Evolution depends on rare chance events, 'molecular time travel' experiments show

Jun 19, 2014 by Kevin Jiang
What might the world like today look like without rare, chance events that happened in the past? Credit: University of Chicago Medical Center

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 – 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.

To answer this question, Thornton and co-author Michael Harms, PhD, of the University of Oregon focused on the glucocorticoid receptor (GR), a key protein in the endocrine system that regulates development and stress responses in response to the hormone cortisol. They resurrected the gene for ancestral GR as it existed around 450 million years ago, before it evolved its capacity to specifically recognize cortisol. They included a handful of mutations that occurred slightly later that allowed the protein to evolve its cortisol recognition, but they left out the permissive mutations, rendering the protein nonfunctional.

Thornton and Harms then created millions of copies of this genetic template, using a method that introduced random mutations into every new copy, thus mimicking the variation that evolution could have produced in the protein under alternative scenarios. To identify permissive mutations in these "might-have-been" pathways, they engineered yeast cells that could grow only if they contained a functional GR and then introduced their "library" of mutated versions of ancestral GR into them. If any of the mutations were permissive, they would restore the GR's function and allow the yeast to grow when exposed to cortisol.

Thornton and Harms tested many thousands of variants but found none that restored the function of GR other than the historical mutations that occurred in actuality. "Among the huge numbers of alternate possible histories, there were no other permissive mutations that could have opened an evolutionary path to the modern-day GR," Thornton said.

By studying the effects of mutations on the ancient protein's physical architecture, Harms and Thornton also showed why permissive mutations are so rare. To exert a permissive effect, a mutation had to stabilize a specific portion of the – the same part destabilized by the function-switching mutations – without stabilizing other regions or otherwise disrupting the structure. Very few mutations, they showed, can satisfy all these narrow constraints.

"These results show that contingency—the influence of chance events on the way evolution unfolds—is built into the atomic structure of molecules," said Irene Eckstrand, Ph.D., of the National Institutes of Health's National Institute of General Medical Sciences, which provided substantial funding for the research. "If the results hold true for other systems, this will be a highly significant contribution to our understanding of exactly how proteins can evolve new functions—a process that accounts for the diversity of life and the origins of genetic variation."

While most prior discussions of historical contingency in evolution have focused on external events such as asteroid impacts, mass extinctions, climate change, Thornton and Harms showed that the intrinsic complexity of proteins as physical objects also makes evolution depend profoundly on low-probability chance events.

"It's very exciting to have been able to directly study alternative ancient histories," Thornton said. "If evolutionary history could be relaunched from ancestral starting points, we would almost certainly end up with a radically different biology from the one we have now. Unpredictable genetic events are constantly opening paths to some evolutionary outcomes and closing the paths to others, all within the biochemical systems of our cells.

Explore further: Natural born killers: Chimpanzee violence is an evolutionary strategy

More information: "Historical contingency and its biophysical basis in glucocorticoid receptor evolution," Nature (2014) DOI: 10.1038/nature13410

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orti
1.5 / 5 (4) Jun 19, 2014
Anthropic principle in life's evolution too?
Torbjorn_Larsson_OM
5 / 5 (5) Jun 19, 2014
Selection bias, certainly. Perhaps life emerged several times, but only one made it (through our universal common ancestor). We only know of the clades that made it until today or that has been seen as fossils. And some of the traits used today are contingent (as predicted by the theory describing the process).

The anthropic principle (AP), that the result is (normal) distributed around the most likely values for life, is harder to see. Maybe the cellular trait is such though, because we no longer see almost-life protocells (changed geophysics) and complex multicellular organisms on the other end of being cellular are so rare vs prokaryotes so we can as well not exist either. (Indeed, Archaea and Bacteria would survive without us.) The biosphere being mostly prokaryotes would then be AP in action.
katesisco
1 / 5 (13) Jun 19, 2014
Well, if my theory is correct this is what happens: the monopole phase of our sun (currently ongoing) was the original aspect of our magnetar Sol. Magnetars lose energy immediately and quickly. I propose the monopole/dipole halfway point was the Cambrian explosion of life, just enough energy to begin life and not enough to erase it completely. The monopole tightens cellular life and the dipole loosens it. The created life of the monopole sun was 'set' when the energy release occurred that marked the dipolar onset. The energy from this change was such that the looseness created a genetic 'openness' that allowed for mixing.
These long ago events of high energy release may have been when our Earth experienced expansion and the water migrated to the deep lithosphere. Now there is insufficient energy to make that happen.

Our enexplicable genetic heritage of" some have it and some don't" is explained by this constant introduction of monopole life and the later mingling.
Rustybolts
1 / 5 (3) Jun 19, 2014
Then you think about today and going forward. What quadrillions possibilities there will be with DNA altering chemicals, exploding and leaking nuclear reactors and lets not forget the possibility of biological warfare in the near future.
MP3Car
3.5 / 5 (2) Jun 19, 2014
I am not an expert on evolution, but please someone make sure I understand this correctly, and I apologize for this crude analogy in advance...

So they took an orange (equating an orange to human's GR response) as it exists today and "worked backwards" to make it identical to how it would have appeared 450MYA, let's say it was an apple. They determined that there was only one mutation that could have happened to get an apple to become an orange, calling it this "chance" mutation for how we got here... Isn't this idea easy to believe, and almost intuitive though? Just like they started the article out, "What if Franz Ferdinand's driver had not taken a wrong turn..." What if I left work 5 seconds earlier, I wouldn't have gotten in a car accident last year. The apple may not have become an orange, it may have become a pear. Evolution still would have happened, we just may be a little, or a lot, different from how we are now. Instead of cortisol, it may be a different hormone.
MP3Car
4.8 / 5 (4) Jun 19, 2014
I guess maybe there previously had been a widely accepted belief that there could have been many possible "roads" that would have led us to where we are, but this research shows that there was only one road??? I guess I just don't like the statement, "because of very unlikely chance" because there WERE other roads that may have had equal chances, but there was only one road that got us here, but the other equally likely roads could also have resulted in intelligent life, similar to what we have today, but the GR response may have been replaced by something totally different.
cjn
5 / 5 (9) Jun 19, 2014
I guess maybe there previously had been a widely accepted belief that there could have been many possible "roads" that would have led us to where we are, but this research shows that there was only one road??? I guess I just don't like the statement, "because of very unlikely chance" because there WERE other roads that may have had equal chances, but there was only one road that got us here, but the other equally likely roads could also have resulted in intelligent life, similar to what we have today, but the GR response may have been replaced by something totally different.


Not quite. Saying that there is only "one road" is only accurate if you are dictating the endstate. We make this mistake often by assuming that we (humans) are the endstate, and that the only road possible led to us. There were a nearly infinite other possible outcomes for life on Earth's evolution to now. Fortunately for us, the road that WAS taken was the road that resulted in human evolution.
Modernmystic
4 / 5 (2) Jun 19, 2014
I think one of the best philosophical arguments for evolution (not that it NEEDS anything further than the scientific evidence currently available) is that everything changes. It seems to be a universal truth that nothing stays the same in this universe. Even the cosmos as a whole is going through a series of changes and stages, why should life be any different?
orti
1 / 5 (11) Jun 19, 2014
We have a universe that popped into existence 13.7 bya – no one has a reasonable explanation. We have that universe full of parameters that makes life possible (i.e. anthropic principle) – you know the story. We have very complex life developing on at least one of its planets – no one has a reasonable explanation (other than the evolutionist's tautology of "well it did so it had to"). We have that life developing a consciousness that can contemplate the universe from which it sprang and wonder why – even more, no one has a reasonable (physical) explanation. This is getting monotonous.
rockwolf1000
3 / 5 (2) Jun 19, 2014

Not quite. Saying that there is only "one road" is only accurate if you are dictating the endstate. We make this mistake often by assuming that we (humans) are the endstate, and that the only road possible led to us. There were a nearly infinite other possible outcomes for life on Earth's evolution to now. Fortunately for us, the road that WAS taken was the road that resulted in human evolution.


Well said.

However you make yet another assumption, that of us being "fortunate". Perhaps if a different path had been taken we might all have wings, or immunity to cancer, or gills, or simpler childbirth, or less greed, or less violence. The possibilities are endless.

Of course things could be much worse also I suppose so perhaps "fortunate" is accurate!?!
MP3Car
5 / 5 (6) Jun 19, 2014
There were a nearly infinite other possible outcomes for life on Earth's evolution to now. Fortunately for us, the road that WAS taken was the road that resulted in human evolution.


That was my point, i guess I didn't state it very clearly. I felt the article implied there was only "one road" that would have worked. And maybe that is true if you're defining the "end-state" as humans/vertebrates/etc exactly as they are today, really more of a "present state" than end. I just didn't want creationists taking this article as proof that the chance of that one single road being taken was so minute, it must have been divine intervention. But the way I see it, there were multiple roads that could have been taken, infinite as you said.
skuysandsons
not rated yet Jun 19, 2014
I would add entropy, enthalpy, enzymes and catalysts to the guidance of the direction of evolution. It's not completely chance. It's chemistry, too. my humble thoughts
animah
5 / 5 (2) Jun 19, 2014
I don't think the journalist does the findings justice. Chance is a misleading term when talking about evolution.

Express change as a function of information density and time. Sure, the Cartesian product is learge. But there is a lot of chemistry in a cm3 of ocean, vast oceans, and eons of time.

So given enough time, everything that can happen will happen. What happens at any given time can be described as chance, but overall the effect is pretty systematic.
DonGateley
not rated yet Jun 19, 2014
Evert's non-collapsing many world quantum hypothesis yields us as we are, low probability notwithstanding, simply because it was possible. Everything that can happen does somewhere in that multiverse. And there are others that have the same guarantee (see Tegmark.)
JVK
1 / 5 (8) Jun 20, 2014
Excerpt: "...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."

My comment: Placing ecological variation and nutrient-dependent pheromone-controlled ecological adaptations into the context of biophysically-constrained molecular epigenetics but touting random mutations in the context of "evolution" seems silly. Cell type differentiation is most closely linked from the epigenetic landscape to the physical landscape of DNA in the organized genomes of all species via olfactory/pheromonal input.

Perhaps I've misinterpreted their claims and they already know that "Olfaction and odor receptors provide a clear evolutionary trail that can be followed from unicellular organisms to insects to humans..." Kohl (2012) http://www.socioa...ew/17338
JVK
1 / 5 (8) Jun 20, 2014
http://phys.org/n...firstCmt
Quantum biology: Algae evolved to switch quantum coherence on and off

"The ancestral cryptophyte alga acquired its chloroplast by engulfing and taming a red algal endosymbiont, which would have had at least a primitive phycobilisome (7, 24)."

That suggests a nutrient-dependent ecological adaptation to me. Who thinks "...engulfing and taming a red algal endosymbiont..." is an example of mutation-driven evolution? How can anyone be that ignorant when it comes to biologically based cause and effect?

You don't need to believe in the neo-Darwinian theories that were invented and defined to fit what you thinks is known. You need only compare what people like that think to the biological facts.

See: Replace the Modern Synthesis (Neo-Darwinism): An Interview With Denis Noble
and
Nutrient-dependent/pheromone-controlled adaptive evolution: a model.
qitana
not rated yet Jun 20, 2014
So World War I existed because of the cortisol... :)
aaronbarlow72
1 / 5 (3) Jun 20, 2014
So many 'chance' mutations that would be irreducibly complex. there is no reason for such mutations to survive.
Of course there's always an astronomical chance for it to occur.
The problem is the impossibility of the first cell occurring. There is irreducible complexity involved in DNA formation in aqueous environments. DNA breaks down in aqueous solutions. Then there is the need for ATP synthase to create energy (ATP) for DNA to function. ATP motors are coded by DNA which creates a chicken and egg quandary.
animah
5 / 5 (3) Jun 22, 2014
irreducibly complex

Old creationist quackery, debunked a thousand times. Just Google it or start at:

http://en.wikiped...mplexity
PhotonX
5 / 5 (3) Jun 22, 2014
Well, if my theory is correct this is what happens: the monopole phase of our sun (currently ongoing) was the original aspect of our magnetar Sol. Magnetars lose energy immediately and quickly. I propose the monopole/dipole halfway point was the Cambrian explosion of life, just enough energy to begin life and not enough to erase it completely. The monopole tightens cellular life and the dipole loosens it. The created life of the monopole sun was 'set' when the energy release occurred that marked the dipolar onset. The energy from this change was such that the looseness created a genetic 'openness' that allowed for mixing.
I'm not an astrophysicist, but I can't imagine how you think the Sun used to be a magnetar.
.
We have just got to get you together with bobbylon_5 over here: http://phys.org/n...ong.html It's a match made in heaven.
JVK
1 / 5 (5) Jun 22, 2014
http://www.nature...321.html

Their results integrate theoretical and experimental evidence that links sensory input to activity-dependent gene expression and to synaptic excitation and inhibition. Their insight into how two opposing synaptic inputs remain proportional in populations of differentiated cell types "...reveals an unanticipated degree of order in the distribution of synaptic strengths in cortical space." Therefore, anyone who believes that their brain evolved via accumulated mutations and natural selection may want to start planning what they will say when others also claim that ideas associated with neo-Darwinism are nothing more than pseudoscientific nonsense.
mogmich
not rated yet Jun 23, 2014
It is not mentioned in the article, but couldn't this explain the importance of sexual reproduction?

The permissive mutations are extremely unlikely, but also harmless. They don't make survival of the individual less likely. But sexual reproduction makes it much more likely that the mutation is actually present in a few individuals. If and when the mutation becomes favorable, it is already present in the population, and can spread itself very quickly. The result is a sudden change in the whole population. An important new property seems to appear "out of the blue".