how lightning gets created, so logically it must be God throwing them on us because we made him angry" The fact that science doesn't have an answer to a particular question doesn't mean it won't have it in the future. Also if we can't prove explanation A, it doesn't mean explanation B is the right answer.

Jan 09, 2012
complexity increased because protein functions were lost, not gained
Just natures way of saying 'It's not a bug, it's a feature...'

Jan 09, 2012
The real issue is that mere pairwise mechanical interaction in supposed entropic space and time cannot account for the willful noetic identity of mankind.

Jan 09, 2012
@kevinrtrs - why can't you accept that it was six 'eras' not six 'days'? Then you could be asking scientists how the bible described the big bang and the order species evolved long before science discovered these things.

(And if you insist on 'days', are you saying that your God isn't powerful enough to fast forward evolution in six days? Why do you place such limits on your God?)

Jan 09, 2012
I see some here have risen a step up in logic and say:
"Aha! I see now that evolution is god's way of creation."

You might try rising up a step further and observe:
"Aha! I now see how I constantly seek a rationalization for god."

Our existence does appear to involve a progressive series of possible random combinations with increasing complexity, but does it have to be a god driven thing? Historically, men have always assumed their individual gods were driving things they didn't understand. I bet you also assume your god looks like a human. A thoughtful contemplation of your anthropomorphism might help you delve further into your acquired belief in a god.

Jan 09, 2012
If you understand evolution you understand that the existence of "god" would be redundant to the process.

Abiogenesis, however, might be a decent place to plant your goal post (for now).

Jan 09, 2012
If you do actually believe the universe was created in 6 days, then you might want to consider the following thought experiment:
The 6-day version implies that the geographic strata and other evidence for a lengthy past were actually put there by god, to be eventually discovered by scientists, possibly to challenge their ability to believe, as you do.

If so, wouldnt it be just as conceivable that your god might have created the universe, as it is, just 50 years ago, with all of the memories and implied history intact? God could have even created this universe just 5 minutes ago - just as it is. With that type of creation belief, who knows when a historically complete illusion was created? If I was a creationist who thought rationally, I would have to consider that as no less a possibility.

Jan 09, 2012
@MandoZink - exactly - The explanation that the universe we see sprang up ~13.7 billion years ago is the simplest explanation, but not the only one. And Quantum Mechanics agrees that the universe could spring into existence fully formed, too, although is assigns an exceedingly small probability).

I prefer the simplest explanation, but I don't hold it against people who hold other views, as long as they don't push them on science boards without evidence or attack simpler explanations.

Jan 09, 2012
@MandoZink - I don't personally see the need for a god of the Judeo-Christian type at all. But religion and science would bicker a lot less if the religious types would just see evolution as one of their God's tools, and scientists would accept that 'god' is really just a 3-letter word for 'universe' (or multiverse).

Jan 15, 2012
If a god exists then the size of the universe would easily suggest he made other life forms, otherwise why is the universe so large and empty in terms of life.

A more realistic concept to our evolution even taking into account how long it took to evolve, we could have come from hitching a ride frozen on a meteorite as bacteria,then thrived here.

Far more believable than god having been involved, why would he be arsed anyway? He would be embarrassed to admit he created humans, specially when you look at youtube comments. Lol

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