"This very important protein exists only because of a twist of fate," says Joe Thornton. "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." (Credit: Henning Mühlinghaus/Flickr)

Did our evolution hinge on a ‘twist of fate’?

Chance events may profoundly shape history. We can speculate about alternative possibilities, 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 stress hormone cortisol—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 online in Nature.

‘Unlikely chance events’

“This very important protein exists only because of a twist of fate,” says study senior author Joe Thornton, 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 adds.

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.

Going back 450 million years

To answer this question, Thornton and co-author Michael Harms 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 says.

Permissive mutations are rare

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 protein—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 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.”

‘Radically different biology’

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 says.

“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.”

Source: University of Chicago

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  1. Babu G. Ranganathan

    NATURAL LIMITS TO EVOLUTION: Only micro-evolution, or evolution within biological “kinds,” is genetically possible (such as the varieties of dogs, cats, horses, cows, etc.), but not macro-evolution, or evolution across biological “kinds,” (such as from sea sponge to human). All real evolution in nature is simply the expression, over time, of already existing genes or variations of already existing genes. For example, we have breeds of dogs today that we didn’t have a few hundred years ago. The genes for these breeds had always existed in the dog population but never had opportunity before to be expressed. Only limited evolution or adaptation, variations of already existing genes and traits, is possible.

    The genes (chemical instructions or code) must first exist or otherwise the evolution cannot occur. Genes instruct the body to build our tissues and organs. Nature is mindless and has no ability to design and program entirely new genes for entirely new traits. Nature can only work with the genetic ability already existing in species. Nature cannot perform the genetic engineering necessary to increase that genetic ability.

    Many people have wrong ideas of how evolution is supposed to work. Physical traits and characteristics are determined and passed on by genes – not by what happens to our body parts. For example, if a woman were to lose her finger this wouldn’t affect how many fingers her baby will have. Changing the color and texture of your hair will not affect the color and texture of your children’s hair. So, even if an ape’s muscles and bones changed so that it could walk upright it still would not be able to pass on this trait to its offspring. Only changes or mutations that occur in the genetic code of reproductive cells (i.e. sperm and egg) can be passed on to offspring.

    Modern evolutionists believe and hope that over, supposedly, millions of years, random genetic mutations in the genes of reproductive cells caused by environmental radiation will generate entirely new genes. This is total blind and irrational faith on the part of evolutionists. It’s much like believing that randomly changing the sequence of letters in a romance novel, over millions of years, will turn it into a book on astronomy! That’s the kind of blind faith macro-evolutionists have.

    When evolutionary scientists teach that random genetic mutations in species over, supposedly, millions of years caused by random environmental agents such as radiation, produced entirely new genes (i.e. genetic code or genetic information) leading to entirely new forms of life, they are not teaching science but simply a faith, a belief!

    Mutations are accidents in the genetic, are mostly harmful, and have no capability of producing greater complexity in the code. Even if a good accident occurred, for every good one there would be hundreds of harmful ones with the net result, over time, being harmful, even lethal, to the species. At best, mutations only produce further variations within a natural species. Even so, mutations are not the best explanation for variations within a natural species.

    Since it is not rational to believe that genetic information, or any form of information, can arise by chance, it is totally rational to believe that God (the Supreme Genetic Engineer) placed within all natural species, in the beginning, with all of the recessive and dominant genes that produced all of the intra-species variations in nature.

    If life on earth had really existed for millions of years, all species would have become extinct by now due to the colossal number of accumulated mutations over time (please read the author’s popular Internet article, ARE FOSSILS REALLY MILLIONS OF YEARS OLD?).

    What about natural selection? Natural selection doesn’t produce biological traits or variations. It can only “select” from biological variations that are possible and which have survival value. The term “natural selection” is a figure of speech. Nature doesn’t do any conscious selecting. If a variation occurs in a species (i.e. change in skin color) that helps the species survive then that survival is called being “selected.” That’s all it is. Natural selection is a passive process in nature, not a creative process.

    How could species have survived if their vital tissues, organs, reproductive systems, etc. were still evolving? A partially evolved trait or organ that is not complete and fully functioning from the start would be a liability to a species, not a survival asset. Plants and animals in the process of macro-evolution would be unfit for survival. For example, “if a leg of a reptile were to evolve (over supposedly millions of years) into a wing of a bird, it would become a bad leg long before it became a good wing” (Dr. Walt Brown, scientist and creationist). Survival of the fittest actually would have prevented evolution across biological kinds! Read my Internet article: WAR AMONG EVOLUTIONISTS! (2nd Edition).

    All species of plants and animals in the fossil record are found complete, fully-formed, and fully functional. This is powerful evidence that species did not come into existence gradually by any macro-evolutionary process but, rather, came into existence as complete and ready-to-go from the very beginning, which is possible only by special creation.

    All the fossils that have been used to support human evolution have been found to be either hoaxes, non-human, or human, but not non-human and human (i.e. Neanderthal Man was discovered later to be fully human). Textbooks and museums still continue to display examples and illustrations supporting human evolution which most evolutionists have rejected and no longer support. Many diagrams of ape-man creatures over the years were reconstructed according to evolutionary interpretations from disputable bones that have now been discredited but still being taught in school textbooks.

    What about genetic and biological similarities between species? Genetic information, like other forms of information, cannot happen by chance, so it is more logical to believe that genetic and biological similarities between all forms of life are due to a common Designer who designed similar functions for similar purposes. It doesn’t mean all forms of life are biologically related! Only genetic similarities within a natural species proves relationship because it’s only within a natural species that members can interbreed and reproduce

    What about “Junk DNA?” It’s not junk. It’s we who were ignorant of their usefulness. These so-called “non-coding” segments of DNA have recently been shown to be vital in regulating gene expression (i.e. when, where, and how genes are expressed, so they’re not “junk”). Even more recent scientific evidence shows that they do code for proteins, after all, and that we need to readjust our thinking of how the cell reads the genetic code (Read “Human Proteome More Complex Than Previously Thought,” Internet article by Dr. Jeffrey Tomkins). Read my popular Internet article: HOW FORENSIC SCIENCE REFUTES ATHEISM

    The real issue is what biological variations are possible, not natural selection.

    Visit my latest Internet site: THE SCIENCE SUPPORTING CREATION .
    I discuss: Punctuated Equilibria, “Junk DNA,” genetics, mutations, natural selection, fossils, dinosaur “feathers,” the genetic and biological similarities between various species, etc., etc.

    Sincerely,
    Babu G. Ranganathan*
    (B.A. theology/biology)

    Author of popular Internet article, TRADITIONAL DOCTRINE OF HELL EVOLVED FROM GREEK ROOTS

    *I have had the privilege of being recognized in the 24th edition of Marquis “Who’s Who In The East” for my writings on religion and science. I have given successful lectures (with question and answer period afterward) before evolutionist science faculty and students at various colleges/universities.

  2. Babu G. Ranganathan

    NATURAL LIMITS TO EVOLUTION: Only micro-evolution, or evolution within biological “kinds,” is genetically possible (such as the varieties of dogs, cats, horses, cows, etc.), but not macro-evolution, or evolution across biological “kinds,” (such as from sea sponge to human). All real evolution in nature is simply the expression, over time, of already existing genes or variations of already existing genes. For example, we have breeds of dogs today that we didn’t have a few hundred years ago. The genes for these breeds had always existed in the dog population but never had opportunity before to be expressed. Only limited evolution or adaptation, variations of already existing genes and traits, is possible.

    The genes (chemical instructions or code) must first exist or otherwise the evolution cannot occur. Genes instruct the body to build our tissues and organs. Nature is mindless and has no ability to design and program entirely new genes for entirely new traits. Nature can only work with the genetic ability already existing in species. Nature cannot perform the genetic engineering necessary to increase that genetic ability.

    Many people have wrong ideas of how evolution is supposed to work. Physical traits and characteristics are determined and passed on by genes – not by what happens to our body parts. For example, if a woman were to lose her finger this wouldn’t affect how many fingers her baby will have. Changing the color and texture of your hair will not affect the color and texture of your children’s hair. So, even if an ape’s muscles and bones changed so that it could walk upright it still would not be able to pass on this trait to its offspring. Only changes or mutations that occur in the genetic code of reproductive cells (i.e. sperm and egg) can be passed on to offspring.

    Modern evolutionists believe and hope that over, supposedly, millions of years, random genetic mutations in the genes of reproductive cells caused by environmental radiation will generate entirely new genes. This is total blind and irrational faith on the part of evolutionists. It’s much like believing that randomly changing the sequence of letters in a romance novel, over millions of years, will turn it into a book on astronomy! That’s the kind of blind faith macro-evolutionists have.

    When evolutionary scientists teach that random genetic mutations in species over, supposedly, millions of years caused by random environmental agents such as radiation, produced entirely new genes (i.e. genetic code or genetic information) leading to entirely new forms of life, they are not teaching science but simply a faith, a belief!

    Mutations are accidents in the genetic, are mostly harmful, and have no capability of producing greater complexity in the code. Even if a good accident occurred, for every good one there would be hundreds of harmful ones with the net result, over time, being harmful, even lethal, to the species. At best, mutations only produce further variations within a natural species. Even so, mutations are not the best explanation for variations within a natural species.

    Since it is not rational to believe that genetic information, or any form of information, can arise by chance, it is totally rational to believe that God (the Supreme Genetic Engineer) placed within all natural species, in the beginning, with all of the recessive and dominant genes that produced all of the intra-species variations in nature.

    If life on earth had really existed for millions of years, all species would have become extinct by now due to the colossal number of accumulated mutations over time (please read the author’s popular Internet article, ARE FOSSILS REALLY MILLIONS OF YEARS OLD?).

    What about natural selection? Natural selection doesn’t produce biological traits or variations. It can only “select” from biological variations that are possible and which have survival value. The term “natural selection” is a figure of speech. Nature doesn’t do any conscious selecting. If a variation occurs in a species (i.e. change in skin color) that helps the species survive then that survival is called being “selected.” That’s all it is. Natural selection is a passive process in nature, not a creative process.

    How could species have survived if their vital tissues, organs, reproductive systems, etc. were still evolving? A partially evolved trait or organ that is not complete and fully functioning from the start would be a liability to a species, not a survival asset. Plants and animals in the process of macro-evolution would be unfit for survival. For example, “if a leg of a reptile were to evolve (over supposedly millions of years) into a wing of a bird, it would become a bad leg long before it became a good wing” (Dr. Walt Brown, scientist and creationist). Survival of the fittest actually would have prevented evolution across biological kinds! Read my Internet article: WAR AMONG EVOLUTIONISTS! (2nd Edition).

    All species of plants and animals in the fossil record are found complete, fully-formed, and fully functional. This is powerful evidence that species did not come into existence gradually by any macro-evolutionary process but, rather, came into existence as complete and ready-to-go from the very beginning, which is possible only by special creation.

    All the fossils that have been used to support human evolution have been found to be either hoaxes, non-human, or human, but not non-human and human (i.e. Neanderthal Man was discovered later to be fully human). Textbooks and museums still continue to display examples and illustrations supporting human evolution which most evolutionists have rejected and no longer support. Many diagrams of ape-man creatures over the years were reconstructed according to evolutionary interpretations from disputable bones that have now been discredited but still being taught in school textbooks.

    What about genetic and biological similarities between species? Genetic information, like other forms of information, cannot happen by chance, so it is more logical to believe that genetic and biological similarities between all forms of life are due to a common Designer who designed similar functions for similar purposes. It doesn’t mean all forms of life are biologically related! Only genetic similarities within a natural species proves relationship because it’s only within a natural species that members can interbreed and reproduce

    Also, so-called “Junk DNA” isn’t junk. Although these “non-coding” segments of DNA don’t code for proteins, they have recently been found to be vital in regulating gene expression (i.e. when, where, and how genes are expressed, so they’re not “junk”). Read my popular Internet article: HOW FORENSIC SCIENCE REFUTES ATHEISM

    The real issue is what biological variations are possible, not natural selection.

    Visit my latest Internet site: THE SCIENCE SUPPORTING CREATION .
    I discuss: Punctuated Equilibria, “Junk DNA,” genetics, mutations, natural selection, fossils, dinosaur “feathers,” the genetic and biological similarities between various species, etc., etc.

    Sincerely,
    Babu G. Ranganathan*
    (B.A. theology/biology)

    Author of popular Internet article, TRADITIONAL DOCTRINE OF HELL EVOLVED FROM GREEK ROOTS

    *I have had the privilege of being recognized in the 24th edition of Marquis “Who’s Who In The East” for my writings on religion and science. I have given successful lectures (with question and answer period afterward) before evolutionist science faculty and students at various colleges/universities.

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