During the past few days, Dr. Brian Miller (whose Ph.D. is in physics) has written a series of articles on the origin of life over at Evolution News and Views:
Thermodynamics of the Origin of Life (June 19, 2017)
The Origin of Life, Self-Organization, and Information (June 20, 2017)
Free Energy and the Origin of Life: Natural Engines to the Rescue (June 22, 2017)
Origin of Life and Information — Some Common Myths (June 26, 2017)
Dr. Miller’s aim is to convince his readers that intelligent agency was required to coordinate the steps leading to the origin of life. I think his conclusion may very well be correct, but that doesn’t make his arguments correct. In this post, I plan to subject Dr. Miller’s arguments to scientific scrutiny, in order to determine whether Dr. Miller has made a strong case for Intelligent Design.
While I commend Dr. Miller for his indefatigability, I find it disappointing that his articles recycle several Intelligent Design canards which have been refuted on previous occasions. Dr. Miller also seems to be unaware of recently published online articles which address some of his concerns.
1. Thermodynamics of the Origin of Life
White smokers emitting liquid carbon dioxide at the Champagne vent, Northwest Eifuku volcano, Marianas Trench Marine National Monument. Image courtesy of US NOAA and Wikipedia.
In his first article, Thermodynamics of the Origin of Life, Dr. Miller critiques the popular scientific view that life originated in a “system strongly driven away from equilibrium” (or more technically, a non-equilibrium dissipative system), such as “a pond subjected to intense sunlight or the bottom of the ocean near a hydrothermal vent flooding its surroundings with superheated water and high-energy chemicals.” Dr. Miller argues that this view is fatally flawed, on three counts:
First, no system could be maintained far from equilibrium for more than a limited amount of time. The sun is only out during the day, and superheated water at the bottom of the ocean would eventually migrate away from any hydrothermal vents. Any progress made toward forming a cell would be lost as the system reverted toward equilibrium (lower free energy) and thus away from any state approaching life. Second, the input of raw solar, thermal, or other forms of energy actually increase the entropy of the system, thus moving it in the wrong direction. For instance, the ultraviolet light from the sun or heat from hydrothermal vents would less easily form the complex chemical structures needed for life than break them apart. Finally, in non-equilibrium systems the differences in temperature, concentrations, and other variables act as thermodynamic forces which drive heat transfer, diffusion, and other thermodynamic flows. These flows create microscopic sources of entropy production, again moving the system away from any reduced-entropy state associated with life. In short, the processes occurring in non-equilibrium systems, as in their near-equilibrium counterparts, generally do the opposite of what is actually needed.
Unfortunately for Dr. Miller, none of the foregoing objections is particularly powerful, and most of them are out-of-date. I would also like to note for the record that while the hypothesis that life originated near a hydrothermal vent remains popular among origin-of-life theorists, the notion that this vent was located at “the bottom of the ocean” is now widely rejected. Miller appears to be unaware of this. In fact, as far back as 1988, American chemist Stanley Miller, who became famous when he carried out the Miller-Urey experiment in 1952, had pointed out that long-chain molecules such as RNA and proteins cannot form in water without enzymes to help them. Additionally, leading origin-of-life researchers such as Dr. John Sutherland (of the Laboratory of Molecular Biology in Cambridge, UK) and Dr. Jack Szostak (of Harvard Medical School) have discovered that many of the chemical reactions leading to life depend heavily on the presence of ultraviolet light, which only comes from the sun. This rules out a deep-sea vent scenario. That’s old news. Let us now turn to Dr. Miller’s three objections to the idea of life originating in a non-equilibrium dissipative system.
(a) Could a non-equilibrium be kept away from equilibrium?
Miller’s first objection is that non-equilibrium systems can’t be maintained for very long, which would mean that life would never have had time to form in the first place. However, a recent BBC article by Michael Marshall, titled, The secret of how life on Earth began (October 31, 2016), describes a scenario, proposed by origin-of-life researcher John Sutherland, which would evade the force of this objection. Life, Sutherland believes, may have formed very rapidly:
Sutherland has set out to find a “Goldilocks chemistry”: one that is not so messy that it becomes useless, but also not so simple that it is limited in what it can do. Get the mixture just complicated enough and all the components of life might form at once, then come together.
In other words, four billion years ago there was a pond on the Earth. It sat there for years until the mix of chemicals was just right. Then, perhaps within minutes, the first cell came into existence.
“But how, and where?” readers might ask. One plausible site for this event, put forward by origin-of-life expert Armen Mulkidjanian, is the geothermal ponds found near active volcanoes. Because these ponds would be continually receiving heat from volcanoes, they would not return to equilibrium at night, as Dr. Miller supposes.
Another likely location for the formation of life, proposed by John Sutherland, is a meteorite impact zone. This scenario also circumvents Miller’s first objection, as large-scale meteorite impacts would have melted the Earth’s crust, leading to geothermal activity and a continual supply of hot water. The primordial Earth was pounded by meteorites on a regular basis, and large impacts could have created volcanic ponds where life might have formed:
Sutherland imagines small rivers and streams trickling down the slopes of an impact crater, leaching cyanide-based chemicals from the rocks while ultraviolet radiation pours down from above. Each stream would have a slightly different mix of chemicals, so different reactions would happen and a whole host of organic chemicals would be produced.
Finally the streams would flow into a volcanic pond at the bottom of the crater. It could have been in a pond like this that all the pieces came together and the first protocells formed.
(b) Would an input of energy increase entropy?
What about Miller’s second objection, that the input of energy would increase the entropy of the system, thus making it harder for the complex chemical structures needed for life to form, in the first place?
Here, once again, recent work in the field seems to be pointing to a diametrically opposite conclusion. A recent editorial on non-equilibrium dissipative systems (Nature Nanotechnology 10, 909 (2015)) discusses the pioneering work of Dr. Jeremy England, who maintains that the dissipation of heat in these systems can lead to the self-organization of complex systems, including cells:
The theoretical concepts presented are not new — they have been rigorously reported before in specialized physics literature — but, as England explains, recently there has been a number of theoretical advances that, taken together, might lead towards a more complete understanding of non-equilibrium phenomena. More specifically, the meaning of irreversibility in terms of the amount of work being dissipated as heat as a system moves on a particular trajectory between two states. It turns out, this principle is relatively general, and can be used to explain the self-organization of complex systems such as that observed in nanoscale assemblies, or even in cells.
Dr. England, who is by the way an Orthodox Jew, has derived a generalization of the second law of thermodynamics that holds for systems of particles that are strongly driven by an external energy source, and that can dump heat into a surrounding bath. All living things meet these two criteria. Dr. England has shown that over the course of time, the more likely evolutionary outcomes will tend to be the ones that absorbed and dissipated more energy from the environment’s external energy sources, on the way to getting there. In his own words: “This means clumps of atoms surrounded by a bath at some temperature, like the atmosphere or the ocean, should tend over time to arrange themselves to resonate better and better with the sources of mechanical, electromagnetic or chemical work in their environments.”
There are two mechanisms by which a system might dissipate an increasing amount of energy over time. One such mechanism is self-replication; the other, greater structural self-organization. Natalie Wolchover handily summarizes Dr. England’s reasoning in an article in Quanta magazine, titled, A New Physics Theory of Life (January 22, 2014):
Self-replication (or reproduction, in biological terms), the process that drives the evolution of life on Earth, is one such mechanism by which a system might dissipate an increasing amount of energy over time. As England put it, “A great way of dissipating more is to make more copies of yourself.” In a September paper in the Journal of Chemical Physics, he reported the theoretical minimum amount of dissipation that can occur during the self-replication of RNA molecules and bacterial cells, and showed that it is very close to the actual amounts these systems dissipate when replicating. He also showed that RNA, the nucleic acid that many scientists believe served as the precursor to DNA-based life, is a particularly cheap building material. Once RNA arose, he argues, its “Darwinian takeover” was perhaps not surprising…
Besides self-replication, greater structural organization is another means by which strongly driven systems ramp up their ability to dissipate energy. A plant, for example, is much better at capturing and routing solar energy through itself than an unstructured heap of carbon atoms. Thus, England argues that under certain conditions, matter will spontaneously self-organize. This tendency could account for the internal order of living things and of many inanimate structures as well. “Snowflakes, sand dunes and turbulent vortices all have in common that they are strikingly patterned structures that emerge in many-particle systems driven by some dissipative process,” he said.
Dr. Jeremy England is an MIT physicist. Dr. Miller is also a physicist. I find it puzzling (and more than a little amusing) that Dr. Miller believes that increasing the entropy of a non-equilibrium dissipative system will inhibit the formation of complex chemical structures required for life to exist, whereas Dr. England believes the exact opposite!
(c) Would local variations within non-equilibrium dissipative systems prevent life from forming?
What of Dr. Miller’s third objection, that differences in temperature, concentrations, and other variables arising within a non-equilibrium dissipative system will generate entropy on a microscopic scale, creating disturbances which move the system away from a reduced-entropy state, which is required for life to exist? Dr. David Ruelle, author of a recent Arxiv paper titled, The Origin of Life seen from the point of view of non-equilibrium statistical mechanics (January 29, 2017), appears to hold a contrary view. In his paper, Dr. Ruelle refrains from proposing a specific scenario for the origin of life; rather, his aim, as he puts it, is to describe “a few plausible steps leading to more and more complex states of pre-metabolic systems so that something like life may naturally arise.” Building on the work of Dr. Jeremy England and other authors in the field, Dr. Ruelle contends that “organized metabolism and replication of information” can spontaneously arise from “a liquid bath (water containing various solutes) interacting with some pre-metabolic systems,” where the pre-metabolic systems are defined as “chemical associations which may be carried by particles floating in the liquid, or contained in cracks of a solid boundary of the liquid.” At the end of his paper, Dr. Ruelle discusses what he calls pre-biological systems, emphasizing their ability to remain stable in the face of minor fluctuations, and describing how their complexity can increase over time:
In brief, a pre-biological state is generally indecomposable. This means in particular that the fluctuations in its composition are not large. The prebiological state is also stable under small perturbations, except when those lead to a new metabolic pathway, changing the nature of the state.
We see thus a pre-biological system as a set of components undergoing an organized set of chemical reactions using a limited amount of nutrients in the surrounding fluid. The complexity of the pre-biological system increases as the amount of available nutrients decreases. The system can sustain a limited amount of disturbance. An excessive level of disturbance destroys the organized set of reactions on which the system is based: it dies.
Evidently Dr. Ruelle believes that non-equilibrium dissipative systems are resilient to minor fluctuations, and even capable of undergoing an increase in complexity, whereas Dr. Miller maintains that these fluctuations would prevent the formation of life.
If Dr. Miller believes that Dr. Ruelle is wrong, perhaps he would care to explain why.
2. The Origin of Life, Self-Organization, and Information
The three main structures phospholipids form spontaneously in solution: the liposome (a closed bilayer), the micelle and the bilayer. Image courtesy of Lady of Hats and Wikipedia.
I turn now to Dr. Miller’s second article, The Origin of Life, Self-Organization, and Information. In this article, Dr. Miller argues that there are profound differences between self-organizational order and the cellular order found in living organisms. Non-equilibrium dissipative systems might be able to generate the former kind of order, but not the latter.
The main reason for the differences between self-organizational and cellular order is that the driving tendencies in non-equilibrium systems move in the opposite direction to what is needed for both the origin and maintenance of life. First, all realistic experiments on the genesis of life’s building blocks produce most of the needed molecules in very small concentrations, if at all. And, they are mixed together with contaminants, which would hinder the next stages of cell formation. Nature would have needed to spontaneously concentrate and purify life’s precursors…
Concentration of some of life’s precursors could have taken place in an evaporating pool, but the contamination problem would then become much worse since precursors would be greatly outnumbered by contaminants. Moreover, the next stages of forming a cell would require the concentrated chemicals to dissolve back into some larger body of water, since different precursors would have had to form in different locations with starkly different initial conditions…
In addition, many of life’s building blocks come in both right and left-handed versions, which are mirror opposites. Both forms are produced in all realistic experiments in equal proportions, but life can only use one of them: in today’s life, left-handed amino acids and right-handed sugars. The origin of life would have required one form to become increasingly dominant, but nature would drive a mixture of the two forms toward equal percentages, the opposite direction.
(a) Why origin-of-life theorists are no longer obsessed with purity
Dr. Miller’s contention that contaminants would hinder the formation of living organisms has been abandoned by modern origin-of-life researchers, as BBC journalist Michael Marshall reports in his 2016 article, The secret of how life on Earth began. After describing how researcher John Sutherland was able to successfully assemble a nucleotide using a messy solution that contained a contaminant (phosphate) at the outset, leading Sutherland to hypothesize that for life to originate, there has to be “an optimum level of mess” (neither too much nor too little), Marshall goes on to discuss the pioneering experiments of another origin-of-life researcher, Jack Szostak, whose work has led him to espouse the same conclusion as Sutherland:
Szostak now suspects that most attempts to make the molecules of life, and to assemble them into living cells, have failed for the same reason: the experiments were too clean.
The scientists used the handful of chemicals they were interested in, and left out all the other ones that were probably present on the early Earth. But Sutherland’s work shows that, by adding a few more chemicals to the mix, more complex phenomena can be created.
Szostak experienced this for himself in 2005, when he was trying to get his protocells to host an RNA enzyme. The enzyme needed magnesium, which destroyed the protocells’ membranes.
The solution was a surprising one. Instead of making the vesicles out of one pure fatty acid, they made them from a mixture of two. These new, impure vesicles could cope with the magnesium – and that meant they could play host to working RNA enzymes.
What’s more, Szostak says the first genes might also have embraced messiness.
Modern organisms use pure DNA to carry their genes, but pure DNA probably did not exist at first. There would have been a mixture of RNA nucleotides and DNA nucleotides.
In 2012 Szostak showed that such a mixture could assemble into “mosaic” molecules that looked and behaved pretty much like pure RNA. These jumbled RNA/DNA chains could even fold up neatly.
This suggested that it did not matter if the first organisms could not make pure RNA, or pure DNA…
(b) Getting it together: how the first cell may have formed
Dr. Miller also argues that even if the components of life were able to form in separate little pools, the problem of how they came to be integrated into a living cell would still remain. In recent years, Dr. John Sutherland has done some serious work on this problem. Sutherland describes his own preferred origin-of-life scenario in considerable detail in a paper titled, The Origin of Life — Out of the Blue (Angewandte Chemie, International Edition, 2016, 55, 104 – 121.
Several years ago, we realised that … polarisation of the field was severely hindering progress, and we planned a more holistic approach. We set out to use experimental chemistry to address two questions, the previously assumed answers to which had led to the polarisation of the field: “Are completely different chemistries needed to make the various subsystems?” [and] “Would these chemistries be compatible with each other?”…
With twelve amino acids, two ribonucleotides and the hydrophilic moiety of lipids synthesised by common chemistry, we feel that we have gone a good way to answering the first of the questions we posed at the outset. “Are completely different chemistries needed to make the various subsystems?” — we would argue no! We need to find ways of making the purine ribonucleotides, but hydrogen cyanide 1 is already strongly implicated as a starting material. We also need to find ways of making the hydrophobic chains of lipids, and maybe a few other amino acids, but there is hope in reductive homologation chemistry or what we have called “cyanosulfidic protometabolism.” …
The answer to the second question — “Would these chemistries be compatible with each other?” — is a bit more vague (thus far). The chemistries associated with the different subsystems are variations on a theme, but to operate most efficiently some sort of separation would seem to be needed. Because a late stage of our scenario has small streams or rivulets flowing over ground sequentially leaching salts and other compounds as they are encountered (Figure 17), it provides a very simple way in which variants of the chemistry could play out separately before all the products became mixed.
Separate streams might encounter salts and other compounds in different orders and be exposed to solar radiation differently. Furthermore streams might dry out and the residues become heated through geothermal activity before fresh inflow of water. If streams with different flow chemistry histories then merged, convergent synthesis might occur at the confluence and downstream thereof, or products might simply mix. It would be most plausible if only a few streams were necessary for the various strands of the chemistry to operate efficiently before merger. Our current working model divides the reaction network up such that the following groups of building blocks would be made separately: ribonucleotides; alanine, threonine, serine and glycine; glycerol phosphates, valine and leucine; aspartic acid, asparagine, glutamic acid and glutamine; and arginine and proline. Because the homologation of all intermediates uses hydrogen cyanide (1), products of reductive homologation of (1) — especially glycine — could be omnipresent.
Since then, Sutherland has written another paper, titled, Opinion: Studies on the origin of life — the end of the beginning (Nature Reviews Chemistry 1, article number: 0012 (2017), doi:10.1038/s41570-016-0012), in which he further develops his scenario.
(c) How did life come to be left-handed?
Two enantiomers [mirror images] of a generic amino acid which is chiral [left- or right-handed]. Image courtesy of Wikipedia.
The left-handedness of amino acids in living things, coupled with the fact that that organisms contain only right-handed nucleotides, has puzzled origin-of-life theorists since the time of Pasteur. Does this rule put a natural origin for living things, as Dr. Miller thinks? It is interesting to note that Pasteur himself was wary of drawing this conclusion, according to a biography written by his grandson, and he even wrote: “I do not judge it impossible.” (René Dubos, Louis Pasteur: Free Lance of Science, Da Capo Press, Inc., 1950. p 396.)
Pasteur’s caution turns out to have been justified. According to a 2015 report by Claudia Lutz in Phys.org titled, Straight up, with a twist: New model derives homochirality from basic life requirements, scientists at the University of Illinois have recently come up with a simple model which explains the chirality found in living organisms in terms of just two basic properties: self-replication and disequilibrium.
The Illinois team wanted to develop a … model, … based on only the most basic properties of life: self-replication and disequilibrium. They showed that with only these minimal requirements, homochirality appears when self-replication is efficient enough.
The model … takes into account the chance events involving individual molecules — which chiral self-replicator happens to find its next substrate first. The detailed statistics built into the model reveal that if self-replication is occurring efficiently enough, this incidental advantage can grow into dominance of one chirality over the other.
The work leads to a key conclusion: since homochirality depends only on the basic principles of life, it is expected to appear wherever life emerges, regardless of the surrounding conditions.
More recent work has provided a detailed picture of how life’s amino acids became left-handed. In 2016, Rowena Ball and John Brindley proposed that since hydrogen peroxide is the smallest, simplest molecule to exist as a pair of non-superimposable mirror images, or enantiomers, its interactions with ribonucelic acids may have led to amplification of D-ribonucleic acids and extinction of L-ribonucleic acids. Hydrogen peroxide was produced on the ancient Earth, more than 3.8 billion years ago, around the time that life emerged. Ball explains how this favored the emergence of right-handed nucleotide chains, in a recent article in Phys.org:
It is thought that a small excess of L-amino acids was “rained” onto the ancient Earth by meteorite bombardment, and scientists have found that a small excess of L-amino acids can catalyse formation of small excesses of D-nucleotide precursors. This, we proposed, led to a marginal excess of D-polynucleotides over L-polynucleotides, and a bias to D-chains of longer mean length than L-chains in the RNA world.
In the primordial soup, local excesses of one or other hydrogen peroxide enantiomer would have occurred. Specific interactions with polynucleotides destabilise the shorter L-chains more than the longer, more robust, D-chains. With a greater fraction of L-chains over D-chains destabilised, hydrogen peroxide can then “go in for the kill”, with one enantiomer (let us say M) preferentially oxidising L-chains.
Overall, this process works in favour of increasing the fraction and average length of D-chains at the expense of L-species.
An outdated argument relating to proteins
In his article, Dr. Miller puts forward an argument for proteins having been intelligently designed, which unfortunately rests on faulty premises:
Proteins eventually break down, and they cannot self-replicate. Additional machinery was also needed to constantly produce new protein replacements. Also, the proteins’ sequence information had to have been stored in DNA using some genetic code, where each amino acid was represented by a series of three nucleotides know as a codon in the same way English letters are represented in Morse Code by dots and dashes. However, no identifiable physical connection exists between individual amino acids and their respective codons. In particular, no amino acid (e.g., valine) is much more strongly attracted to any particular codon (e.g., GTT) than to any other. Without such a physical connection, no purely materialistic process could plausibly explain how amino acid sequences were encoded into DNA. Therefore, the same information in proteins and in DNA must have been encoded separately.
The problem with this argument is that scientists have known for decades that its key premise is false. Dennis Venema (Professor of Biology at Trinity Western University in Langley, British Columbia) explains why, in a Biologos article titled, Biological Information and Intelligent Design: Abiogenesis and the origins of the genetic code (August 25, 2016):
Several amino acids do in fact directly bind to their codon (or in some cases, their anticodon), and the evidence for this has been known since the late 1980s in some cases. Our current understanding is that this applies only to a subset of the 20 amino acids found in present-day proteins.
In Venema’s view, this finding lends support to a particular hypothesis about the origin of the genetic code, known as the direct templating hypothesis, which proposes that “the tRNA system is a later addition to a system that originally used direct chemical interactions between amino acids and codons.” Venema continues: “In this model, then, the original code used a subset of amino acids in the current code, and assembled proteins directly on mRNA molecules without tRNAs present. Later, tRNAs would be added to the system, allowing for other amino acids—amino acids that cannot directly bind mRNA — to be added to the code.” The model also makes a specific prediction: if it is correct, then “amino acids would directly bind to their codons on mRNA, and then be joined together by a ribozyme (the ancestor of the present-day ribosome).”
Venema concludes:
The fact that several amino acids do in fact bind their codons or anticodons is strong evidence that at least part of the code was formed through chemical interactions — and, contra [ID advocate Stephen] Meyer, is not an arbitrary code. The code we have — or at least for those amino acids for which direct binding was possible — was indeed a chemically favored code. And if it was chemically favored, then it is quite likely that it had a chemical origin, even if we do not yet understand all the details of how it came to be.
I will let readers draw their own conclusions as to who has the better of the argument here: Venema or Miller.
3. Free Energy and the Origin of Life: Natural Engines to the Rescue
Photograph of American scientist Josiah Willard Gibbs (1839-1903), discoverer of Gibbs free energy, taken about 1895. Image courtesy of Wikipedia.
In his third article, Free Energy and the Origin of Life: Natural Engines to the Rescue, Dr. Miller argues that the emergence of life would have required chemicals to move from a state of high entropy and low free energy to one of low entropy and high free energy. (Gibbs free energy can be defined as “a thermodynamic potential that can be used to calculate the maximum of reversible work that may be performed by a thermodynamic system at a constant temperature and pressure.”) However, spontaneous natural processes always tend towards lower free energy. An external source of energy doesn’t help matters, either, as it increases entropy. Miller concludes that life’s formation was intelligently directed:
Now, I will address attempts to overcome the free-energy barriers through the use of natural engines. To summarize, a fundamental hurdle facing all origin-of-life theories is the fact that the first cell must have had a free energy far greater than its chemical precursors. And spontaneous processes always move from higher free energy to lower free energy. More specifically, the origin of life required basic chemicals to coalesce into a state of both lower entropy and higher energy, and no such transitions ever occur without outside help in any situation, even at the microscopic level.
Attempted solutions involving external energy sources fail since the input of raw energy actually increases the entropy of the system, moving it in the wrong direction. This challenge also applies to all appeals to self-replicating molecules, auto-catalytic chemical systems, and self-organization. Since all of these processes proceed spontaneously, they all move from higher to lower free energy, much like rocks rolling down a mountain. However, life resides at the top of the mountain. The only possible solutions must assume the existence of machinery that processes energy and directs it toward performing the required work to properly organize and maintain the first cell.
But as we saw above, Dr. Jeremy England maintains that increasing the entropy of a non-equilibrium dissipative system can promote the formation of complex chemical structures required for life to exist. Miller’s claim that external energy sources invariably increase the entropy of the system is correct if we consider the system as a whole, including the bath into which non-equilibrium dissipative systems can dump their heat. Internally, however, self-organization can reduce entropy- a fact which undermines Miller’s attempt to demonstrate the impossibility of abiogenesis.
4. Origin of Life and Information — Some Common Myths
A game of English-language Scrabble in progress. Image courtesy of Wikipedia.
In his final installment, Origin of Life and Information — Some Common Myths, Dr. Miller takes aim at the view that a reduction in entropy is sufficient to account for the origin of biological information. Miller puts forward three arguments which he believes demonstrate the absurdity of this idea.
(a) Could a reduction in entropy generate functional information?
A bowl of alphabet soup nearly full, and nearly empty, spelling “THE END” in the latter case. Image courtesy of strawberryblues and Wikipedia.
Let’s look at Miller’s first argument, that a reduction in entropy could never account for the highly specific sequencing of amino acids in proteins, or nucleotides in DNA:
A common attempt to overcome the need for information in the first cell is to equate information to a reduction in entropy, often referred to as the production of “negative entropy” or N-entropy. … However, entropy is not equivalent to the information in cells, since the latter represents functional information. To illustrate the difference, imagine entering the kitchen and seeing a bowl of alphabet soup with several letters arranged in the middle as follows:
REST TODAY AND DRINK PLENTY OF FLUIDS
I HOPE YOU FEEL BETTER SOON
You would immediately realize that some intelligence, probably your mother, arranged the letters for a purpose. Their sequence could not possibly be explained by the physics of boiling water or the chemistry of the pasta.
… You would immediately recognize that a reduction in thermal entropy has no physical connection to the specific ordering of letters in a meaningful message. The same principle holds true in relation to the origin of life for the required sequencing of amino acids in proteins or nucleotides in DNA.
This, I have to say, is a fallacious argument, which I refuted in my online review of Dr. Douglas Axe’s recently published book, Undeniable. Dr. Miller, like Dr. Axe, is confusing functional information (which is found in living things) with the semantic information found in a message written with the letters of the alphabet, such as “REST TODAY AND DRINK PLENTY OF FLUIDS.” In fact, functional information is much easier to generate than semantic information, because it doesn’t have to form words, conform to the rules of syntax, or make sense at the semantic level:
The concepts of meaning and function are quite different, for reasons I shall now explain.
In order for an accidentally generated string of letters to convey a meaningful message, it needs to satisfy three very stringent conditions, each more difficult than the last: first, the letters need to be arranged into meaningful words; second, the sequence of words has to conform to the rules of syntax; and finally, the sequence of words has to make sense at the semantic level: in other words, it needs to express a meaningful proposition. For a string of letters generated at random to meet all of these conditions would indeed be fantastically improbable. But here’s the thing: living things don’t need to satisfy any of these conditions... The sequence of amino acids in a protein needs to do just one thing: it needs to fold up into a shape that can perform a biologically useful task. And that’s it. Generating something useful by chance – especially something with enough useful functions to be called alive – is a pretty tall order, but because living things lack the extra dimensions of richness found in messages that carry a semantic meaning, they’re going to be a lot easier to generate by chance than (say) instruction manuals or cook books… In practical terms, that means that given enough time, life just might arise.
Let me be clear: I am not trying to argue that a reduction in entropy is sufficient to account for the origin of biological information. That strikes me as highly unlikely. What I am arguing, however, is that appeals to messages written in text are utterly irrelevant to the question of how biological information arose. I might also add that most origin-of-life theorists don’t believe that the first living things contained highly specific sequences of “amino acids in proteins or nucleotides in DNA,” as Miller apparently thinks, because they probably lacked both proteins and DNA, if the RNA World hypothesis (discussed below) is correct. Miller is attacking a straw man.
(b) Can fixed rules account for the amino acid sequencing in proteins?
Dr. Miller’s second argument is that fixed rules, such as those governing non-linear dynamics processes, would be unable to generate the arbitrary sequences of amino acids found in proteins. These sequences perform useful biological functions, but are statistically random:
A related error is the claim that biological information could have come about by some complex systems or non-linear dynamics processes. The problem is that all such processes are driven by physical laws or fixed rules. And, any medium capable of containing information (e.g., Scrabble tiles lined up on a board) cannot constrain in any way the arrangement of the associated symbols/letters. For instance, to type a message on a computer, one must be free to enter any letters in any order. If every time one typed an “a” the computer automatically generated a “b,” the computer could no longer contain the information required to create meaningful sentences. In the same way, amino acid sequences in the first cell could only form functional proteins if they were free to take on any order…
…To reiterate, no natural process could have directed the amino acid sequencing in the first cell without destroying the chains’ capacity to contain the required information for proper protein folding. Therefore, the sequences could never be explained by any natural process but only by the intended goal of forming the needed proteins for the cell’s operations (i.e., teleologically).
Dr. Miller has a valid point here: it is extremely unlikely that fixed rules, by themselves, can explain the origin of biological information. Unfortunately, he spoils his case by likening the information in a protein to a string of text. As we have seen, the metaphor is a flawed one, on three counts. Proteins contain functional information, not semantic information.
Dr. Miller also makes an illicit inference from the statement that “no natural process could have directed the amino acid sequencing in the first cell” to the conclusion that “the sequences could never be explained by any natural process,” but only by a teleological process of Intelligent Design. This inference is unwarranted on two counts. First, it assumes that the only kind of natural explanation for the amino acid sequences in proteins would have to be some set of fixed rules (or laws) directing their sequence, which overlooks the possibility that functional sequences may have arisen by chance. (At this point, Intelligent Design advocates will be sure to cite Dr. Douglas Axe’s estimate that only 1 in 10^77 sequences of 150 amino acids are capable of folding up and performing some useful biological function, but this figure is a myth.)
Second, teleology may be either intrinsic (e.g. hearts are of benefit to animals, by virtue of the fact that they pump blood around the body) or extrinsic (e.g. a machine which is designed for the benefit of its maker), or both. Even if one could show that a teleological process was required to explain the origin of proteins, it still needs to be shown that this process was designed by an external Intelligence.
(c) Can stereochemical affinity account for the origin of the genetic code?
Origin-of-life researcher Eugene Koonin in May 2013. Koonin is a Russian-American biologist and Senior Investigator at the National Center for Biotechnology Information (NCBI). Image courtesy of Konrad Foerstner and Wikipedia.
Dr. Miller then goes on to criticize the stereochemical affinity hypothesis for the origin of the genetic code, citing the work of Dr. Eugene Koonin:
A third error relates to attempts to explain the genetic code in the first cell by a stereochemical affinity between amino acids and their corresponding codons. According to this model, naturally occurring chemical processes formed the basis for the connection between amino acids and their related codons (nucleotide triplets). Much of the key research promoting this theory was conducted by biochemist Michael Yarus. He also devised theories on how this early stereochemical era could have evolved into the modern translation system using ribosomes, tRNAs, and supporting enzymes. His research and theories are clever, but his conclusions face numerous challenges.
…For instance, Andrew Ellington’s team questioned whether the correlations in these studies were statistically significant, and they argued that his theories for the development of the modern translation system were untenable. Similarly, Eugene Koonin found that the claimed affinities were weak at best and generally unconvincing. He argued instead that the code started as a “frozen accident” undirected by any chemical properties of its physical components.
I should point out here that some of the articles which Miller links to here are rather old. For example, the article by Andrew Ellington’s team questioning the statistical significance of the correlations identified by Yarus dates back to 2000, while Koonin’s critique dates back to 2008. This is significant, as Yarus et al. published an article in 2009 presenting some of their strongest statistical evidence for the stereochemical model they were proposing:
Using recent sequences for 337 independent binding sites directed to 8 amino acids and containing 18,551 nucleotides in all, we show a highly robust connection between amino acids and cognate coding triplets within their RNA binding sites. The apparent probability (P) that cognate triplets around these sites are unrelated to binding sites is [about] 5.3 x 10-45 for codons overall, and P [is about] 2.1 x 10-46 for cognate anticodons. Therefore, some triplets are unequivocally localized near their present amino acids. Accordingly, there was likely a stereochemical era during evolution of the genetic code, relying on chemical interactions between amino acids and the tertiary structures of RNA binding sites. (Michael Yarus, Jeremy Joseph Widmann and Rob Knight, “RNA–Amino Acid Binding: A Stereochemical Era for the Genetic Code,” in Journal of Molecular Evolution, November 2009; 69(5):406-29, DOI 10.1007/s00239-009-9270-1.)
Dr. Miller also neglects to mention that while Dr. Eugene Koonin did indeed critique Yarus’ claims in the more recent 2017 article he linked to, Koonin actually proposed his own variant of the stereochemical model for the origin of the genetic code:
The conclusion that the mRNA decoding in the early translation system was performed by RNA molecules, conceivably, evolutionary precursors of modern tRNAs (proto-tRNAs) [89], implies a stereochemical model of code origin and evolution, but one that differs from the traditional models of this type in an important way (Figure 2). Under this model, the proto-RNA-amino acid interactions that defined the specificity of translation would not involve the anticodon (let alone codon) that therefore could be chosen arbitrarily and fixed through frozen accident. Instead, following the reasoning outlined previously [90], the amino acids would be recognized by unique pockets in the tertiary structure of the proto-tRNAs. The clustering of codons for related amino acids naturally follows from code expansion by duplication of the proto-tRNAs; the molecules resulting from such duplications obviously would be structurally similar and accordingly would bind similar amino acids, resulting in error minimization, in accord with Crick’s proposal (Figure 2).
Apparently, the reason why Koonin considers that “attempts to decipher the primordial stereochemical code by comparative analysis of modern translation system components are largely futile” is that “[o]nce the amino acid specificity determinants shifted from the proto-tRNAs to the aaRS, the amino acid-binding pockets in the (proto) tRNAs deteriorated such that modern tRNAs showed no consistent affinity to the cognate amino acids.” Koonin proposes that “experiments on in vitro evolution of specific aminoacylating ribozymes that can be evolved quite easily and themselves seem to recapitulate a key aspect of the primordial translation system” might help scientists to reconstruct the original code, at some future date.
Although (as Dr. Miller correctly notes) Koonin personally favors the frozen accident theory for the origin of the genetic code, he irenically proposes that “stereochemistry, biochemical coevolution, and selection for error minimization could have contributed synergistically at different stages of the evolution of the code [43] — along with frozen accident.”
Positive evidence against the design of the genetic code
But there is much more to Koonin’s article. Koonin presents damning evidence against the hypothesis that the standard genetic code (or SGC) was designed, in his article. The problem is that despite the SGC’s impressive ability to keep the number of mutational and translational errors very low, there are lots of other genetic codes which are even better:
Extensive quantitative analyses that employed cost functions differently derived from physico-chemical properties of amino acids have shown that the code is indeed highly resilient, with the probability to pick an equally robust random code being on the order of 10−7–10−8 [14,15,61,62,63,64,65,66,67,68]. Obviously, however, among the ~1084 possible random codes, there is a huge number with a higher degree of error minimization than the SGC [standard genetic code – VJT]. Furthermore, the SGC is not a local peak on the code fitness landscape because certain local rearrangements can increase the level of error minimization; quantitatively, the SGC is positioned roughly halfway from an average random code to the summit of the corresponding local peak [15] (Figure 1).
Let’s do the math. There are about 1084 possible genetic codes. The one used by living things is in the top 1 in 100 million (or 1 in 108). That means that there are 1076 possible genetic codes that are better than it. To make matters worse, it’s not even the best code in its local neighborhood. It’s not “on top of a hill,” as it were. It’s about half-way up the hill. Now ask yourself: if the genetic code were intelligently designed, is this a result that one would expect?
It is disappointing that Dr. Miller fails to appreciate the significance of this evidence against design, presented by Koonin. Sadly, he never even mentions it in his article.
The RNA World – fatally flawed?
A comparison of RNA (left) with DNA (right), showing the helices and nucleobases each employs. Image courtesy of Access Excellence and Wikipedia.
Finally, Dr. Miller concludes with a number of critical remarks about the RNA world hypothesis. Before we proceed further, a definition of the hypothesis might be in order:
All RNA World hypotheses include three basic assumptions: (1) At some time in the evolution of life, genetic continuity was assured by the replication of RNA; (2) Watson-Crick base-pairing was the key to replication; (3) genetically encoded proteins were not involved as catalysts. RNA World hypotheses differ in what they assume about life that may have preceded the RNA World, about the metabolic complexity of the RNA World, and about the role of small-molecule cofactors, possibly including peptides, in the chemistry of the RNA World.
(Michael P. Robertson and Gerald F. Joyce, The Origins of the RNA World, Cold Spring Harbor Perspectives in Biology, May 2012; 4(5): a003608.)
In the article cited above, Robertson and Joyce summarize the evidence for the RNA World:
There is now strong evidence indicating that an RNA World did indeed exist on the early Earth. The smoking gun is seen in the structure of the contemporary ribosome (Ban et al. 2000; Wimberly et al. 2000; Yusupov et al. 2001). The active site for peptide-bond formation lies deep within a central core of RNA, whereas proteins decorate the outside of this RNA core and insert narrow fingers into it. No amino acid side chain comes within 18 Å of the active site (Nissen et al. 2000). Clearly, the ribosome is a ribozyme (Steitz and Moore 2003), and it is hard to avoid the conclusion that, as suggested by Crick, “the primitive ribosome could have been made entirely of RNA” (1968).
A stronger version of the RNA World hypothesis is that life on Earth began with RNA. In the article cited above, Robertson and Joyce are very frank about the difficulties attending this hypothesis, even referring to it as “The Prebiotic Chemist’s Nightmare.” Despite their sympathies for this hypothesis, the authors suggest that it may be fruitful to consider “the alternative possibility that RNA was preceded by some other replicating, evolving molecule, just as DNA and proteins were preceded by RNA.”
The RNA World hypothesis has its scientific advocates and critics. In a recent article in Biology Direct, Harold S. Bernhardt describes it as “the worst theory of the early evolution of life (except for all the others),” in a humorous adaptation of Sir Winston Churchill’s famous comment on democracy. Referee Eugene Koonin agrees, noting that “no one has achieved bona fide self-replication of RNA which is the cornerstone of the RNA World,” but adding that “there is a lot going for the RNA World … whereas the other hypotheses on the origin of life are outright helpless.” Koonin continues: “As Bernhardt rightly points out, it is not certain that RNA was the first replicator but it does seem certain that it was the first ‘good’ replicator.”
In 2009, Gerald Joyce and Tracey Lincoln of the Scripps Research Institute in La Jolla, California, managed to create an RNA enzyme that replicates itself indirectly, by joining together two short pieces of RNA to create a second enzyme, which then joins together another two RNA pieces to recreate the original enzyme. Although the cycle was capable of being continued indefinitely, given an input of suitable raw materials, the enzymes were only able to do their job if they were given the correct RNA strands, which Joyce and Lincoln had to synthesize.
The RNA world hypothesis received a further boost in March 2015, when NASA scientists announced for the first time that, using the starting chemical pyrimidine, which is found in meteorites, they had managed to recreate three key components of DNA and RNA: uracil, cytosine and thymine. The scientists used an ice sample containing pyrimidine exposed to ultraviolet radiation under space-like conditions, in order to produce these essential ingredients of life. “We have demonstrated for the first time that we can make uracil, cytosine, and thymine, all three components of RNA and DNA, non-biologically in a laboratory under conditions found in space,” said Michel Nuevo, research scientist at NASA’s Ames Research Center, Moffett Field, California. “We are showing that these laboratory processes, which simulate conditions in outer space, can make several fundamental building blocks used by living organisms on Earth.”
As if that were not enough, more good news for the hypothesis emerged in 2016. RNA is composed of four different chemical building blocks: adenine (A), guanine (G), cytosine (C), and uracil (U). Back in 2009, a team of researchers led by John Sutherland showed a plausible series of chemical steps which might have given rise to cytosine and uracil, which are also known as pyrimidines, on the primordial Earth.However, Sutherland’s team wasn’t able to explain the origin of RNA’s purine building blocks, adenine and guanine. At last, a team of chemists led by Thomas Carell, at Ludwig Maximilian University of Munich in Germany, has filled in this gap in scientists’ knowledge. They’ve found a synthetic route for making purines. To be sure, problems remain, as reporter Robert Service notes in a recent article in Science magazine (‘RNA world’ inches closer to explaining origins of life, May 12, 2016):
…Steven Benner, a chemist and origin of life expert at the Foundation for Applied Molecular Evolution in Alachua, Florida… agrees that the newly suggested purine synthesis is a “major step forward” for the field. But even if it’s correct, he says, the chemical conditions that gave rise to the purines still don’t match those that Sutherland’s group suggests may have led to the pyrimidines. So just how As, Gs, Cs, and Us would have ended up together isn’t yet clear. And even if all the RNA bases were in the same place at the same time, it’s still not obvious what drove the bases to link up to form full-fledged RNAs, Benner says.
I conclude that whatever difficulties attend the RNA World hypothesis, they are not fatal ones. Miller’s case for the intelligent design of life is far from closed.
Conclusion
James M. Tour is a synthetic organic chemist, specializing in nanotechnology. Dr. Tour is the T. T. and W. F. Chao Professor of Chemistry, Professor of Materials Science and NanoEngineering, and Professor of Computer Science at Rice University in Houston, Texas. Image courtesy of Wikipedia.
At the beginning of this post, I invited my readers to consider the question of whether Dr. Miller has made a strong scientific case for Intelligent Design. Now, I would happily grant that he has highlighted a number of difficulties for any naturalistic theory of the origin of life. But I believe I have shown that Dr. Miller’s positive case for Intelligent Design consists largely of trying to put a full stop where science leaves a comma. Dr. Miller seems to have ignored recent developments in the field of origin-of-life research, which remove at least some of the difficulties he alludes to in his articles. I think an unbiased reader would have to conclude that Miller has failed to demonstrate, to even a high degree of probability, the need for a Designer of life.
I’d like to finish with two quotes from an online essay (Origin of Life, Intelligent Design, Evolution, Creation and Faith) by Dr. James Tour, a very fair-minded chemist who has written a lot about the origin of life:
I have been labeled as an Intelligent Design (sometimes called “ID”) proponent. I am not. I do not know how to use science to prove intelligent design although some others might. I am sympathetic to the arguments and I find some of them intriguing, but I prefer to be free of that intelligent design label. As a modern-day scientist, I do not know how to prove intelligent design using my most sophisticated analytical tools— the canonical tools are, by their own admission, inadequate to answer the intelligent design question. I cannot lay the issue at the doorstep of a benevolent creator or even an impersonal intelligent designer. All I can presently say is that my chemical tools do not permit my assessment of intelligent design.
and
Those who think scientists understand the issues of prebiotic chemistry are wholly misinformed. Nobody understands them. Maybe one day we will. But that day is far from today.
Amen to both.
Yeah, “statistical genome” was new to me. That’s an important part of the puzzle to know about. And I do appreciate having someone like Rumraket here to pass along the information.
Mung
“Not only that, but it’s likewise obvious that his claim is theological, not scientific.”
Are you claiming that the Designer has to be God? If not, then the claim is not theological.
Well, slow down a second now Walto. Just because he said a lot of words, it doesn’t mean he is solving the tough problems. The fundamental question is, did a random code, one that was completely undesigned, get random mutations, which then made it less likely to get random mutations, and then because it got these random mutations, that caused a reproductive benefit, which resulted in entire populations having genomes which can’t get random mutations.
The second question is, would other codes do better than this at producing life (He hasn’t even come close to answering this one. In fact what he seems to be saying in regards to this second question, is that the code is miraculous in its ability to do exactly what it needs to do-surprise surprise!. I thought he was complaining other codes would do so much better. Huh? How is this demonstrating that claim. Its not, so on to the first.)
Now did Rumraket show this to be the case-not so fast. Rumraket has a tendency to proclaim that just because he said something, he must have proven a claim. Try to keep your skeptic hat on for just a second. This may take a while. I guarantee if any theist would throw this much stuff against the wall, and claim it says what they claim, they would be accused of posting gish-gallup. And this is exactly what I would accuse Rumraket of.
But I will respond to some of these points-because the articles he is linking to, ARE MOST CERTAINLY not supporting a notion that the genome is so set -by random mutations to prevent “deleterious” mutations (when earlier forms of the genome allowed more deleterious mutations in his words), but rather that there are many redundancies, and further more that these redundancies are CIRCUMVENTED in order to make the genome MORE plastic in some bacteria when it is needed to fight hosts defense systems! It seems pretty unbelievable (I guess it shouldn’t be) that he is using THIS as an example of how mutations make the genome LESS susceptible to alteration-when that is exactly the opposite of what this study is talking about.
It says it right there in the quote for crying out loud!:
In other words, it appears to be saying that they EVOLVED the ability to get MORE mutations, not less, when needed to fight more immune defense systems! More randomness just so happening to work out perfectly, gee.
Wobble, wobble wobble…
If all Rumraket really wanted to say was, the genome is very robust when it needs to be, and also completely malleable and plastic at other times when needed, WHO IS HE ARGUING WITH?? Because I sure don’t see how anyone on our side with have a problem with this argument.
I am just trying to figure out how this is helping his cause, THAT OTHER GENETIC CODES WOULD WORK SO MUCH BETTER at preventing deleterious (all!) mutations. So how would other genetic codes do better than this?
Bullshit.
If Rumraket wants to make my case for me, that the genome is amazingly able to perform exactly the tasks it needs to in order to sustain life, a sure sign that it is NOT a random code, I guess I should thank him.
It’s a term first (I think) coined by Carl Woese in 1965 in a publication on one of the very first hypotheses for the origin of the genetic code.
[ C R Woese. On the evolution of the genetic code. Proc Natl Acad Sci U S A. 1965 Dec; 54(6): 1546–1552. PMCID: PMC300511]
“Two important consequences stem immediately from this concept of error-ridden translation in the primitive cell: (1) since perfect translations of a gene are neglible (and thus no two proteins in the cell are identical), the proteins produced by any given gene will have to be what we shall call ”statistical proteins” – i.e., to each gene there corresponds a group of proteins whose primary structures are related to some theoretical average primary structure, which in turn characterizes the gene; (2) it would be relatively easy to alter actual codon assignments, since this would in many cases have little or no deleterious effect on the already rather chaotic situation existing in the primitive cell.”
That paper is well worth a read btw. So is his paper from 2002 on the origin of life:
[Woese CR. On the evolution of cells. Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8742-7. Epub 2002 Jun 19. DOI: 10.1073/pnas.132266999]
Rumraket,
Carl Woese the Darwinian skeptic? That Woese?
More stupid misrepresentations from you, gee.
But hey, still waiting for an explanation on why all this randomness is incompatible with ID. You keep getting your knickers in a bunch over “randomness” doing the job of the Designer, but if the Designer had some transcendent superpowers that somehow enabled her to produce all the life diversity and it’s code by means of random mutations and natural selection (that you keep forgetting about), who are you to question her creation? who are you to doubt her omnipotence, you poor ignorant, insignificant speck?
Yes, that one. The one that knows there’s more to evolution than just natural selection.
NO, they did not evolve that ability. Because, as Rumraket already noted, the genetic code doesn’t affect the mutation rate. The paper discusses lowered translation fidelity which has nothing to do with DNA replication.
you seem to be struggling with the difference between gene expression and genomic sequence. So, just to clarify: if you say that the genome is robust or plastic, do you mean the DNA sequence or the expression of it?
Yes, that is one of the questions. (And a corollary of that question is, to what extend was the first uncoded protein synthesis random? Or stated another way, was the distribution of amino acids in these “statistical” proteins biased in some way that made certain functions and resulting structures more probable than others?)
And it’s one there is actual evidence for. Again, the phylogenetically inferred universal ancestors of the aminoacyl-tRNA-synthetases lacked the editing and proofreading domains, rendering them highly promiscous. This is not just some hypothetical gibberish that some biologists dreamt up (though, as you can see in the above papers it was first hypothesized by Carl Woese). Their structures have been elucidated by comparative genomics, biosynthetically resurrected in the lab, and tested for their functions. And they functioned as predicted, though astonishingly also at remarkable levels of catalysis. This then constitutes an actual emprical test of the conjecture that the primordial coding system was very much random.
Heres an overview: [ Charles W. Carter, Jr. Urzymology: Experimental Access to a Key Transition in the Appearance of Enzymes. J Biol Chem. 2014 Oct 31; 289(44): 30213–30220. doi: 10.1074/jbc.R114.567495]
“aaRS Urzymes: Low Specificity, High Proficiency Catalysts
aaRS Urzyme catalytic activities are dramatically higher than estimates for the uncatalyzed rates (Fig. 3A). Notably, Urzymes from both classes accelerate both activation and acylation 10^5–10^6-fold more than necessary to launch ribosome-independent protein synthesis (Fig. 3B). Further, the two classes achieve similar activities with similar masses, consistent with their joint requirement for protein synthesis. Thus, both classes appear to have achieved comparable proficiency increments as their entirely different domain architectures grew comparably in size.
(FIGURE 3.)
Urzyme specificities are low. Spectra for Class I LeuRS and Class II HisRS Urzyme specificities (Fig. 3C) are similar and complementary. Both Urzymes activate a range of non-cognate amino acids. Nonetheless, each Urzyme exhibits an ∼5-fold preference for amino acids from its own class. Unknown differences between aaRS Urzymes and the true ancestral forms may account for some of their promiscuity.
The TrpRS Urzyme provided a unique “molecular knock-out” lacking the entire CP1 and ABD, affording a baseline against which to determine contributions of the two deleted modules. Neither CP1 nor the ABD restored any specificity (15), which results entirely from their energetic coupling.
Using allosteric interactions between genetic modules entirely absent from the Urzymes to enhance specificity resolves challenges (29,–33) associated with failure of rational amino acid-binding pocket point mutants to accomplish anything but reducing catalytic activity. Moreover, generating orthogonal synthetase-tRNA pairs appears to require pruning all amino acid-binding residues to alanine and using random mutation to select rebuilt pockets to match the altered substrates consistent with induced-fit mechanisms (34).
These partial results suggest that aaRS Urzymes could not support a canonical 20-amino acid alphabet. Low Urzyme specificity and the fact that Urzymes cannot utilize the tRNA anticodon for recognition form the first experimental basis for the conjecture of Woese (1, 35) that the first coded proteins were statistical ensembles, without unique sequences.“
That is an interesting question in it’s own right, and not one I can answer with any great certainty I readily concede. I have given arguments for why we might not think this (a code improved towards error minimization) would actually be a hinderance to adaptation, but of course you didn’t agree. Partly because you haven’t got a clue, partly because that’s the hat you’ve put on. The “I think this is all bullshit no matter what”-hat. Interestingly, you haven’t actually given any counter-arguments. As usual, you’ve just declared your resistance to being convinced. Good for you.
But I have to point out that from your perspective, all this is actually completely irrelevant, because you don’t believe evolution is possible even with the remarkable genetic code we have.
To you, all this evolution stuff is all just giant lucky accidents and miracles. You waste no time regurgitating this much over and over agian. So whatever the ability of the canonical genetic code to contribute to the evolution of extant biodiversity is from your perspective an irrelevance. You wouldn’t believe extant biodiversity could have evolved through blind random mutations, genetic drift, HGT, endosymbiosis and natural selection anyway, irrespective of the level of optimization of the code towards error minimization.
Regardless of the extent to which the canonical genetic code has had an impact on the breadth of life’s diversity, it is still a basic fact of protein biochemistry that roughly 98% of sites will be deleterious if substituted. Again, this comes from observation. From compiling the results of lots and lots of studies on amino acid substitutions in proteins the overall picture that emerges is that these proteins are usually well adapted (well adapted, not perfectly) to their current function. So if you change an amino acid, this will usually be deleterious to the protein and through that the carrier organism. As in roughly 98% of the time.
This is what a superior code could protect against. It could make it even less likely for amino acid substitutions to occur, it could make it more likely that IF an amino acid substitution occurs, the one being replaced will be by a chemically similar one, and it could make it even less likely for the formation of premature stop codons.
I have said no such thing. Anywhere.
Really? I think you need to do some work to establish such a tendency. You could start by giving a SINGLE instance of me proclaiming that “I said it so it has been proven”.
Not only is there no such tendency, you will fail to find even a single instance of me making such an assertion. I have not even said that by mistake.
You like to use the word bullshit a lot. But you’re the only one here actually bullshitting. You simply sit there and make shit up.
Okay, skeptic hat is *on*.
Okay, you have now accused me of that. I now respond that, in fact, I’m not Gish-galloping and that everything I said was both there to help you understand what we’re talking about (you didn’t know what the genetic code even was), but was also entirely pertinent to the points you make.
You must mean genetic code, not genome. They’re not the same thing.
I have not given a reference in support of that claim, the references I gave was direct responses to what you asked for. You wanted evidence of mutations in the code that affects how the code responds to mutations. I gave you that evidence. With an example at the amino acid level at a particular location in a particular enzyme from the translation system. That is what I responded to because that is what you asked for.
I’ll deal with the rest of your crap later when I have time. Suffice it to say, as usual you actually have no goddamn clue what you’re talking about, and you don’t even seem to understand the things I quote to you from references. You really should just go read that wikipedia article on the genetic code. Thrice. Then we can maybe start to have a conversation.
Are you aware that Woese himself doesn’t believe that natural selection was the mechanisms by which these systems evolved.
I guess he also doesn’t know what you are talking about.
I see zero reason to conclude that because any universal ancestors (again Woese disagrees with you on that as well) lacked the editing functions, that this shows that the coding system was random. You said it so it is proven?
So there’s that…
This was quoted from the paper:
They lied!!
HAHA oh lord this one just keeps digging.
No this is incorrect. I wanted evidence of mutations to the code that affects how the code responds to mutations TO THE CODE, that would be deleterious to the CODE.
phoodoo,
No, they did not lie. The increased antigen diversity is not brought about by an increase in genetic variation, but by a lowering of translation fidelity.
I repeat: you are confusing gene expression and genomic sequence.
Corneel,
How would have me saying “they evolved the ability to increase the translation of more mutations, in order to give more plasticity for defending against more host defenses…” have changed the point? It is the authors who have said their theory is that they evolved this, not me. I was simply pointing out that organisms have the ability to use increased mutations or decreased mutations depending on their needs, thus we see examples of both robust genomes and genomes which appear to be intentionally NOT robust, but rather plastic and changeable. So if Rumraket is giving examples of BOTH robustness and plasticity, how is that helping his argument in any way?
That is describing a genome which adapts (and code which allows it) not a code which does not allow adaptability under different circumstances-as you stated a lowering of translation fidelity, because it evolved this and it is useful, and sometimes presumably a more stable translation fidelity for other organisms, almost as if on cue.
That is what you recieved. Literally exactly that.
Let us review what you said and what my response was. You ask:
Then I respond to this directly, the following way:
And I give a link to a paper on pubmed, and explain what it says in this way:
The ONLY way you can think that this isn’t what you asked for, is if you don’t understand what this says and how it relates to the genetic code. So I will now attempt to explain it to you so you can see that you in fact recieved what you requested (actually, what you declared nobody could explain).
First of all, the genetic code is NOT the genome of some given organism, as you seem to have mistakenly thought now several times. So if we are to make any progress, you really need to understand that genome and genetic code are two different things.
To that end: You might occasionally hear somebody INCORRECTLY use the term in a sentence when referring to some person’s, or organism’s genome. It’s a popular phrase in various TV crime dramas, where actors playing forensics experts will say shit like “we confirmed the match to his genetic code” or “we read his genetic code” or something along those lines. That is an INCORRECT use of the term. What they SHOULD be saying is that they have matched their sample to a piece of his ‘genomic sequence’, or just his ‘genome’.
The genetic code is the ruleset of the translation system. And when I use the word ‘ruleset’ I’m using a metaphor. It is not literally a ruleset, we just call it that because it’s a convenient way to think about it. The translation system is the collection of molecular machines and enzymes that “read” your genomic sequence, and TRANSLATES it into proteins.
So when your cells make proteins, they do it by TRANSLATION of RNA sequence into amino acid sequence. So chains of RNA nucleotide molecules are read, and chains of amino acid molecules are stuck together. These amino acid chains will subsequently fold into specific structures. We call them proteins.
That means it reads the nucleotides that make up RNA, and convert what it reads into amino acid sequence (proteins are made of strings of amino acids).
So very simplistically, a long string of RNA is “read” by a molecule called the ribosome, and this molecule can in some sense “translate” the string of RNA nucleotides it reads into strings of amino acids.
I have left out some details here because they’re not necessary to understand (yet). I have attached an animated gif from the wikipedia article on the ribosome that shows the process of translation. The black string at the bottom is the RNA molecule being “read”. The big green and yellow clumps are the Large and Small ribosomal subunits. If you stare at it for a while you will see the growing chain of amino acids (the protein being made) come out the top of the ribosome.
The dark blue things are tRNA (Transfer-RNA). They are called that because they are made of RNA, and they literally transfer the amino acids to the ribosome. They are part of the translation system.
This is where it gets relevant to what you asked for. Something is missing from the animated gif, from the process of translation, which is a specific chemical reaction called aminoacylation of transfer-RNA. This is something that takes place before what we see in this animated gif.
What this basically is, is a process by which the dark-blue molecules “pick up” the correct amino acid. To accomplish this correctly, an enzyme is involved that covalently binds the amino-acid to the tRNA molecule. THIS is the first step of translation, the binding of an amino acid to tRNA. It is catalyzed by the enzyme called aminoacyl-tRNA-synthetase (abbreviated aaRS). So named because of what it does (amino-acylation), and what it does that to (tRNA).
This chemical reaction is part of the fidelity (as in the accuracy control) of translation. So any mutation that affects the accuracy of the aminoacyl-tRNA-synthetase, in turn affects the translation system, and thus affects the amino acid-to-codon assignment of the genetic code. Thus, affects the genetic code.
So a mutation that causes aminoacyl-tRNA-synthetase to stick the wrong amino acid onto a tRNA molecule, in turn has affected the assignment of codons to amino acids for the genetic code for the host organism (for that particular tRNA’s cognate codon). Because if this aaRS occasionally puts the wrong amino acid on tRNA, it means that the particular codon this tRNA interacts with, now effectively “codes for” the other amino acid too. Which means that if this organism now gets a mutation in a coding region that causes an amino acid substitution, there is now some chance this aaRS molecule will be involved and use the “wrong” amino acid. If the wrong amino acid is occasionally used, then the aaRS which is itself a protein in the translation system, will in turn be affected the next time an aaRS enzyme is being synthesized so it can participate in translation. So it’s a mutation to the code (specifically, the aaRS molecule), that affects how the code responds to mutations to the code.
It would literally not be possible for me to answer your request (read: declaration that nobody could explain this) more correctly, or directly, than what I did.
Carl Woese is dead, so he no longer holds any beliefs. Anyway, Carl Woese was pretty clear that natural selection was not the only mechanism of evolution, and that it was not the only factor that affected the code’s evolution. I have not stated, nor do I believe otherwise. In fact I have stated the commonly held view, that at least four factors contributed to the origin and evolution of the genetic code we have and see today. Only one of which is natural selection.
I don’t merely guess this, I’m certain of it. He’s dead. When he was alive, he basically fathered much of the stuff I’m right now informing you about. Ironically In a certain metaphorical sense I’m basically channeling Carl Woese.
I think that you don’t have even the slightest clue about what Carl Woese thought about anything and you’ve just tried to google some shit you barely (as in, not at all) understand. I suspect you’ve managed to misinterpret one of his conjectures that the last universal common ancestor was not a single cell prokaryote, but rather a community of cellular-like entities undergoing rampant HGT, and now you in your painful ignorance thinks you’ve dug up some kind of gotcha.
The universal ancestors I spoke about above in my previous post was not the universal ancestor of the three domains of cellular life, but the universal ancestors of PARTICULAR MOLECULES. Specifically the ancestral molecules to the class I and class II aminoacyl-tRNA-synthetases I just told you about.
This much was actually clear when I first wrote it if you had bothered to read for comprehension. I was talking about individual molecules, not species of cells.
It was fucking Carl Woese himself that first hypothesized that these aaRS molecule classes had two common ancestors, and that they were extremely promiscous and that they synthesized statistical proteins at the origin of the genetic code. So no, Carl Woese didn’t disagree with me, or not know what I was talking about, he literally first posited these things himself in NINETEEN SIXTY FIVE. I got it from him.
That’s the only rational conclusion since the missing domains is what ensures the fidelity of aminoacylation against misincorporation.
What part of the ancestral enzymes have been biosynthetically resurrected and tested for function and found to confirm Woese’s hypothesis is escaping your comprehension here?
If you in the face of that still see “zero reason” to conclude that primordial translation was statistical, then I submit that you are actually cognitively blind to both empirical evidence and reason itself.
No, hypothesis was confirmed by experiment, so therefore it’s an evidentially supported conclusion. Nothing is “proven”. If you want proof, science isn’t for you, go study pure mathematics.
.. and then I forgot to attach it. It should be here now.
https://upload.wikimedia.org/wikipedia/commons/2/21/06_chart_pu3.png
phoodoo,
The plasticity in this system is phenotypic whereas the previously discussed robustness concerned genetic mutations. The Mycoplasma parasites may very well be highly intolerant of novel mutations and thus NOT be adaptible in an evolutionary sense (I actually don’t know, the paper doesn’t mention this).
Whether or not rumraket convinced you (an impossible task, IMO) is entirely irrelevant to whether you ought to be grateful for all the time and trouble he’s taken trying to explain this (to me extremely complicated) material. That’s what I was saying.
You just prefer to fight though. It’s a common internet thing, I believe.
3 to 4% of children are born with a genetic disease or major birth defect. More than 20% of infant deaths are caused by birth defects or genetic conditions.
Is that really the best your designer could do?
Of course those who argue and scratch their heads over how life could have originated all agree on one thing, it must have been a blind, accidental, bottom-up process.
It would be sacrilegious to entertain the idea that physical matter is fundamentally part of a living system. And rather than the first earthly life just appearing from dead matter, it actually condensed from a more subtle form of life. Top down rather than bottom up. Just look at how elements such as carbon, hydrogen and oxygen are so suitable and capable of combining in such a way as to produce complex life. Its as if they were made for the job 🙂
Before these ideas are condemned as being too far fetched to contemplate consider the way in which the chalk formations seen in such places as the white cliffs of Dover were formed. It is an example of dead matter being produced by living forms.
The development of any living organism is always found to begin with a cell and nothing less. What I am advocating is that it is the same for earthly life as a whole; it began with a functional cell and nothing less.
CharlieM,
Other than the fact that the idea gets you off, why do you believe this? Evidence and argument, please.
Yes Phoodoo, you are only being insulted for your own good. It is time for you to thank your superiors, toe the line, and desist from questioning the authority of experts.
The same physical laws and constants that govern the chemistry of carbon, govern the chemistry of silicon and oxygen. Was the entire universe set up to produce lots of sand? You heard it here first!
In contrast to the people who argue and scratch their heads about how a blind, accidental, bottom-up process could produce life, we have here on the other side the people who are absolutely convinced that a wizard did it.
If you define life to be restricted to cellular life, then yes, life began with the appearance of the first cell.
That just means that everything that lead to the emergence of that first cell, would not qualify as life under the definition you use.
It doesn’t mean the constituents that came to make up the first cell did not undergo some sort of physical and chemical process that resulted in that cell.
Well, Walto, you consider yourself to be a smart guy don’t you. I assume you are pretty smart.
So when Rumraket says something like:
Has he convinced you that, because some ancestral population lacked some editing functions, and the extant population contains such editing functions, that the ONLY logical conclusion is because it was a random event? Are you convinced by this? Is this the only conclusion YOU would draw? If so, maybe you can explain to me why this is the only conclusion one could draw.
Does one really need to understand every detail of the entire coding process to say this? Does one need to know which codon is assigned to which amino acid to make this conclusion? But this is pretty much what Rumraket is trying to persuade us all of.
So you tell me, why are you so convinced by this? Because it sounds technical?
Really, so expecting him to do a little bit of homework so he can actually start competently asking questions, is to be insulted? He didn’t even know what the genetic code was. Telling him he should remedy this before attempting to argue against the possibility of the code’s evolution is to insult him? Gimme a break.
No, it’s simply time to try to understand what we are talking about, before you attempt to argue it’s all bullshit.
He can question the experts all he wants, but he should be expected to be able to explain why the experts say the things they do if he wishes to argue it’s all wrong. You can’t rationally argue against something if you don’t first understand it.
Do they?
I particularly question the “must” part of that. They might presume that it was such a process, but many would not use “must” there.
Oh, and what’s a “bottom-up process”? I understand “bottom-up” as a qualifier for “design” or for “description”. But I don’t know what it means as applied to “process”.
Rumraket,
I understand your argument just fine.
And your argument is completely lacking in justification. Sorry if you feel insulted by that.
You don’t even seem to understand that Woese completely disagrees with your conclusions. Woese was wholly against accepting that Darwinian evolution was responsible for the existence of the genetic code. In fact, he believed that practicing biologists had no use whatsoever for Darwinian evolution in the course of their work.
You don’t even understand this, so I am not sure why you are congratulating yourself so vehemently. I guess its just what you do.
You go from saying A is true, so therefore B is true, without ever being able to connect the two rationally. Its not a protein problem, its a logic problem. That’s is your deficit in thinking.
I never said it was the only logical conclusion. I said it was the only rational conclusion. I try to be precise with what words I use.
There are strictly logically other possibilities. There always will be. No matter what evidence we actually have, it will always be logically possible to rationalize it all away in ad-hoc fashion. But those would be possibilities not-in-evidence. In other words, not rationally supported. They would be ad-hoc. After the fact rationalizations.
It could sit here and make one up right now. Another mere logical possibility. For example, we could posit that subsequently to charging a given tRNA with an amino acid, an entirely different enzyme than the aminoactyl-tRNA-synthetase comes along, then interacts with the tRNA anticodon, and then chemically modifies the amino acid into the “correct” one that corresponds to the particular tRNA anticodon.
It would be a conclusion for which there is zero evidence. It is strictly speaking a logical possibility. But there is zero evidence from comparative genomics, that there was ever a stage of life with a whole host of post-aminoacylation chemical modifications of amino acids charged on tRNA.
So the conclusion we have suggested here is not one the evidence lead us to, it is one we make up in spite of what the evidence we have actually shows. So we are NOT following the evidence wherever it leads. Instead we are making shit up to lead ourselves away from where we don’t want to go.
In this case, apparently we seem to want to believe, in spite of what comparative genomics tells us, that there just could not possibly have existed a stage of life with a statistical translation system. So given that we are deeply emotionally invested in this not being possible, we are going to make up stories about how the evidence we have before us is wrong and something else must have been the case. Or at least, the mere fact that other conclusions are logically possible means that the evidence we actually do have, just isn’t good enough.
Furthermore, we initially set out to try to explain the origin of the genetic code and the translation system. That was the challenge we had before us. So we made a hypothesis based on some data we had at the time. And this hypothesis made some predictions. So later on, we collected some more data, and this new data is what our hypothesis predicted it should be. But because we don’t like this hypothesis, for reasons we are unable to articulate, we’re going to just throw away our hypothesis. We’d rather make shit up about why the evidence we have is wrong, and be left with still no explanation for the origin of the genetic code.
Precisely! And this is why your argument is so ridiculous, but you still don’t get it!
YOU ARE THE ONE, who posited THIS as an example of why we can say the origin of the genetic genetic code was random, NOT ME! This was the example YOU used. This was literally the example you came up with. I didn’t come up with this example out of the blue you did. YOU are the one who completely obfuscated the point.
And now you are scratching your head about why I find it incredulous that you are saying that. Maybe you need to hit pause and think for a bit.
I can’t help it if Walto is so impressed with your convolutions. I am not.
Rumraket,
And not only that, you then doubled down on your example, saying, not only are there many redundancies which prevent poor translation of some proteins, but there are some bacteria which have evolved to do just the opposite, so see, look, the code must be random! Apparently you felt if you just threw in a technical enough looking study, that this would be a great way to impress Walto.
Why you thought the example of mycoplasm was useful in anyway towards your discussion, other than to further try to impress that you can find technical documents, is beyond me. I believe it proved exactly the opposite, that the code is extremely versatile in its use of translating proteins, NOT random and certainly not an example of how other codes would certainly be so much better!
Thank you for this pile of vague, unevidenced assertions. Now I would like for you to go and back up all of them, with references and arguments. Start at the top, pick the first assertion, then back it up.
Your first assertion is that you understand my argument. I’m not convinced. First of all, my argument about what? We have argued quite a lot of different and some times related points now at this stage. Impress me by correctly re-stating my argument, in your own words, without misrepresentating it. You don’t have to agree with it. I just want you to show that you really do understand it, by making the same argument yourself in different words than I have used.
Your second assertion, that my argument (which one?) is completely lacking in justification is a pretty bold claim. Not even sure how you could really back this one up.
Then follows lots of crap about Carl Woese. I want references for all of it. Every single one.
Woese completely disagrees with your conclusions. <- This must mean you have references to Woese's work wherein he directly contradicts something I "conclude". Give me an example. Start by quoting me making this conclusion (quoting, not re-stating in your typical caricature form what you think I’m concluding), then quoting Woese contradicting it.
Good luck with this one.
Woese was wholly against accepting that Darwinian evolution was responsible for the existence of the genetic code. <- This one has so much confused terminology it's hard to say whether I agree or disagree with it, because I'm actually not even sure what you mean. I'm pretty confident you don't actually know yourself.. So instead you should find me where I say that "Darwinian evolution" is responsible for the "existence" of the genetic code.
Even were that to be the case, it has zero relation to anything I’ve said here. Whether practiciing biologists has any use whatsoever for Darwinian evolution in the course of their work is immaterial for the purposes of our “discussion”.
Well, that’s good news! If we are ever in a discussion about whether or not there was ever a stage in life with a whole host of post-aminoacylation chemical modifications of amino acids charged on tRNA, I will be sure to remember this. Perhaps that is part of a discussion you once had with someone.
In the meantime…the genetic code is random?
Other than speculation why do you believe life started from physical matter that was less than a cell?
The genome can do nothing without the context of its surrounding cellular environment. There are convincing arguments that the cell controls the genome and not the other way round.
Ken Richardson:
Stephen Talbott:
I believe that lifeless matter can, by itself, begin to coalesce and then reproduce itself just as much as I believe that a feather could just appear from nowhere without the context of the animal in which it originated. Where is your evidence that life began in the way you believe it did?
You may have heard this before, but just a reminder:
Incredulity is not an argument.
Care to make one?
No evidence nor argument has been seen.
Just another deflection by CM:
A dickhead for life.
It would appear that it is impossible to avoid the fine tuning argument, even in biology.
Do you realize the phrase ‘genetic code’ doesn’t even appear in the linked article?
This is somewhat hilarious. It’s the materialists like Rumraket who are forced to appeal to laws and constants. If they don’t, then ‘chance’ becomes their god. And they don’t like to admit that.
Really. He managed to compute every single possible fitness landscape for the genetic code. Remarkable. And you believe that, do you?
His expectation needs a scientific basis, which it currently lacks. So it’s not legitimate.
It doesn’t mean it wasn’t designed, because that doesn’t logically follow, and you know it, and so avoid making that claim. Unlike Rumraket.
Any old code should suffice and I have a computer program which proves it!
Thank God he wasn’t talking about the evolution of the genetic code!
Or less. LoL.
Are you saying that Woese believed in the random evolution of the genetic code?
So you agree with phoodoo? Amazing!
Her name is Chance. She is a goddess. Worship her.