Recently, I was browsing through the latest posts over at Evolution News and Views, and an anonymous article titled, Imagine: 60 Million Proteins in One Cell Working Together, caught my eye. By now, most readers at TSZ will be aware that I consider it overwhelmingly likely that the first living thing was designed. However, I’m also highly critical of attempts to over-egg the case for intelligent design. The article I read was one such attempt: it contained some unfortunate errors and omissions.
The author tried to bolster his case by quoting from two articles in the same issues of Nature (volume 537, 15 September 2016): one by Aebersold & Mann, and the other by Huang, Boyken, and Baker. As it turned out, neither paper was about the origin of life: one was about the proteome (or the set of all the proteins in a cell), while the other discussed de novo protein design.
How many proteins are there in a single cell? And how many are needed?
The ENV article was titled, Imagine: 60 Million Proteins in One Cell Working Together. When I first saw that headline, I was a little puzzled. When I hear the phrase, “60 million proteins,” I automatically assume the speaker means different kinds of proteins. But what the author actually meant was: 60 million protein molecules inside a single cell.
“What kind of cell?” you may ask. Apparently the figure of 60 million is taken from a passage in the Nature article by Aebersold & Mann, where the authors are relating some astonishing facts about the proteins in a tiny yeast cell:
A proliferating Schizosaccharomyces pombe cell contains about 60 million protein molecules, which have abundances that range from a few copies to 1.1 million copies per expressed gene.
However, yeast cells are eukaryotic: they have a nucleus. The first living thing didn’t: it was prokaryotic, and it would have been much smaller than a yeast cell. How much smaller? We don’t know. But it turns out that the number of protein molecules in a tiny cell belonging to the bacterium Mycoplasma pneumoniae is only 0.05×106, or just 50,000. That’s three orders of magnitude less than the yeast cell described by Aebersold & Mann.
But the real question we need to ask is: how many different kinds of proteins are there in a simple bacterial cell? It turns out that a typical bacterium requires 4,000 proteins for growth and reproduction, while humans require more than 100,000 different kinds of proteins. Some bacteria, however, need far fewer than 4,000 proteins, according to MicrobeWiki:
In 1995, the entire genome of M. genitalium was sequenced in less than 6 months using the random shotgun sequencing technique. It was found to have the smallest known genome of any free-living organism at about 580 kilobase pairs long, with 479 coding sequences for proteins. For comparison M. pneumoniae has 677 protein coding sequences, H. influenzae has 1703, and E. coli K-12 has 4,288.
382 of the 482 protein-coding genes in Mycoplasma genitalium have since been identified as essential. Dr. Stephen Meyer, in his work, Signature in the Cell (New York: HarperOne, 2009), generously estimates (ibid., p. 213) that a minimally complex cell needs 250 different kinds of proteins. Dr. Michael W. W. Adams, in an article titled, The Influence of Environment and Metabolic Capacity on the Size of a Microrganism, makes a similar estimate: in a nutrient-rich environment, a life-form with a minimal biosynthetic capacity would require at least 250 genes.
So the first cellular life-form probably required 250 different kinds of proteins, in order to function. That’s still a pretty impressive number.
What proportion of amino acid sequences are functional?
The Evolution News and Views article refers to the recent article by Huang, Boyken, and Baker, before going on to cite the pioneering work of Intelligent Design researcher, Dr. Douglas Axe:
This paper is interesting because it relates to the work of Douglas Axe that resulted in a paper in the Journal of Molecular Biology in 2004. Axe answered questions about this paper earlier this year, and also mentioned it in his recent book Undeniable (p. 54). In the paper, Axe estimated the prevalence of sequences that could fold into a functional shape by random combinations. It was already known that the functional space was a small fraction of sequence space, but Axe put a number on it based on his experience with random changes to an enzyme. He estimated that one in 1074 sequences of 150 amino acids could fold and thereby perform some function — any function.
I’ll return to Dr. Axe’s estimate in a moment. The Evolution News and Views article went on to breathlessly declare that Axe’s figure of 1 in 1074 had actually been too generous, and that the true proportion of 150-aa sequences capable of performing a biological function was hundreds of orders of magnitude smaller (green bolding below is mine – VJT):
The new paper in Nature seems to point to a much smaller functional space. The authors say,
It is useful to begin by considering the fraction of protein sequence space that is occupied by naturally occurring proteins (Fig. 1a). The number of distinct sequences that are possible for a protein of typical length is 20200 sequences (because each of the protein’s 200 residues can be one of 20 amino acids), and the number of distinct proteins that are produced by extant organisms is on the order of 1012. Evidently, evolution has explored only a tiny region of the sequence space that is accessible to proteins.…
Since 20200 is about 10260, and the space actually sampled by living organisms is 1012, the numbers differ by at least 240 orders of magnitude for proteins of length 200, or about 183 orders of magnitude the 150-amino-acid chains Axe used. No wonder the authors say that “the natural evolutionary process has sampled only an infinitesimal subset” of sequence space.
This, I have to say, is a complete misreading of the paper in Nature by Huang, Boyken, and Baker. The authors are not trying to answer the question explored by Axe – namely, what proportion of 200-amino acid sequences are capable of performing a useful biological function? Rather, what they are estimating is the proportion of possible 200-amino acid sequences which are found in nature. Their answer is: 1012 divided by 20200 (which is approximately 10260), or in other words, 1 in 10248. But instead of concluding that any amino acid sequences which are not found in nature are non-functional, as the writer of the Evolution News and Views article appears to do, they draw the opposite conclusion: “The huge space that is unlikely to be sampled during evolution is the arena for de novo protein design.” In other words, there are a whole lot of new proteins out there which nature hasn’t created yet, but which scientists can create.
Back to Dr. Axe’s estimate of the proportion of 150-amino acid sequences which are capable of performing a biological function: I have previously discussed his figure of 1 in 1074 in my online review of his latest book, Undeniable: How Biology Confirms Our Intuition That Life Is Designed (New York: HarperOne, 2016). I quoted from various professors, including an expert in protein structure who argued that the proteins in the first living things would have all contained considerably less than 100 amino acids:
So I think the counterargument to the ID folks is not that sequence populations of 10E80 needed to be searched to find a 100-mer with robust enzyme activity, but rather that random populations of a few million relatively small proteins could contain a few molecules from which to start the evolutionary process.
Another professor whom I cited regarded Dr. Axe’s work as highly biased, because he had based his studies and calculations on very large sequences of amino acids (150-amino acid chains), even though much shorter sequences (such as polypeptides) were known to have biological functions.
Additionally, I quoted from a third professor, who kindly pointed out to me that because a very large number of different amino acid sequences were capable of performing the same biological function, the actual number of attempts that would be required to make a molecule with the same function as one of these proteins was likely to be much lower than 1060 or 1080. This professor also estimated that the number of attempts that would have been available to evolution had been estimated at 1042 – far greater than the number of attempts that could be made by doing man-made experiments (no more than 1012, which means that any protein which is too difficult for human experiments to generate might still be created by natural processes). This professor added that that while he was very sympathetic towards arguments against the natural origins of the first cell, and while he thought Dr. Axe may well be correct in arguing that abiogenesis was astronomically unlikely, in his opinion, Dr. Axe seemed to be trying to calculate the probability of an unknown process, and was therefore overstating his case.
Bottom line: we don’t really know how rare functional 150-amino-acid proteins are in sequence space, and we don’t know that they couldn’t have been derived from shorter proteins.
How did life get to be left-handed?
The Evolution News and Views article went on to say that there were
Axe’s estimate of one in 1074, one must note, referred to mutations to existing proteins in the universal proteome of all organisms. When considering random chains of amino acids in a primordial soup, however, Steve Meyer noted in Signature in the Cell (pp. 210-212) two other requirements. The amino acids must be one-handed, and they must form only peptide bonds. Applying generous probabilities of 0.5 for handedness and 0.5 for peptide bonds, Meyer reduced the probability for a lucky functional protein chain of 150 amino acids to one in 10164, far beyond the universal probability bound (p. 212). [Green bolding mine – VJT.]
The problem of life’s one-handedness which Dr. Meyer raises in his book is a genuine one: without homochirality, life would not exist.
A recent article by Denise Henry in Phys.org, titled, Discovery demystifies origin of life chirality phenomenon (March 11, 2015) describes a promising breakthrough in the field:
University of Akron A. Schulman Professor of Polymer Science Tianbo Liu has discovered that Mother Nature’s clear bias toward certain amino acids and sugars and against others isn’t accidental.
Liu explains that all life molecules are paired as left-handed and right-handed structures. In scientific terms, the phenomenon is called chirality…
Liu found that any molecules, if large enough (several nanometers) and with an electrical charge, will seek their own type with which to form large assemblies. This “self-recognition” of left-handed and right-handed molecule pairs is featured in the March 10, 2015, issue of Nature Communications.
“We show that homochirality, or the manner in which molecules select other like molecules to form larger assemblies, may not be as mysterious as we imagined,” Liu says.
In their paper, Liu et al. summarized their results as follows:
In summary, chiral macroanions demonstrate chiral recognition behaviour by forming homogeneous blackberry structure via long-range electrostatic interactions between the individual enantiomers in their racemic mixture solutions. Adding chiral co-anions suppresses the self-assembly of one enantiomer while maintaining the assembly of the other one. This leads to a natural chiral selection and chiral amplification process, indicating that some environmental preferences can lead to a complete chiral selection. The fact that the relatively simple inorganic macroions exhibit chiral recognition and selection during their assembly process indicates that the related features of biomacromolecules might be due to their macroionic nature via long-range electrostatic interactions
Another, more recent paper in Chemistry World by Dr. Rachel Brazil, titled, The origin of homochirality provides an excellent overview of the work in the field done to date, and discusses new findings. Dr. Brazil puts forward her own hypothesis.
Readers may still be wondering: why are the amino acids in a protein linked by peptide bonds, instead of non-peptide bonds? I’d like to invite any biologists who may be reading this post to weigh in on this subject.
What the ENV article got right
The Evolution News and Views article redeems itself at the very end, when quoting from the paper by Huang, Boyken, and Baker. The authors state:
Despite the advances in technology of the past 100 years, human-made machines cannot compete with the precision of function of proteins at the nanoscale and they cannot be produced by self-assembly.
The authors go on to suggest that the extreme efficiency of these nanoscale proteins is the due to the fact that “selective pressure operated on randomly arising variants of primordial proteins, and there were also hundreds of millions of years in which to get it right.” But this is pure speculation. As the author of the ENV article aptly puts it:
Now ponder that. They are duly impressed by the intricate molecular machines that proteins make in the cell, yet their worldview does not allow them to consider this as evidence for design.
Indeed.
What I am arguing in this post is that while I see no reason in principle why nature cannot generate proteins capable of performing useful biological functions, and while the mathematical arguments against such proteins originating by natural processes strike me as inconclusive, it seems to me perfectly reasonable to ask why the proteins we observe in nature are capable of technical feats which even our best scientists cannot match. It is not enough to simply invoke “hundreds of millions of years”: this is lazy scientific thinking, which makes no testable predictions. In the absence of such predictions, intelligent design of these nano-machines by a super-intellect sounds like a plausible explanation which warrants consideration.
Here’s one questions I’d like to ask the biologists: do the most efficient nanoscale molecular machines tend to be relatively short (as we’d expect if they arose naturally) or relatively long?
Readers who would like to know more about the difficulties attending abiogenesis are welcome to view Dr. James Tour’s online talk, “The Origin of Life – An Inside Story,” here or here. The take-home message of Dr. Tour’s talk was that currently, scientists know nothing about how the ingredients of life originated, let alone life itself. Dr. Tour makes no attempt to “sell” intelligent design to his audience: indeed, he formulates his argument without even mentioning it. Readers will find it highly watchable.
No, relatively short proteins (which are used by nano-machines) are easier to arrive at de novo, while long proteins allow for more possibilities. We’d expect relatively long proteins to be more efficient, and so to evolve relatively incrementally from the shorter evolutionary precursors.
Glen Davidson
It’s enough to invoke a “super-intellect” but not “millions of years”? Why?
Actually, I think that, were we truly lacking in evolutionary predictions and observable constraints resulting from evolution there would be some excuse to at least consider a super-intellect as a hypothesis. The limits of intelligence are not in sight, and not known, after all. That said, if we’re really treating it like a scientific hypothesis we’re going to have to do more than just bring up a super-intellect, we’d need some predictions. Like designs not being constrained by heredity. Do we see that? No, we really don’t.
And biologists don’t just say “millions of years,” of course, they actually do predict that life will be constrained by heredity, by contrast with reasonable expectations of design. Is life constrained by heredity? Why, yes it is. That is why evolutionary theory is favored over any design hypothesis, while it is supported by both genomes and by paleontology.
Design can be considered, but it has to be open to testing by the actual entailments of known design (unknown design that is unlike known design is simply unknown and cannot be a meaningful hypothesis). Same for evolution. The thing is, the entailments of evolution are what we observe, not the entailments of known design.
Glen Davidson
Yeah that is really confused. Nobody thinks molecular machines arise de novo(whether “short” or “long”). Rather the idea is they evolve incrementally from aggregations of individual proteins into larger functional complexes. And the proteins themselves either arise from gene fusions of smaller fragments, de novo from non-coding DNA or by divergence of duplicates.
Take as an example a model for the origin and evolution of the ribosome: History of the ribosome and the origin of translation.
At no point in this model does a molecular machine consisting of multiple interacting proteins, whether three, eight or forty of them together, just suddenly pop into being by luck as if assembled by a tornado in a junkyard. It’s slow accumulation of proteins and extensions of RNA structures over tens if not hundreds of millions of years before even the last universal common ancestor.
Besides that I generally agree with what you write Sal. I don’t understand this incessant need to laughably oversell this crap. As if it wouldn’t be enough if the rarity of functional proteins in amino acid sequence space was 1 in 10^64. If that was really an accurate number I would totally agree with Axe, evolution would be impossible. They really don’t have to go and artificially inflate that crap. What a total circus. I can see how the drooling deencephalized sycophants on UD would just gobble it up.
And thank you for inadvertently reminding me I need to finish that OP on this issue I promised to do.
Rumraket,
It’s vjtorley, not Sal.
That would probably be true if it is a free-living cell that has to synthesize it’s basic constituents from simpler precursors found in the environment. One would be hard pressed to see how a free living cell that has to biosynthesize it’s own DNA, RNA, lipids and amino acids and run basic functions of growth, replication and division could do with less.
But what if it is not a free living cell? What if replication and division was due to a local physical cycle like convective flow? Or spontaneous aggregation of lipids into vesicles that grown and divide by themselves? How little could it get by with then? I don’t know, do you? Will we finally find a hole we have to plug with a God or will nature win this eleven millionth race also?
ID’s output consists largely in gee-whiz figures.
The ENV article: You know those gee-whiz numbers? They’re even gee-whizzier than you thought.
God, QED.
Glen Davidson
Ahh lol, why the hell do I mix those two up? 🙂
Not by their respective levels of engagement with the issues.
VJT does.
Glen Davidson
Thus God, even more. QED.
VJ Torley:
You know better than that. Joshua Swamidass might have written much the same thing, were he working in that field. It would have been a consequence of his view of science, not his view of the world.
What you probably don’t know is how conservative Christians in the United States are “educating” youth to dismiss immediately science that conflicts with their Bible-based worldview, and to “explain” it as a consequence of an
incorrect[edit: evil] worldview. (If you want to know, dig into Focus on the Family’s video series The Truth Project. It’s a very big deal among evangelicals in the U.S. There are usually a number of episodes available at YouTube. Associated instructional materials are also online, and well worth reading.) In short, worldview is used here in the most anti-intellectual of ways. Honestly, I don’t think you would want to be a part of it if you knew the broader context.Huang, Boyken, and Baker: “Evidently, evolution has explored only a tiny region of the sequence space that is accessible to proteins….”
ENV: Since
is about 
, and the space actually sampled by living organisms is 
the numbers differ by at least 240 orders of magnitude for proteins of length 200, or about 183 orders of magnitude the 150-amino-acid chains Axe used. No wonder the authors say that …
Huang, Boyken, and Baker: “… the natural evolutionary process has sampled only an infinitesimal subset” of sequence space.”
Huang, Boyken, and Baker: “The huge space that is unlikely to be sampled during evolution is the arena for de novo protein design.”
Douglas Axe: “… search … search … search … search … search… search search SEARCH search search…”
Tom English: As I’ve pointed out before, it’s ludicrous for Axe to explain that evolutionary “search” doesn’t really search, and to keep saying search anyway.
Protein molecules are proteins.
From the OP:
It is possible that the first cell was eukaryotic and the prokaryotes descended from eukaryotes. If that is not a possibility, why is it not a possibility?
From the OP:
I don’t understand why that is ‘the real question we need to ask.”
Is the actual number of proteins of a certain “type” less important than the number of “types” in order to ensure meaningful growth and reproduction?
Mung,
I don’t understand why VJ thinks asking another question, rather than the one he thinks they should ask, is considered errors and omissions.
I am pretty sure VJ doesn’t know what the first cells were like.
Vj,
Nice to see you posting here and I appreciate critical analysis of ID writings. I myself have been 15% critical and 85% supportive of ID literature.
First, this is really bad from Liu:
Living systems are organic, not inorganic! Why doesn’t he try this with the amino acids of life? This isn’t exactly on the up and up, in my humble opinion.
Regarding homochirality, a lot of these researchers ignore experimental evidence that even if a proto-protein starts out homochiral, it won’t stay that way very long in geological time because of thermal agitation, it will become racemic (hetero chiral) just do to thermal agitation.
Whatever gains the supposed researchers found will be erased relatively quickly in geological time. I’ve seen published experimental half lives from hours to a few centuries. There are some claims of slower half-lives that are based on dubious interpretations of the fossil record rather than actual lab observations.
Also, when Sidney Fox took homochiral amino acids to start with (bean paste) and then tried to connect the amino acids to form proteins, the amino acids lost their homochirality.
VJT, nice to see you posting here!
And I appreciate critical analysis of ID writings.
I myself have been 85% critical and 15% supportive of ID literature.
Its a important point to say that invoking time is not invoking evidence for mechanism. Evolutionists got away with this crazy idea for too long.
If time does everything then everything can be done with time.
Its just a line of resoning to say time plus evolution can and did create such and such.
Creationists should hold evolutionists to a scientific methodology which rejects mere timeline explanation.
Vj,
There is the unfortunate assumption that time is the friend of evolving complexity for OOL. I see the opposite. If we let a proto-protein sit in water, it will spontaneously break apart through hydrolysis reactions over time.
I think James Tour/Jonathan Wells’ Humpty Dumpty problem encapsulates the intuitions correctly, the work of Axe tries to put figures to this.
Now, there is incentive from the medical community to study enzymes and the critical parts of them, so I expect we will have more and more data as time goes on. The issues raised are far from settled.
Rather than going into how many amino acids are needed to make function, these generalization are too vague. It will be helpful to see the numbers for specific enzymes critical to life.
Now, just as there are an infinite number of ways to make a watch, there are probably an infinite number of ways to make a chemical replicator. But having an infinite number of ways to do such things doesn’t make them highly probable. A tornado going through a junk yard won’t make a new kind of watch.
There may be an infinite number of ways to create a gear for a watch but coordinating the right size of gears makes the problem of building a watch improbable even though there are an infinite number of ways to build a watch.
In like manner, there may be an infinite number of enzymes possible, but to have enzymes that fit together and work together as critical parts in a chemical replicator makes such replicators improbable.
If we were interested in only chemical replicators in general rather than complex replicators, one could just as well look a salt crystals. They replicate. The problem of life is that it looks like a Rube Goldbergesque complex chemical replicator.
Here in this video is just some proteins involved with DNA replication. I don’t know which class of species this represents, but there are surely some commonalities in this video with the way DNA is replicated in all life. The videos are just a few minutes long each.
and
https://youtu.be/G1AoVF3k9Hg
The proteins in the video:
Helicase
DNA Polymerase
Primase
DNA ligase
Gyrase
The “-ase” at the end indicates it is an enzyme.
It might be helpful just to watch this video to see the actually mechanics of one of the proteins, namely the polymerase iii enzyme to get an idea of the specificity of every amino acid. It’s only 2 minutes long:
https://youtu.be/ldXXGt8Ihss
DNA Polymerase III is a large molecule composed of polypeptides from several separately translated genes. One of the poly peptides that forms the alpha subunit (the big blob with an alpha on it) is probably on the order of over 1000 amino acids.
Just looking at that system in the video, it’s hard to imagine we can play randomly with 90% of that system and expect it to keep doing it’s job. But even on that generous assumption we can randomize 90% of the 1000 (actually more) amino acids on the alpha subunit, that leaves 100 amino acids that are pretty important.
20^100 is a big number.
NOTES:
refeference to the Uniprot alpha catalytic subunit
Yes, a very long time. It’s a wonder why putting a steak in a bowl of water doesn’t instantly dissolve it. It’s almost as if the spontaneous rate of hydrolysis is actaully very low and the barest of catalysis of peptide bond formation above the uncatalyzed rate will produce proteins faster than hydrolysis can degrade them. Weird right?
Is DNA polymerase critical to life (and did life start with DNA?) or is it possible a smaller polymerase, made entirely of, for example RNA, could exist and be responsible for replication in an earlier and simpler form of life?
Rumraket,
Its a wonder it doesn’t dissolve it instantly? Really?
When creationist can provide any legitimate evidence for a young earth, then you might have a point. Until then, you can’t ignore time.
“peptide bond formation above the uncatalyzed rate”
Huh? In water? Don’t think so.
https://www.researchgate.net/publication/231525176_Rates_of_Uncatalyzed_Peptide_Bond_Hydrolysis_in_Neutral_Solution_and_the_Transition_State_Affinities_of_Proteases
In pre-biotic soup there could be even faster hydrolysis
Thaxton references this book for the high hydrolysis rates:
In any case, time is the enemy, not the friend of evolving proteins in a pre-biotic soup.
A half-life of 600 years at 25°C? That is fast! 🙂 No wonder prokaryotes need to live such frenetic lives to keep ahead.
Hi everyone,
Thank you all for your comments. First, regarding abiogenesis: I’d just like to highlight two brief quotes from Dr. James Tour’s recent talk, “The Origin of Life – An Inside Story,” which indicate the need for intelligent design, without Tour ever using that term (bolding mine – VJT):
Second, I’d like to thank Glen Davidson and Rumraket for their comments on molecular machines. I was interested to read Glen Davidson’s prediction that long proteins would actually be more efficient than shorter ones. I still can’t quite see how that would work, though. Granted, there are many more possibilities with long proteins, but the odds of evolution hitting on an optimal or near-optimal way of performing a biological function are also much lower. Re Glen Davidson’s point about a designer not being constrained by heredity: I’m not so sure. If invention is inherently incremental (as I suggested in my review of Douglas Axe’s book, Undeniable), then heredity may be the best way to go, when designing new proteins to perform new biological functions. The real question I think we need to examine is whether the step-by-step evolution of molecular machines shows any signs of being guided. For instance, did it proceed along an optimally short pathway?
Third, I fully accept Rumraket’s points that molecular machines actually contain not one but a multitude of proteins, and that they didn’t appear holus bolus overnight, but evolved in stages. As I’ve said, I don’t think stepwise evolution is incompatible with design.
Fourth, I think it was very honest of Rumraket to declare (bolding mine):
We need to keep in mind that scientists still don’t know how rare functional proteins are in amino acid sequence space. For all we know, Axe might be right – at least, for 150-aa proteins. And we still don’t know whether there is a series of “stepping stones,” or shorter intermediates leading up to these 150-aa proteins which are found in all living things today. There might well be. But we don’t know that.
Fifth, regarding Tom English’s point on the distinction between sampling and searching, I’m currently learning a little more about COI, and finding out some interesting stuff. I’ll let you know what I’ve learned in a few weeks.
Sixth, I would like to say a big thank you to Sal for his videos on DNA replication at https://youtu.be/s3nDTGg73AU
and
https://youtu.be/G1AoVF3k9Hg .
Seriously, I think it’s very hard to watch them and not come away impressed. These purely factual videos make a very powerful prima facie case for design. I also think Sal makes a telling mathematical point about infinites when he writes: “there may be an infinite number of enzymes possible, but to have enzymes that fit together and work together as critical parts in a chemical replicator makes such replicators improbable.” He could very well be absolutely right on this point. Frustratingly, though, I don’t know any way to prove this mathematically.
Hi Vincent,
Have you read Andreas Wagner’s book Arrival of the Fittest?
From your link: “Natural selection can preserve innovations, but it cannot create them. Nature’s many innovations—some uncannily perfect—call for natural principles that accelerate life’s ability to innovate.”
So, nature has innovations even though it cannot create them. Where did the innovations come from then?
Is this a quote from the book? Why would he say that? Is he an ID-ist?
By the way, can anyone email me a copy of Dr. Rachel Brazil’s recent paper, “The origin of homochirality”? I was able to browse it one night, but the following night, I was denied access. I don’t know what’s going on there. Thanks in anticipation.
Read it again Sal. I said even a low rate of CATALYSIS of peptide bond FORMATION, will put the FORMATION rate of proteins ABOVE the rate of HYDROLYSIS.
You can FORM peptide ponds or you can HYDROLYSE them. These two reactions are in compentition. In pure water, the rate of HYDROLISIS is above the rate of FORMATION.
But if you add a CATALYST of FORMATION, the rate of FORMATION will be above that of HYDROLYSIS, so you will be making peptide bonds FASTER than they HYDROLYSE.
Get it?
A catalyst is something that SPEEDS UP a chemical reaction. Peptide bond formation is a chemical reaction. So is hydrolysis.
So if you have a CATALYST of peptide bond formation, you can make proteins faster than they break down to spontaneous hydrolysis. Unless of course there is also a catalyst of hydrolysis. That is the question then. There are biological catalysts, enzymes, that catalyze both reactions. There are ones that MAKE peptide bonds and there are ones that break them down (hydrolyze them).
Everything you wrote in your response is irrelevant to what I wrote in mine.
Are you familiar with the concept of a metaphor?
I would agree with this.
Even if I encountered what appeared to me to be very clear evidence of divine design in nature, I would be inferring exclusively natural mechanisms for producing this evidence in my scientific work. This is how methodological naturalism works. Also, this is how I understand God sometimes works.
I think Prof. James Tour would do the same as well. He is very skeptical (maybe even convinced it is impossible?) that the first cell could have arisen by biochemical processes. At the same time, he encourages hopeful scientific research to uncover these mechanisms. Most importantly he stops short of insisting that natural mechanisms for abiogenesis do not in fact exist (because scientific ignorance is not a proof of non-existence).
I suppose the real question is, outside of science, what do we think is the origin of the first cell?
I am agnostic here to mechanism, and so are many biologists. I suppose in this realm (outside of science contemplating abiogenesis) worldview does have some impact. Those who believe in God, of course, are more open to the notion that God created the first living cell. Those who do not believe in God, of course, are convinced that natural mechanisms were sufficient.
Who is right? Well, at this point, we are beyond science’s ability (at least in the current moment) to adjudicate.
Here is the underlying scientific study. It is a great read.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857173/
This seems right to me.
Which catalyst did you have in mind regarding the steak in your example, the catalysts that were from living things? 🙄
K. Dose (not an IDist) suggested the pre-biotic soup would actually cause hydrolysis fast in polypeptides (months).
One will see papers on Salt Induced and Clay catalysis, but when one reads the fine print one realizes the amino acids have to be taken out of the water to induce condensation reactions, and they amino acids have to go through cycles of wetting and drying.
https://www.ncbi.nlm.nih.gov/pubmed/10465717
But, with respect to the pre-biotic environment, I suppose Larry Moran would be our best resource on the question of amino acid polypeptide hydrolysis in pre-biotic soups.
Sometimes God works as if God does not exist. 🙂
Why are you blathering about prebiotic soups? Nobody here is suggesting life arose in prebiotic soups. I simply mentioned the point about catalysis because it is silly to talk about uncatalyzed spontaneous rates of chemical reactions as if anyone thinks life arose like that.
In life, the formation of peptide bonds is catalyzed by RNA. But RNA is not the only knows catalyst of peptide bond formation. You want to know another? The a-chiral amino acid Glycine. You have a solution of activated amino acids that contains glycine? Glycine will catalyze formation of peptide bonds between other activated amino acids.
That will get you, among other products, diglycine. Guess what, Diglycine is even better at it than glycine. Curious fact, isn’t it?
You want to know an even better one? GlyGlyGly. The tripeptide of Glycine is a catalyst of peptide bond formation too, and it is slightly better than diglycine.
Now, did life start with Glycine? Probably not. But the point is this: Resist the propensity to think only long and complicated, highly specific biopolymers found in extant life, can do the job of organocatalysis.
This is plain dumb. I was using the steak in water example to show that the idea that hydrolysis is so fast that peptide bond formation in water is impossible, is an absurdity. The point, which apparently you are supernaturally resistant to, is that it takes even a relatively low rate of catalysis of the FORMATION of the peptide bonds, to bring it ABOVE the rate of hydrolysis. Because the rate of hydrolysis is slow, which is why steaks (and fish) don’t dissolve as soon as they come in contact with water.
I’m so sorry I have to make all this clear in tiny digestible fragments for you, I was operating under the seeming misapprehension that you can think for yourself.
Yeah what a curious thing. The invisible and undetectable is practially indistinguishable from the nonexistent.
Sometimes?
Thats the point.
Its too different issues. Geology and biology.
Biology conclusions must be intellectually independent of geology conclusions if the biology only works if the geologuy works.
I noted this in Stephen Goulds book. He admitted that it was geology that established evolutionary biology boundaries.
its everything.
So making evolution as a biology investigation null and void.
Its not the creationist must prove a young earth nor the evolutionist prove a long earth.
its that the evolutionist must prove his evolution is not only proven by geology.
Timelines in time must not taint biology investigation for origins.
This is a major flaw in evolutionism and they will write this in school essays in the future.
I’m working on some of the formalisms. Behe’s approach in edge of evolution represents some of my thinking and I think it is the right direction.
Regarding enzymes, let’s back up a bit and look at the man-made world.
There are various machines that keep time:
Sun Dials
Hour Glasses with sand
mechanical watches
electronic watches
a smart phone
an atomic clock
We can have a variety of ways to implement the same basic task, but some are more refined, and some do more than just keep time (a smart phone) and some are overly complex.
One can imagine a Rube Goldberg clock, and in fact the Nobel Prize winner Aziz Sancar complained that Eukaryotes keep track of circadian rhythms (like sleeping schedules) using Rube Goldberg clocks, and he argued the simpler clocks found in prokaryotes are “intelligent clocks” because of their simplicity — with the insinuation that Rube Goldberg clocks are badly designed. He wrote his paper “Intelligent Clocks and Rube Goldberg Clocks” about 7 years before he got the Nobel Prize.
In contrast to Sancar, ID proponents view Rube Goldberg machines as evidence for design. The Peacock’s tail is a Rube Goldberg design in that it is excessive beyond mere necessity and so extravagant as to be a survival liability for the species. Darwin recognized Peacock tails as evidence against his theory of natural selection, and said the Peacock’s tail made him sick. He came up with a flimsy theory of sexual selection to try to work around it, but his sexual selection theory doesn’t work and it can’t cover all the extravagances of nature that go way beyond mere survival.
How does this relate to enzymes, proteins, and chemical replicators? We can have simple chemical replicators — salt crystals. We can have very complex replicators like life.
We can make several enzymes that catalyze the same reaction, but some can be made more excessively complex than needed. Just like we can build time keeping devices with a few parts, we can build them with hundreds of parts.
I raise this issue because there is an unfortunate focus on trying to say one small enzyme (say a few hundred amino acids) can do the same job a big enzyme (a thousand amino acids). The insinuation being the big enzyme doesn’t need all it’s parts. But this is like saying a Swiss watch doesn’t need all its parts because a sundial can also keep time. Or that a 100-part Swiss watch can keep track of time, therefore a 200-part Swiss watch doesn’t need all 200 of its parts. There is some illogic here in the way some are estimating enzyme or protein complexity.
We wouldn’t estimate the complexity of a digital watch as small by saying, “an hour glass is simple, therefore a digital watch is simple”. But the same sort of non-sequiturs are put forward when one says “this protein can do the job with only 300 amino acids, therefore a protein that does it with 1200 amino acids can’t be that complex, and 900 of amino acids are not necessary.”
As you can see in the video provided on DNA replication (only one of the many tasks of a simple organism), there are a lot of interdependent parts. It doesn’t matter whether chemical replication can happen more simply (like salt crystals), the real problem is why the replication is happening extravagantly.
I showed the Polymerase III enzyme (abbreviation Pol III). Pol III makes no sense if there is no DNA to replicate. Pol III also needs DNA (or some thing just as amazing) to make it. We need Poll III, Gyrase, Helicase, Topisomerase, and who knows how many other “-ases” along with DNA to make the replicator we call life. Sure, we can imagine simpler systems, but the real problem for OOL is why an extravagant one emerged. Why did an atomic clock emerge when a sundial would have sufficed?
Mung:
Fair Witness:
🙂
swamidass, a Christian, writes:
In what is at least a superficial irony, I, an atheist, would do the opposite. I think we should follow the evidence where it leads, and there’s no reason that science can’t handle supernatural hypotheses as long as they are testable.
So I, an atheist, am open to scientific evidence in favor of divine design, and swamidass, a Christian, is not.
I think the irony is really only superficial, however. Given the weakness of the evidence for God, it’s actually beneficial for theists, if they want to justify hanging onto their beliefs, to embrace methodological naturalism. MN enforces Gould’s “non-overlapping magisteria”, boxing science and religion into separate domains. Typical religious beliefs benefit far more by being protected from scientific-style inquiry than science benefits by excluding supernatural hypotheses.
We should be exploiting science’s considerable power wherever it can profitably be applied, not seeking to artificially limit its scope.
Well, so-called “conservation of information” in the context of “no free lunch” for search originated with me in 1996. I’ve learned a little more, and a little more, and a little more for twenty years now. The most unpleasant thing I learned was that I was dead wrong to use the term conservation of information. The sampling process is statistically independent of the sample of values of the objective (fitness) function. Put simply, the process is absolutely uninformed: there is no information to conserve. George Montanez is now applying a model of sampling that is very similar to the one for which I proved statistical independence of the sample selection process and the sample. It takes only a teeny modification of my argument to produce the same result for his model. The upshot is that there’s a good reason (or two or three) that everyone outside the Evolutionary Informatics Lab says that a sample contains data, not information. Even Winston Ewert acknowledged, sometime last year, that “active information” is actually a measure of bias in the sampling distribution, relative to a baseline distribution. But he went on calling it information, because that’s what fits the story the EIL wants to tell.
The reason I’m throwing this comment at you now is that it seems relevant to what you’ve quoted from Tour. He evidently is talking about the difficulty in achieving prespecified objectives in engineering. When we initiate a sampling process for the purpose of turning up one or more solutions to a problem (prespecified), it is we who search, not the sampling process itself. The sampling process is absolutely uninformed of our objective. A separate (logically, at least) component recognizes when the sample contains an object that satisfies our objective.
Evolutionary biologists are not saying that evolution has some magical power for hitting prespecified targets. They’re saying that the vast majority of species that have existed are now extinct. They’re saying that there probably are vastly more folding proteins than evolution has “stumbled upon” (to use a term that Axe did in the video where he explained that evolutionary “search” doesn’t really search). I am saying that biological evolution is vastly more likely to stumble upon something that we regard as wondrous after the fact than to stumble upon something wondrous that we specify in advance.
Here’s a contrived, but helpful example. Consider a process that, at each step in time, has 10 possible ways of continuing, and is as likely to go any one of those 10 ways as any other. The probability of each the 10 possibilities at a given step in time is 1/10. For simplicity (again), let’s say that the outcome of
steps can be reached only in 
steps. Then the probability of the particular outcome realized by the process is exponentially decreasing in time. After 1 step, the probability of the outcome is 
; after 2 steps, the probability of the outcome is 
; … after 
steps, the probability of the outcome is 
The probability of particular outcome after 151 steps is surely 
No matter what argument you make that the actual outcome is somehow wondrous (e.g., it has a detachable specification), it remains the case that there was no miracle at any step. The issue is not how small the product of the probabilities is, but instead how small the individual probabilities are.
The issue in exploration of the space of AA sequences is somewhat similar. The size of the space of possibilities is irrelevant to the adequacy of an evolutionary account. What fraction of the possible sequences correspond to folding proteins is irrelevant to the adequacy of an evolutionary account. What’s relevant is the probabilities of individual transitions that actually have occurred (more accurately, the expected waiting times for the transitions to occur). Note that seemingly improbable transitions became probable when scientists learned about shuffling of protein domains. Scientific discovery is the bane of arguments from improbability, which invariably turn our uncertainty about processes (usually due to inadequate knowledge) into certainty that the physical chance of an event is low. I’ve packed quite a bit into that last sentence. I’m trusting you as a philosopher to give it some serious thought.
What keiths said. Methodological naturalism doesn’t have to exclude the supernatural, in a way it’s misnamed. All you need is a testable hypothesis. Some have been proposed and even tested (prayer studies), others aren’t testable (most ID claims).
P.S.–I neglected to say that each step of the branching process is independent of those that came before.
Would you accept the account of supernatural intervention, or would you insist on looking indefinitely for something unknown in nature? It’s the latter for me, though small p-values in several independent replications of a well designed study would add considerably to my (already considerable) epistemic humility.
Mung,
It is a possibility, but is rejected on the principle of parsimony. More changes would be required to arrive at the pattern we have in the order suggested than in the order generally accepted.
Parsimony is not written in stone – it would be vanishingly unlikely that ALL transitions took the most parsimonious route. But on this particular large-scale example, prokaryotes-to-eukaryotes would be a bet worthy of anyone’s bottom dollar.