Tag: molecular evolution

Biochemical Synonyms Restate the Case for a Creator

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BY FAZALE RANA – MARCH 13, 2019

Sometimes I just can’t help myself. I know it’s clickbait but I click on the link anyway.

A few days ago, as a result of momentary weakness, I found myself reading an article from the ScoopWhoop website, “16 Things Most of Us Think Are the Same but Actually Aren’t.”

OK. OK. Now that you saw the title you want to click on the link, too.

To save you from wasting five minutes of your life, here is the ScoopWhoop list:

  • Weather and Climate
  • Turtle and Tortoise
  • Jam and Jelly
  • Eraser and Rubber
  • Great Britain and the UK
  • Pill and Tablet
  • Shrimp and Prawn
  • Butter and Margarine
  • Orange and Tangerine
  • Biscuits and Cookies
  • Cupcakes and Muffins
  • Mushrooms and Toadstools
  • Tofu and Paneer
  • Rabbits and Hares
  • Alligators and Crocodiles
  • Rats and Mice

And there you have it. Not a very impressive list, really.

If I were putting together a biochemist’s version of this list, I would start with synonymous mutations. Even though many life scientists think they are the same, studies indicate that they “actually aren’t.”

If you have no idea what I am talking about or what this insight has to do with the creation/evolution debate, let me explain by starting with some background information, beginning with the central dogma of molecular biology and the genetic code.

Central Dogma of Molecular Biology

According to this tenet of molecular biology, the information stored in DNA is functionally expressed through the activities of proteins. When it is time for the cell’s machinery to produce a particular protein, it copies the appropriate information from the DNA molecule through a process called transcription and produces a molecule called messenger RNA(mRNA). Once assembled, mRNA migrates to the ribosome, where it directs the synthesis of proteins through a process known as translation.

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Figure 1: The central dogma of molecular biology. Image credit: Shutterstock

The Genetic Code

At first glance, there appears to be a mismatch between the stored information in DNA and the information expressed in proteins. A one-to-one relationship cannot exist between the four different nucleotides that make up DNA and the twenty different amino acids used to assemble proteins. The cell handles this mismatch by using a code comprised of groupings of three nucleotides, called codons, to specify the twenty different amino acids.

 

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Figure 2: Codons. Image credit: Wikipedia

The cell uses a set of rules to relate these nucleotide triplet sequences to the twenty amino acids that comprise proteins. Molecular biologists refer to this set of rules as the genetic code. The nucleotide triplets represent the fundamental units of the genetic code. The code uses each combination of nucleotide triplets to signify an amino acid. This code is essentially universal among all living organisms.

Sixty-four codons make up the genetic code. Because the code only needs to encode twenty amino acids, some of the codons are redundant. That is, different codons code for the same amino acid. In fact, up to six different codons specify some amino acids. Others are specified by only one codon.1

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Figure 3: The genetic code. Image credit: Shutterstock

A little more background information about mutations will help fill out the picture.

Mutations

A mutation refers to any change that takes place in the DNA nucleotide sequence. DNA can experience several different types of mutations. Substitution mutations are one common type. When a substitution mutation occurs, one (or more) of the nucleotides in the DNA strand is replaced by another nucleotide. For example, an A may be replaced by a G, or a C may be replaced by a T. This substitution changes the codon. Interestingly, the genetic code is structured in such a way that when substitution mutations take place, the resulting codon often specifies the same amino acid (due to redundancy) or an amino acid that has similar chemical and physical properties to the amino acid originally encoded.

Synonymous and Nonsynonymous Mutations

When substitution mutations generate a new codon that specifies the same amino acid as initially encoded, it’s referred to as a synonymous mutation. However, when a substitution produces a codon that specifies a different amino acid, it’s called a nonsynonymous mutation.

Nonsynonymous mutations can be deleterious if they affect a critical amino acid or if they significantly alter the chemical and physical profile along the protein chain. If the substituted amino acid possesses dramatically different physicochemical properties from the native amino acid, it may cause the protein to fold improperly. Improper folding impacts the protein’s structure, yielding a biomolecule with reduced or even lost function.

On the other hand, biochemists have long thought that synonymous mutations have no effect on protein structure and function because these types of mutations don’t change the amino acid sequences of proteins. Even though biochemists think that synonymous mutations are silent—having no functional consequences—evolutionary biologists find ways to use them, including using patterns of synonymous mutations to establish evolutionary relationships.

Patterns of Synonymous Mutations and the Case for Biological Evolution

Evolutionary biologists consider shared genetic features found in organisms that naturally group together as compelling evidence for common descent. One feature of particular interest is the identical (or nearly identical) DNA sequence patterns found in genomes. According to this line of reasoning, the shared patterns arose as a result of a series of substitution mutations that occurred in the common ancestor’s genome. Presumably, as the varying evolutionary lineages diverged from the nexus point, they carried with them the altered sequences created by the primordial mutations.

Synonymous mutations play a significant role in this particular argument for common descent. Because synonymous mutations don’t alter the amino acid sequence of proteins, their effects are considered to be inconsequential. So, when the same (or nearly the same) patterns of synonymous mutations are observed in genomes of organisms that cluster together into the same group, most life scientists interpret them as compelling evidence of the organisms’ common evolutionary history.

It is conceivable that nonsynonymous mutations, which alter the protein amino acid sequences, may impart some type of benefit and, therefore, shared patterns of nonsynonymous changes could be understood as evidence for shared design. (See the last section of this article.) But this is not the case when it comes to synonymous mutations, which raises the question: Why would a Creator intentionally introduce new codons that code for the same amino acid into genes when these changes have no functional utility?

Apart from invoking a Creator, the shared patterns of synonymous mutations make perfect sense if genomes have been shaped by evolutionary processes and an evolutionary history. However, this argument for biological evolution (shared ancestry) and challenge to a creation model interpretation (shared design) hinges on the underlying assumption that synonymous mutations have no functional consequence.

But what if this assumption no longer holds?

Synonymous Mutations Are Not Interchangeable

Biochemists used to think that synonymous mutations had no impact whatsoever on protein structure and, hence, function, but this view is changing thanks to studies such as the one carried out by researchers at University of Colorado, Boulder.2

These researchers discovered synonymous mutations that increase the translational efficiency of a gene (found in the genome of Salmonella enterica). This gene codes for an enzyme that plays a role in the biosynthetic pathway for the amino acid arginine. (This enzyme also plays a role in the biosynthesis of proline.) They believe that these mutations alter the three-dimensional structure of the DNA sequence near the beginning of the coding portion of the gene. They also think that the synonymous mutations improve the stability of the messenger RNA molecule. Both effects would lead to greater translational efficiency at the ribosome.

As radical (and unexpected) as this finding may seem to be, it follows on the heels of other recent discoveries that also recognize the functional importance of synonymous mutations.3Generally speaking, biochemists have discovered that synonymous mutations function to influence not only the rate and efficiency of translation (as the scientists from the University of Colorado, Bolder learned) and the folding of the proteins after they are produced at the ribosome.

Even though synonymous mutations leave the amino acid sequence of the protein unchanged, they can exert influence by altering the:

  • regulatory regions of the gene that influence the transcription rate
  • secondary and tertiary structure of messenger RNA that influences the rate of translation
  • stability of messenger RNA that influences the amount of protein produced
  • translation rate that influences the folding of the protein as it exits the ribosome

Biochemists are just beginning to come to terms with the significance of these discoveries, but it is already clear that synonymous mutations have biomedical consequences.4 They also impact models for molecular evolution. But for now, I want to focus on the impact these discoveries has on the creation/evolution debate.

Patterns of Synonymous Mutations and the Case for Creation

As noted, many people consider the most compelling evidence for common descent to be the shared genetic features displayed by organisms that naturally cluster together. But if life is the product of a Creator’s handiwork, the shared genetic features could be understood as shared designs deployed by a Creator. In fact, a historical precedent exists for the common design interpretation. Prior to Darwin, biologists viewed shared biological features as manifestations of archetypical designs that existed in the Creator’s mind.

But the common design interpretation requires that the shared features be functional. (Or, that they arise independently in a nonrandom manner.) For those who view life from the framework of the evolutionary paradigm, the shared patterns of synonymous mutations invalidate the common design explanation—because these mutations are considered to be functionally insignificant.

But in the face of mounting evidence for the functional importance of synonymous mutations, this objection to common design has begun to erode. Though many life scientists are quick to dismiss the common design interpretation of biology, advances in molecular biology continue to strengthen this explanation and, with it, the case for a Creator.

Resources

Endnotes
  1. As I discuss in The Cell’s Design, the rules of the genetic code and the nature of the redundancy appear to be designed to minimize errors in translating information from DNA into proteins that would occur due to substitution mutations. This optimization stands as evidence for the work of an intelligent Agent.
  2. JohnCarlo Kristofich et al., “Synonymous Mutations Make Dramatic Contributions to Fitness When Growth Is Limited by Weak-Link Enzyme,” PLoS Genetics 14, no. 8 (August 27, 2018): e1007615, doi:10.1371/journal.pgen.1007615.
  3. Here are a few representative studies that ascribe functional significance to synonymous mutations: Anton A. Komar, Thierry Lesnik, and Claude Reiss, “Synonymous Codon Substitutions Affect Ribosome Traffic and Protein Folding during in vitro Translation,” FEBS Letters 462, no. 3 (November 30, 1999): 387–91, doi:10.1016/S0014-5793(99)01566-5; Chung-Jung Tsai et al., “Synonymous Mutations and Ribosome Stalling Can Lead to Altered Folding Pathways and Distinct Minima,” Journal of Molecular Biology 383, no. 2 (November 7, 2008): 281–91, doi:10.1016/j.jmb.2008.08.012; Florian Buhr et al., “Synonymous Codons Direct Cotranslational Folding toward Different Protein Conformations,” Molecular Cell Biology 61, no. 3 (February 4, 2016): 341–51, doi:10.1016/j.molcel.2016.01.008; Chien-Hung Yu et al., “Codon Usage Influences the Local Rate of Translation Elongation to Regulate Co-translational Protein Folding,” Molecular Cell Biology 59, no. 5 (September 3, 2015): 744–55, doi:10.1016/j.molcel.2015.07.018.
  4. Zubin E. Sauna and Chava Kimchi-Sarfaty,” Understanding the Contribution of Synonymous Mutations to Human Disease,” Nature Reviews Genetics 12 (August 31, 2011): 683–91, doi:10.1038/nrg3051.

Reprinted with permission by the author
Original article at:
https://www.reasons.org/explore/blogs/the-cells-design/read/the-cells-design/2019/03/13/biochemical-synonyms-restate-the-case-for-a-creator

Historical Contingency and the Improbability of Protein Evolution, Part 2 (of 2)

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BY FAZALE RANA – JULY 20, 2016

A few weeks ago, Kathy Emmons of WORD FM in Pittsburg interviewed me about the connection between human evolution and human trafficking. During the interview, she asked me if theological or scientific concerns drove my skepticism about human evolution. My answer is both.

I find it difficult to reconcile the idea of human evolution with passages in the Old and New Testaments that address human origins. But, I also think that there are significant scientific problems confronting the evolutionary paradigm. A recent study by scientists from the Universities of Oregon and Chicago highlights one of those scientific challenges.1

As described in a previous post, these researchers wanted to develop a better understanding of the role that chance historical events play in evolutionary processes. To do this, they reconstructed what they believe to be the evolutionary pathway that led to the emergence of the cortisol-specific glucocorticoid receptor protein, a key component of the vertebrate endocrine system. Based on their reconstruction, it appears that seven amino acid changes transformed the ancestral receptor protein into one that exclusively binds cortisol. They determined that two of the changes were permissive. That is, these changes do not contribute to the binding specificity of the glucocorticoid receptor, but must occur before any of the functional changes took place. Based on their analysis, it appears that the permissive changes were highly improbable, leading the researchers to conclude that historical contingency plays a central role in evolutionary transformations.

According to the researchers:

“If evolutionary history could be replayed from the ancestral starting point, the same kind of permissive substitutions would be unlikely to occur. The transition to GR’s [glucocorticoid receptor’s] present form and function would likely be inaccessible, and different outcomes would almost certainly ensue. Cortisol-specific signaling might evolve by a different mechanism in the GR . . . or the vertebrate endocrine system more generally—would be substantially different.”2

Historical Contingency

The concept of historical contingency is the theme of the late Stephen Jay Gould’s book Wonderful Life.3 According to this idea, the evolutionary process consists of an extended sequence of unpredictable, chance events. To help clarify this concept, Gould used the metaphor of “replaying life’s tape.” If one were to push the rewind button, erase life’s history, and then let the tape run again, the results would be completely different each time.

Gould envisioned historical contingency as primarily resulting from external events (such as climate change or asteroid impacts). But this latest work indicates that the intrinsic complexity of proteins also contributes to historical contingency, because of the necessity and low probability of of permissive amino acid substitutions that support functional changes.

How Widespread Is Historical Contingency?

The question then becomes: How widely applicable is this result? The research team from the Universities of Oregon and Chicago expressed uncertainty regarding this point, but other studies indicate that historical contingency must play a prominent role in molecular evolution.

For example, the long-term evolution experiment conducted by Richard Lenski’s group at Michigan State University demonstrated that the emergence of citrate metabolism in E. coliunder aerobic conditions was historically contingent, predicated on a sequence of chance molecular events. (For more information, see the articles listed under “Resources.”)

Using simulations to monitor the evolution of a protein dubbed argT, researchers from the University of Pennsylvania showed that genetic mutations selected by the evolutionary process are dependent on previous mutations, and over time it becomes increasingly difficult to reverse mutational transformations.4 In other words, an amino acid substitution that occurs in a protein today and is accepted by the evolutionary process would most likely be deleterious if it occurred in the past (because of the central role permissive substitutions play in evolutionary history). Consequently, this mutational change would be selected against by the evolutionary process. One of the researchers involved in this study, Joshua Plotkin, stated,

“There is intrinsically a huge amount of contingency in evolution. Whatever mutations happen to come first set the stage for what other later mutations are permissible. Indeed, history channels evolution down a certain path. Gould’s famous tape of life would be very different if replayed, even more different than Gould might have imagined.”5

A Failed Prediction of the Evolutionary Paradigm

Because the evolutionary process is historically contingent, it seems unlikely that evolutionary processes would lead to identical or nearly identical outcomes. Yet, when viewed from an evolutionary standpoint, it appears as if repeated evolutionary outcomes have been a common occurrence throughout life’s history. This phenomenon—referred to as convergence—is widespread. Evolutionary biologists Simon Conway Morris and George McGhee point out in their respective books Life’s Solution and Convergent Evolution, that identical evolutionary outcomes are a characteristic feature of the biological realm.6 Scientists see these repeated outcomes at the ecological, organismal, biochemical, and genetic levels. In fact, in my book The Cell’s Design, I describe 100 examples of convergence at the biochemical level.

I regard the widespread occurrence of convergence to one of evolution’s failed predictions, and, as I told Kathy Emmons, a justifiable reason to be skeptical of the claim that evolutionary processes can fully explain the history, diversity, and design of life.

In an upcoming blog post, I will further explore the challenge convergence poses for the evolutionary paradigm.

Stay tuned… (or set your tape player to “record.”)

 

Resources

Endnotes

  1. Michael Harms and Joseph Thornton, “Historical Contingency and Its Biophysical Basis in Glucocorticoid Receptor Evolution,” Nature 512 (August 2014): 203–07, doi:10.1038/nature13410.
  2. Ibid., 207.
  3. Stephen Jay Gould, Wonderful Life: The Burgess Shale and the Nature of History (New York: W.W. Norton & Company, 1990).
  4. Premal Shah, David McCandlish, and Joshua Plotkin, “Contingency and Entrenchment in Protein Evolution under Purifying Selection,” Proceedings of the National Academy of Sciences, USA 112 (June 2015): E3226–E3235, doi: 10.1073/pnas.1412933112.
  5. University of Pennsylvania, “Evolution Is Unpredictable and Irreversible, Biologists Show,” ScienceDaily,June 8, 2015, sciencedaily.com/releases/2015/06/150608213032.htm.
  6. Simon Conway Morris, Life’s Solution: Inevitable Humans in a Lonely Universe (New York: Cambridge University Press, 2003); George McGhee, Convergent Evolution: Limited Forms Most Beautiful (Cambridge, MA: MIT Press, 2011).
Reprinted with permission by the author
Original article at:
https://www.reasons.org/explore/blogs/the-cells-design/read/the-cells-design/2016/07/20/historical-contingency-and-the-improbability-of-protein-evolution-part-2-(of-2)

Historical Contingency and the Improbability of Protein Evolution, Part 1 (of 2)

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BY FAZALE RANA – JULY 13, 2016

Can evolutionary processes produce biological innovation?

Critics of the evolutionary paradigm—including me—would say, “No.” However, the reasons for my skepticism differ from many of evolution’s chief detractors. One argument against the evolutionary paradigm that causes me discomfort has to do with the “improbability” of the evolutionary process. For example, one common version of this argument relates to the evolutionary emergence of proteins, with critics asserting that the evolution of novel proteins from preexisting proteins would have been so improbable that it defies an evolutionary explanation. To justify this position, these critics often point to studies such as the one published by scientists from the Universities of Oregon and Chicago that seemingly buttresses their point.1 But does it?

The Evolutionary Origin of a Protein Receptor

This research team hoped to gain insight into the role that chance historical events play in evolutionary processes. Working within the framework of the evolutionary paradigm, they determined what they believe to be the amino acid sequence and structure of the ancestral protein that evolved into the cellular receptor protein that binds the hormone cortisol. They claim to have resurrected an ancient protein they believe existed 450 million years ago, before the cortisol-specific glucocorticoid receptor evolved its specificity for this particular hormone.2

Today, the cortisol-specific glucocorticoid receptor assumes a key role in the endocrine system by regulating development and the stress response. The activity of this protein is mediated by cortisol binding. However, the researchers believe that in the past the ancestral protein was biochemically promiscuous, binding a number of hormones, and only later evolved its specificity for cortisol through amino acid changes mediated by the putative evolutionary process. Based on a reconstruction of the evolutionary pathway, they conclude that seven amino acid changes transformed the ancestral receptor protein into one that exclusively binds cortisol.

The researchers classified the changes into two categories: 1) functional; and 2) permissive. They deemed five of the changes as functional, meaning that these changes contributed to the receptor’s cortisol-binding specificity. They dubbed the other two changes as permissive. These changes do not contribute to the binding specificity of the glucocorticoid receptor, but must occur for the functional changes to take effect. In other words, if the functional changes took place independently of the permissive changes, the resulting hormone receptor would not bind cortisol. The researchers determined that the permissive changes help to stabilize the receptor protein’s structure so that it can tolerate the five functional changes.

Because cortisol binding depends upon the permissive mutations, the researchers reasoned that historical contingency must have played some role in the evolution of the cortisol-specific receptor protein. The permissive mutations must have appeared first, because if they didn’t, the functional changes would not have been selected (again) since they aren’t functional apart from the permissive changes.

The Improbability of Protein Evolution

The question then becomes, “How prominent is contingency in the evolutionary history of the cortisol-specific receptor protein?” To address this point, the investigators synthesized the ancestral receptor protein with the five functional amino acid changes (AP+5). Then, they subjected the AP+5 protein to random amino acid changes to try and determine the number of possible alternate permissive changes that could stabilize the receptor protein in the same way as the historical permissive changes.

They screened about 12,500 random variants of the AP+5 protein. These variants yielded an estimated 1,025 unique single amino acid replacements, 1,802 unique double amino acid replacements, and 825 unique higher order combinations of amino acid substitutions. That is, they examined about 3,650 variants of the AP+5 protein. (The other 8,850 variants were duplicates of the 3,650 variants.) They also engineered 10 additional AP+5 variants using rational design principles. To their surprise, none of the 3,660 variants (3,650 in the screened library, plus the additional 10 engineered double mutants) yielded a functional cortisol-specific receptor that would not disrupt the function of the ancestral protein. (Four of the AP+5 variants displayed cortisol-specific binding, but these four changes destroyed the function of the ancestral protein. From an evolutionary perspective, these alternate permissive substitutions would have been selected against because of their disruptive influence.)

This result indicates that it is highly improbable that the permissive amino acid changes necessary to support the evolution of a cortisol-specific receptor protein could ever occur (with an upper bound of 0.03 percent). The researchers conclude:

“The total frequency is probably far lower…The universe of possible variants containing two or more replacements is very large, so alternative permissive sets may exist; however, these genotypes would require multiple independent substitutions, and the joint probability of such events would be very low because they cannot be acquired deterministically by selection for the derived function.”3

Their probability assessment doesn’t even include the likelihood of the five functional changes occurring after the two permissive changes took place, meaning that the probabilities for the evolution of the cortisol-specific receptor protein from a promiscuous ancestral receptor are even more unlikely.

The Contingency of the Evolutionary Process

As a skeptic of the evolutionary paradigm, it is tempting to point to this study as evidence that evolutionary transformations are so improbable that these processes cannot account for biological innovation. But this would be an unfair conclusion that misrepresents the way evolutionary biologists interpret these results. Instead, these scientists argue that these results tell them something about the evolutionary process: Namely, that historical contingency plays a central role in evolutionary transformations.

The concept of historical contingency is the theme of the late Stephen Jay Gould’s book Wonderful Life.4 According to this idea, the mechanism that drives the evolutionary process consists of an extended sequence of unpredictable, chance events. To help clarify this concept, Gould used the metaphor of “replaying life’s tape.” If one were to push the rewind button, erase life’s history, and then let the tape run again, the results would be completely different each time.

According to the researchers:

“If evolutionary history could be replayed from the ancestral starting point, the same kind of permissive substitutions would be unlikely to occur. The transition to GR’s [glucocorticoid receptor’s] present form and function would likely be inaccessible, and different outcomes would almost certainly ensue. Cortisol-specific signaling might evolve by a different mechanism in the GR—or the vertebrate endocrine system more generally—would be substantially different.”5

A Flawed Argument

In other words, while evolutionary transformations are highly improbable, their unlikelihood cannot be used as a legitimate basis for skepticism about the evolutionary paradigm. To use them in this way would be to make a straw man argument against biological evolution. This probability argument assumes that evolutionary end points are fixed, but evolutionary biologists don’t see them that way at all—because of the historically contingent nature of the process.

Still, there are some legitimate reasons to be skeptical about the capacity of evolutionary mechanisms to account for the design and diversity of life. And one of those reasons is exposed by this study and the historically contingent nature of the evolutionary process.

I will elaborate in my next blog post.

Resources

Endnotes
  1. Michael Harms and Joseph Thornton, “Historical Contingency and Its Biophysical Basis in Glucocorticoid Receptor Evolution,” Nature 512 (August 2014): 203–7.
  2. For a Christian perspective on resurrected ancient proteins, see my article, Fazale Rana, “Resurrected Proteins and the Case for Biological Evolution,” Today’s New Reason to Believe (blog), Reasons to Believe, October 14, 2013, https://www.reasons.org/articles/resurrected-proteins-and-the-case-for-biological-evolution.
  3. Harms and Thornton, “Historical Contingency,” 204.
  4. Stephen Jay Gould, Wonderful Life: The Burgess Shale and the Nature of History (New York: W. W. Norton & Company, 1990).
  5. Harms and Thornton, “Historical Contingency,” 207.
Reprinted with permission by the author
Original article at:
https://www.reasons.org/explore/blogs/the-cells-design/read/the-cells-design/2016/07/13/historical-contingency-and-the-improbability-of-protein-evolution-part-1-(of-2)