On variant genetic codes

Craig Venter has achieved celebrity status in Creationist circles for little more than a slightly embarrassed smile. In a discussion involving, among others, Richard Dawkins, Lawrence Krauss and Paul Davies, Venter makes the eyebrow-raising statement that he does not regard Mycoplasma as the same ‘life-form’ as other prokaryotes, or eukaryotes. His reasoning was that they have ‘different genetic codes’. Dawkins reasonably points out that their codes are ‘all but identical’ (they differ in just one position, Trp for STOP). Creationist videos of the exchange tend to fade on the aforementioned smile given in response. The videos are presented, breathlessly, as “Venter denies Common Descent in front of Richard Dawkins!”. However … one difference? Is that really enough to justify a claim of separate origins? This would be like claiming that Norwegian and Swedish had separate origins on the strength of the difference between æ and ä or ø and ö.

When last I looked, there were about 18 known variant codes. More are being discovered all the time. It’s instructive to compare the differences – but first, I’ll run through the basic mechanics of protein coding from DNA.

The code comprises groups of three DNA bases – triplets. With 4 different bases, there are thus 64 different possible triplets. One DNA strand’s sequence is transcribed to ‘messenger RNA’ (mRNA) using base-pairing affinities. A pairs with T (or U in RNA, simply a methylated T) and C with G so the transcript of ACGT is UGCA. This is a physical interaction and not merely an informatic one – ACGT binds most strongly to its complementary sequence (T/U)GCA. Once the mRNA is formed, possibly after some post-transcriptional editing, it is passed to a ribosome for translation into protein. A pool of up to 64 ‘transfer RNA’ (tRNA) molecules is maintained by up to 20 enzymes called aminoacyl tRNA synthetases – aaRSs. The aaRSs are the main Keepers of the Code. Each different aaRS will charge one or more of the different tRNAs with a specific amino acid. The acid is attached to a specific sequence – ACC – at one end of the tRNA. At the other end lies an ‘anticodon’ – a triplet with the same sequence as the original DNA triplet, which has the strongest binding affinity for the complementary sequence present in the transcribed mRNA – the ‘codon’. Charged tRNAs are like paint brushes with a dab of colour on one end and a unique shape on the other. Given a template to line them up and dock the appropriate shapes, dabbing the other ends on a growing string, the same pattern can be produced repeatedly and mechanically.

Translation commences at a ‘Start’ codon – typically, though not universally, corresponding to the amino acid methionine, codon AUG. Given that binding is most strong between a codon and its anticodon, each exposed mRNA triplet has the greatest affinity for just one tRNA. The relevant tRNA docks and the peptide is elongated with the amino acid at its other end. Translation ceases when no tRNA can be found corresponding to a given codon. Such codons – those without tRNAs – are termed STOP codons. Typically, this tends to be more than just a simple passive mechanism – the growing peptide does not merely ‘fall off’ the ribosome for want of an acid, but release factors are triggered, which break the bond between the synthesised peptide chain and the tRNA to which the last acid was attached.

The mechanism described above is universal – all organisms on earth synthesise their proteins in the same way. That alone should cause Venter to hesitate in his dubious assertions regarding ‘life forms’ of separate origin. If everything on earth shares the same system, it really does not indicate that they had separate origins, however much difference in detail. Venter argues elsewhere that sequence data starts to lose sight of a simple tree in deep time, and this is true to some extent, due to such factors as horizontal gene transfer – genes passed among organisms rather than inherited from common ancestors. Yet the very fact that gene transfer is even possible indicates that transfers are between relatives. The kind of things that might more securely indicate separate origins are, for example, L-sugars giving oppositely-coiled DNA, or D-amino acids, or acids other than the canonical 20, or base pairs other than the standard 2. What one would not expect is to be able to pass a ‘well-formed string’ from one organism to another of completely separate origin, yet have an equally well-formed string emerge after processing in a truly foreign system. This is like Jeff Goldblum uploading a virus to the alien computer from an Apple Mac in Independence Day – pure hokum.

Another aspect to consider is the structure of the aaRSs that determine the code. The 20 acids divide neatly between Class l and Class ll enzymes, based on their reaction chemistry and direction of approach to the substrate. Class l enzymes attach the amino acid to the 2′ -OH of the substrate; all but one Class ll enzymes attach to the 3′ -OH. Either way, the acid migrates to the 3′ before the ribosome gets hold of it, so there is no effective difference. Every enzyme in each class bears a sequence relationship to all other enzymes in that class – but there is no such relationship between the classes. It appears from this data that aaRSs arose at least twice, and also that the modern code of 20 acids most likely arose from a much smaller set, by duplication. All of this activity would have to have preceded LUCA, our last common ancestor, because the various quirks noted above are common to all life. How can that be? OK, one might say ‘design’ – a catch-all that can be invoked to explain all data – but that’s not what Venter thinks, so it’s not clear what explanation he would have for that massive commonality of mechanism and structure, if not genetic common origin.  

But of course – as Dawkins pointed out – it’s not merely the common details of mechanism, but the code itself that speaks loudly of a single surviving origin. The commonest code is termed the ‘standard’ code. This is used in most eukaryotic nuclei, most bacteria and archaea, and plant plastids. On the principle of parsimony, this is most likely the code used by LUCA itself. It has 3 STOP codons – UAA, UAG, UGA – and usually – not always – starts with methionine. In Mycoplasma, UGA codes for tryptophan, which is coded solely by its close neighbour UGG in the ‘standard’ code. This is actually a very common substitution – the codes of nearly all mitochondria do exactly the same at this position, for example. Thus, Venter is effectively saying that our own mitochondria are not the same ‘life-form’ as our nuclei – a perverse notion, since many mitochondrial genes have migrated to the nucleus, and are synthesised there before re-export. He is saying, by implication, that the difficulties we would have synthesising Mycoplasma proteins, or vice versa, preclude gene migration from the mitochondrion, unless that migration preceded the amendment to the mitochondrial code. That’s a strong claim, even if made unknowingly.  

But how can the genetic code change – how could we possibly have common descent of all codes? There are 3 principal possibilities for a code change

  1. Substitution of a STOP by an acid
  2. Acid-for-acid substitution.
  3. Substitution of an acid by a STOP

I have ranked them thus in order of assumed constraint against them.

  • If a STOP is substituted by an acid, it will have the effect of adding a small ‘tail’ to those proteins having that STOP, leaving the core untouched, which is less likely to be damaging.
  • If one acid is substituted by another, this may well affect the core of many proteins, which will have more impact, but the effect is mitigated if the codon is of low usage, or the substitution is for one of similar chemical property.
  • The third is probably rare – it would have the effect of chopping proteins into short segments, depending on the stochastic occurrence of the relevant codon. Nonetheless, in short genomes with biases against certain codons or base pairs, it may occur with some frequency.  

Now, the Mycoplasma/mitochondrial distinction is of the first type – the assumed ancestral code has apparently been amended by addition of UGA to the substrates accessible to tryptophanyl tRNA synthetase (an aaRS), which is specific to UGG in our nuclei, but UGA/UGG in mitochondria. A and G are both purines, by contrast with the pyrimidines U, C and T. The first are distinguished by a double ring structure, the second are single, and so they present quite different profiles to enzymes, more easily distinguished than the separate bases comprising each class. In this case, it would require a loss of distinction between the purines, rather than a gain of specificity. Nonetheless, it is very common within the code to see a grouping made simply on the basis of whether the base is a purine or a pyrimidine, rather than at the level of individual monomer, so there is nothing exceptional about this particular substitution.

The supposition that filling in of STOP is the likeliest amendment is borne out by analysis of the genetic codes of extant organisms. It appears that the wholesale replacement of one acid by another has hardly occurred at all since the common ancestor; almost all variant sites function as STOP in one or more variant codes. Of the mere 13 codons that vary in one species or another, 7 are a STOP in at least one. If we ignore the 4 codons restricted to yeast mitochondria in which the entire CUx group has seen a substitution of Threonine for Leucine, it becomes 7 out of 9, which is striking. There is a viable mechanistic reason for this, relating to the relatively mild effect of this particular substitution on existing proteins.

This is possibly the means by which the code itself arose – initially only a small amount of the 64-codon matrix was covered by assignments, as suggested by the apparent coalescence of the 2×10 Class l and Class ll aaRS enzymes upon fewer ancestral enzymes. In such a system, consisting of ‘mostly STOPs’, the extra tail added by assignment of a STOP would be quite short – as STOPs become fewer, the length of the average tail will increase, but in early evolution the constraint against this substitution would be less severe. Gradually, as the codon matrix becomes filled in and proteins become more widely used and longer, the code ‘freezes’, since non-deleterious substitutions become progressively harder and so less frequent.

Any acid-for-acid substitutions that divided a codon group, either due to purine/pyrimidine specificity, or individual base distinction, would tend to favour chemically conservative substitutions. This would generate the much-vaunted fault tolerance of the code – translation errors frequently result in a viable product due to chemically related neighbourhoods in the code. On this model, there is no need to use design or positive selection to achieve favourable arrangements; they are a by-product of the constraint on wholesale substitution, which favours property conservation in a genome-wide manner. 

Gradual filling in of STOPs would thus have led to both a richer code, biased towards construction of chemically conservative neighbourhoods, and incidentally to a gradual lengthening of proteins, amending both the v and the n of the assumed v^n ‘search space’ in which some imagine proteins must arise fully formed in a single bound.

And so, having reached more-or-less its present form in the population of which LUCA formed a part, descendants such as Mycoplasma and us sprang forth – with minor variations.

Edit to add – my spreadsheet of the up to date codes table. A code 32 was added just in the last day or so – although, pace J-mac, there are not 32 codes, but around 25, due to mergers. It is not always a straightforward issue to determine whether a code should be considered truly ‘different’ or not. For example, the GUG start codon is occasionally used in our own cells, but comes up as a difference when used in other codes because it is not annotated as part of the ‘standard’ code. And ciliates are just plain bizarre!

The sheet is colour coded to highlight the differences – red for assignment variants from the standard code, and yellow for Start/Stop differences.

145 thoughts on “On variant genetic codes

  1. Paul A Nelson,

    If any two codes differ in the use of a STOP here or there, this does not entitle one to dismiss the entirety of the rest of the code as somehow an irrelevance. Clearly, despite variations, the code supports a common origin. If one or two commentators took a strong position – we will NEVER find variants – then obviously they would have to row back on that in the light of data, as all good scientists do.

    If you think the differences are sufficient to completely disbar a common origin, I’d say you (and Venter) are going far further than the data merits. The pattern is clear: variants cluster around Stops. The same few codons tend to be hit by these variations. Why? I have given a plausible mechanistic explanation of this pattern above. What is your alternative?

  2. Alan Fox: Lovely guy. I had quite a bit of contact with him back in 2005 (mainly to do with his being a reviewer of Behe’s Darwin’s Black Box) during the build-up to the Dover trial. I recall he was sceptical of “RNA World” as a scenario for OOL. He recommended his book Planetary Dreams as a good exposition of his current (2005) views and I still have it. I’ll have a look to remind me. I do recall him mentioning he was agnostic and certainly not a supporter of “Intelligent Design”.

    I remember when Robert Shapiro was called Dr. No lol …thanks to his 99.9% rejection rate of nonsense papers on OOL in his peer-review process… He is also one of my personal heroes… 🙂

  3. Allan Miller: If any two codes differ in the use of a STOP here or there, this does not entitle one to dismiss the entirety of the rest of the code as somehow an irrelevance.

    Try to apply Venter’s experimental experience with the genetic code being an
    operating system…You will make sense of the two different spellings of the word center vs centre but not a computer operating system…
    Venter digitized biology and realized that the deviations in stop codons are lethal to the simplest of the organisms…

  4. Paul A Nelson:
    The other issue will require me to do some more digging, but right now, AFAIK, every experimental modification of the code has required investigators to “help” the cells over the fitness valley entailed by the coding change.For instance, investigators supply the wild-type tRNA on a plasmid during the transitional period.Otherwise the cells die.

    This is surely significant, in relation to claims made above that the evolution of the code should be easy to accomplish by undirected evolutionary processes.

    How easy is easy? We have a modification that clearly occurs infrequently – the standard code is used by almost all eukaryotic nuclei and prokaryotes. There is probably strong negative selection against. Most variants occur in mitochondria, which have small genomes and complementation from nuclear genes. It probably also requires a codon usage threshold at the tail of stochastic variation, which may occur but rarely.

    The expectation that this should happen almost daily if it happens at all seems a tad misplaced.

  5. Paul A Nelson:
    Gregory,
    Hi Gregory — of course I remember you.

    “Naturalistic” and “natural” as I’ve used them here mean simply “no intelligence causally implicated.” I take intelligence as a kind of cause to exhibit distinct (or diagnostic) features, such as planning, choice, actualization of abstract entities, etc.

    Ok Paul. Good. Then it’s easier to be generously polite with you.

    Over at PS, Joshua booted me in defense of his ideology just as you arrived, on a thread about ‘methodological naturalism,’ which the guy simply can’t seem to allow himself to understand. I would have reached out to you there if not. This place is obviously less savory in its largely anti-religious ‘skepticism’, though it’s not hindered by the censorship of other places on the internet involved in the creation, evolution, Intelligent Design conversation.

    As a non-biologist I have almost nothing to say on the topic of this thread, however, since you responded above, let me just clarify, because you are trained as a philosopher (of biology) at the University of Chicago, so being careful with language is something you undoubtedly value. I won’t divert here after this, just to note what follows, which could be picked up on another thread if there is interest.

    Something can be ‘natural’ and a person can speak about & even study the ‘natural’ world without embracing ideological naturalism. Thus, if for you ‘naturalistic’ & ‘natural’ are used equivocally, then we have a problem. I believe those 2 terms contain related, but significantly different meanings.

    The notion of ‘natural intelligence’ would also be difficult to place comfortably in your current schema. At the same time, divorcing ‘natural’ from ‘intelligence’ just isn’t going to fly with most people.

    The intelligence you speak of re: planning, choice, etc. are just not topics studied in the major fields of *any* of the main IDists: Meyer, Dembski, Behe, Denton, Wells, Axe, Gauger. It’s just the few humanists among your ranks who are actually trained to study ‘planning’ & ‘choice’ & do it continually & on-going, & unfortunately they studied history, literature & government, rather than psychology (don’t count Bill please), sociology, economics or anthropology.

    ‘Planning’ & ‘choice’ are terms studied properly, often, regularly, repeatedly, and perhaps most importantly, *without major controversy*, across a range of fields in universities today. Since you won’t deny this, I’m sure it means you understand the frustration some of us have with the way Meyer, West & co. at the DI have framed this ‘conversation’ (their monologue) and realise why they’ve lost credibility by avoiding what everyone else sees clearly & without any doubt. By protecting themselves from criticism by religious believers & scientists such as Owen Gingerich, Steve Barr, Michael Heller, they have given the whole game away. You have been one to joke about these things in hindsight, so perhaps you’ll offer a helpful & humble voice updating yourself here, as likely you’ve moved beyond YECism by now also.

    As for me, I distinguish natural-physical sciences from human-social sciences. If you’d like to include the humanities, then put the two together for more coherence: SSH. But to try to divide ‘intelligence’ the way you, Philip Johnson, even guys like Jonathan Witt are trying to do, seems outright devious, not graceful, but forced. It’s a largely semantic argument that continues to peddle a misnomer, feeding on people who simply don’t know any better & are looking to folks like you for leadership.

    I don’t understand why you equivocate between ‘naturalism’ & ‘natural.’ It makes no sense to me & isn’t needed for religious people today. It just seems unnecessarily divisive to lump the terms together.

  6. Hi Allan,

    I hope you didn’t miss what I said above: “I think it is entirely possible that observed variant codes derived from a once-universal code by some unknown natural pathways.” My interest in variant codes — aside from their intrinsic biological curiosity, which is considerable — stems, rather, from the role these observations play in discussions about what universal common descent (UCD) tells us about the world. For several years, with my Discovery Institute summer seminar students, I’ve used the discovery of variant codes as a case study in how UCD makes predictions and relates to the other parts of our biological knowledge.

    But I wouldn’t rest a case for multiple origins on the genetic code variants. The “universal” code has too many features which look fine-tuned. Nor would Venter, from what I know of his thinking. If you read the 2007 roundtable, his main line of evidence for multiple starting points is the unexpected genetic diversity he found while sampling environmental DNA from sea water during his two-year voyage around the world in a yacht.

    Genetic code evolution scenarios tend to be complicated stories, with many key episodes it is easy to overlook. This is true even for the apparently low-risk transitions, such as those reassigning stops. I wish I had more time today to go into details, but I’ve already broken my self-imposed rule about not getting mixed up too often in internet discussions. I am sorry. This topic (genetic code evolution) is incredibly interesting, as you well know.

  7. Gregory,

    Your intelligence is, in one sense, perfectly natural. There you are, at your computer, and here I am at mine — two natural objects typing out messages.

    Yet no physical regularity, or set of physical regularities, would allow anyone to predict the character strings we produce. Much better outcomes (in re prediction) would follow from (1) knowing something about Gregory, (2) knowing something about Paul, (3) knowing something about the ID debate and its history, and so on. In other words, knowing something about particular agents — not physical laws or processes.

    I don’t have any problems with saying that intelligence is “natural.” I do think reasoning goes badly haywire, however, when “natural” is ALSO supposed to mean “derived bottom-up from physical entities and processes, with no analytical remainder once physics has done its job.” See Alex Rosenberg, Sean Carroll (the physicist, not the biologist), Sam Harris, et al, for further explication.

    Gotta run.

  8. J-Mac: Try to apply Venter’s experimental experience with the genetic code being an
    operating system…You will make sense of the two different spellings of the word center vs centre but not a computer operating system…
    Venter digitized biology and realized that the deviations in stop codons are lethal to the simplest of the organisms…

    Analogising DNA with computer code is misleading. I know a fair bit about both; they have markedly different degrees of freedom.

    As I noted above, there is a considerable difference between strong selection against – which is not in dispute – and something being impossible. Clearly, because there aren’t millions of variant codes, and there is a significant pattern in those variants that do exist, we can be sure that it isn’t easy or frequent. But then, we don’t have to explain a frequent change, simply a rare one.

  9. Paul A Nelson:
    Hi Allan,

    I hope you didn’t miss what I said above: “I think it is entirely possible that observed variant codes derived from a once-universal code by some unknown natural pathways.”

    I’m afraid I did, initially.

    Venter’s case rather founders upon the strong signal of commonality. Rumraket linked above Koonin’s analysis, where the tree signal remains clear despite HGT. And when 63 out of 64 codons don’t vary, I find it hard to get worked up about the one that does.

    There is a frequent confusion between sequence data and the code itself. The sequence tree has tangled roots because of HGT. But the code ‘tree’ still points to a seed. HGT is only possible because the code is – to borrow Dawkins’s qualification – ‘all but’ universal. But within the code itself we also have sequence data – the aaRS enzymes apparently coalesce upon two separate common ancestor sequences, one Class l and one Class ll. Subsequent sequence evolution has been muddied by HGT – not least of the aaRSs themselves, because such enzymes are readily transferable. There does not need to be a squid way to aminoacylate a tRNA, and a bacterial way, and an algal way. But if the codes were different – if the origins were different – such transfers could not occur. Not only would the translated protein be all wrong, but even if right by some fluke its action would be inappropriate for the cell it wound up in.

  10. phoodoo: Optionality?I can’t tell if this is one of those times when you are using teleological logic because its convenient, and you actually mean something else?

    I’d hope you were familiar enough with my views to recognise that I would never mean ‘something else’, if that something else were foresight, plan or intent. When I say ‘optional’, I simply mean that these codons vary – they are not as inflexible*** as the invariant codons.

    ***No, I don’t mean they are more bendy.

    Again, are we using convenient language that we really don’t mean?Is there context in the genome?

    Yes. A particular sequence may sit inside an intron, an exon, a control region, a UTR, an intergenic sequence, a centromere etc, and may have different effects depending on whether it is towards the beginning, middle or end thereof. The term came direct from the piece I linked, but effectively it means that a codon is treated as an amino acid when in the middle of the mRNA, but as a STOP nearer the end. It’s actually due to proximity to the UTR – the untranslated region that sits beyond the exons. I’d say that was context dependence, without expecting a fight about it.

    I believe evolutionary theory would be so much clearer if writers wrote what they meant, instead of always utilizing some vague analogies.

    I actually argue against overuse of analogy – Charlie’s fluffy notions, the genome as a computer program … urgh. I don’t think the problem lies entirely with us, vis a vis communication with you. Your default position is that we are perpetually trying to pull a fast one.

  11. I’ve uploaded my spreadsheet of all codes, if anyone wishes to have a graphic of the patterns in variants. The original data came from here.

    It’s colour coded, red for assignment differences from ‘standard’ and yellow for the start/stop variation on the following line. Incidentally, even when an alternate start codon is used, the commencing amino acid is usually methionine, not the acid normally coded for by that codon. It’s … uh … context dependent.

    Contrary to J-mac’s scurrilous and baseless accusation, this was the table I used for my analysis (except for no. 32, which only just arrived in the last day or so), and it has 25 codes, despite being numbered to 32. Some of them are debatable though. 11, for example, is a composite, because different initiation codons have been noted in different bacteria. No one strain uses the whole code. And apart from extra Starts, it’s no different from ‘standard’ – indeed some of these initiation codons are themselves used in our own cells, despite coming up as differences because they happen not to be regarded as part of the ‘standard’ code. Lumpers and splitters…

    The same goes for ciliates, which have a far more complex pattern than shown here, albeit with the same codons tending to be hit, and always associated with STOPs.

  12. J-Mac: There is much, much more to Venter’s denying common descent…

    He doesn’t deny common descent. I have only ever seen Craig venter be unclear, I have never seen him actually deny common descent. Not that it really matters, because then he’d just be wrong.

    Here he is affirming common descent to none other than Richard Dawkins, on the basis of the genetic code: https://youtu.be/3E25jgPgmzk?t=525

  13. Allan Miller: Analogising DNA with computer code is misleading. I know a fair bit about both; they have markedly different degrees of freedom.

    It’s not misleading! The opposite is actually true because you are stuck in the dark ages of Darwinosauria…
    Have you heard of the term biological teleportation?

    I bet you haven’t…
    https://singularityhub.com/2017/06/28/biological-teleportation-gets-closer-thanks-to-craig-venters-digital-to-biological-converter/#sm.0001m1tkou1421fgwyuefw1g9b72f

  14. Allan Miller: Contrary to J-mac’s scurrilous and baseless accusation, this was the table I used for my analysis (except for no. 32, which only just arrived in the last day or so), and it has 25 codes, despite being numbered to 32. Some of them are debatable though. 11, for example, is a composite, because different initiation codons have been noted in different bacteria. No one strain uses the whole code. And apart from extra Starts, it’s no different from ‘standard’ – indeed some of these initiation codons are themselves used in our own cells, despite coming up as differences because they happen not to be regarded as part of the ‘standard’ code. Lumpers and splitters…

    The same goes for ciliates, which have a far more complex pattern than shown here, albeit with the same codons tending to be hit, and always associated with STOPs.

    lol

    The so-called universal code and now with its many variations, it is a double-edge-sword…as already mentioned earlier, including by Paul Nelson…

    Has the genetic code (triplets) appeared as such (frozen) in the history of life or had it evolved from a simpler life form (doublets)? What’s the evidence for either scenario?
    If the current code (triplets) evolved from doublets, where are the life forms that still use the doublets? With suspected trillions of microbes on the earth and millions of genomes already sequenced, there has gotta be one species that uses a doublet code… or at least some precursor of it right? Otherwise… you know those skeptics…like Venter and all… They don’t like speculations being experimental scientists with great intuitions… 😉

    Let hear the speculation now….

  15. J-Mac,

    I doubt any extant organisms use a doublet code. In fact, on stereochemical grounds, I think contact between tRNA and codon has always been by a 3 base stretch, so they probably never did read in twos. You can’t bend the RNA tightly enough to reduce the contact area in a tight bend, and you may not get enough energy with 2 base binding to form the peptide bond. As it is, the bases aren’t in a dead straight line, which is why you get 3rd base ‘wobble’ and 4-fold degeneracy, but I’m not convinced you can bend it any tighter.

    Earlier codes may well have only had singlet or doublet recognition, which is still the case for several codon groups in the present code, but I think tRNAs nonetheless made triplet contact.

    Doesn’t really matter for present purposes. The variant codes are variant triplet codes, so clearly LUCA tripped in triplets (prog rock reference).

    And why the perpetual argument from authority? Don’t you have anything to say on your own account, instead of hiding behind Venter’s lab coat? Do you agree with him on everything?

  16. J-Mac: It’s not misleading!

    Evidently, it is misleading, given that we know of a number of people who have been misled.

    Separately, it is unclear to me what you mean by a ‘doublet’ code. If you mean that the protein synthesis machinery only translocated two nucleotides for every amino acid incorporated, then I am quite confident that you are wrong, for the reasons Allan explained to you. If you mean that there was once 100% degeneracy at the wobble position, then what’s the problem? I think that’s pretty likely myself.

    Finally, Venter is a smart guy, but he is also (like Dawkins) something of a narcissistic windbag, IMO.

  17. DNA_Jock: Separately, it is unclear to me what you mean by a ‘doublet’ code.

    Pardon?! I have been under the impression you have been to a lab, no?

  18. Allan Miller: doubt any extant organisms use a doublet code. I

    So do I! So does Venter… Not only that, I will make a prediction that no organism, including some 35 trillion microbe species predicted by microbiologists lately will use anything but triplets… There will be more code variants discovered, we both know that, but not doublets.. It makes no sense from many aspects of life-systems but mainly from quantum mechanics prospective…
    So, that’s why I’m willing to make the predictions…

  19. DNA_Jock: That’s right!
    I even hold patents on codon optimization!
    And, I am still unclear on what you mean by a ‘doublet code’.
    Perhaps you could clarify, choosing between the two alternative meanings I outlined?

    What?! What are you doing here talking nonsense with me??? Shouldn’t you be like Venter living his dream in the lab? Playing god?
    I have a hard time believing it .. but I have been wronged before… many… many times…

  20. A better example of being misled by the relationship of computing and biology would be hard to find. In this case it’s not just poor analogy, it’s the total lack of sensible connection. J-mac would have it that the genetic code is not like language, but is like an operating system, with commensurately reduced degrees of freedom. Why? Because at some point in the future we may be able to digitise organisms… which makes no sense as an argument. I mean, if things-we-can digitise must have the same degree of freedom as the-thing-doing-the-digitising, how come I can get away with speling misteaks in this digitised comment?

  21. Allan Miller:
    A better example of being misled by the relationship of computing and biology would be hard to find. In this case it’s not just poor analogy, it’s the total lack of sensible connection. J-mac would have it that the genetic code is not like language, but is like an operating system, with commensurately reduced degrees of freedom. Why? Because at some point in the future we may be able to digitise organisms… which makes no sense as an argument. I mean, if things-we-can digitise must have the same degree of freedom as the-thing-doing-the-digitising, how come I can get away with speling misteaks in this digitised comment?

    There is only ONE THING that Venter can’t do now out of all the biological teleportations he thought he could do today…Can you guess what?

    BTW: You are making me cry with your pointless comments… you boring you…

    https://getyarn.io/yarn-clip/89fe89a1-a6be-4aec-b05a-56b37bf6a2cf

  22. Allan Miller: A better example of being misled by the relationship of computing and biology would be hard to find. In this case it’s not just poor analogy, it’s the total lack of sensible connection. J-mac would have it that the genetic code is not like language, but is like an operating system, with commensurately reduced degrees of freedom. Why? Because at some point in the future we may be able to digitise organisms… which makes no sense as an argument. I mean, if things-we-can digitise must have the same degree of freedom as the-thing-doing-the-digitising, how come I can get away with speling misteaks in this digitised comment?

    I can’t even be bothered reading half the nonsense he spews. He just rants and drones on about quantum gobbledygook and whatever quasi-scientific-sounding nonsense comes to his mind. With lots and lots of ellipses sprayed all over the place.

  23. Mung:
    Sent a post to Guano.

    Please provide the needed medications.

    There is no medication that can cure or treat Darwinosauria… It not a disease…It is a deliberate, premediated mental blindness..
    No shrink can work with this ….

  24. Allan, thank you for your OP. Perhaps you could get it published in a letters section of some journal. It exhibits thoughtfulness and research. In particular I enjoyed how you anticipated certain responses.

    Is there any reason, any logic, underlying the pattern you believe exists?

    Random mutation, perhaps?

  25. J-Mac: There is only ONE THING that Venter can’t do now out of all the biological teleportations he thought he could do today…Can you guess what?

    No.

    Of course, it would be pointless giving something degrees of freedom when you need to transfer it accurately down the line. However, that constraint does not mean that the things themselves are therefore unchangeable. That would be silly. It would mean there was no possibility of alphabet variance, for example, constrained by its possible future digitised transmission.

  26. Mung:
    Allan, thank you for your OP. Perhaps you could get it published in a letters section of some journal. It exhibits thoughtfulness and research. In particular I enjoyed how you anticipated certain responses.

    Thanks! Still didn’t anticipate the Transmission Constraint though…!

    Is there any reason, any logic, underlying the pattern you believe exists?

    Random mutation, perhaps?

    Hmmm. No, that wouldn’t really be an explanation. It would be like saying ‘quantum physics’. 😀

    I think the code arose in RNA organisms. I think that, initially, docking against an mRNA template was done for energetic reasons – a significant fraction of the energy of formation of the peptide bond comes from the binding energy of the triplet interaction. Most triplets would have functioned as STOP, because they had no corresponding tRNA. Early aaRSs (or their equivalent, pre-protein enzymes) would not be highly specific, but then there would not be many tRNAs so they wouldn’t need to be.

    The story (yes, I know) would then be one of gene duplication, both of tRNAs and of aaRSs, with a corresponding increase in their specificity, distinguishing at first- and third-base positions, first by purine/pyrimidine and then (in some cases) split within those classes down to individual base. When proteins were few and short, substitution would be under less constraint, but always there would be a tendency to favour filling in STOPs over substitution, and chemically conservative subdivision over its opposite. Against the detrimental effect of changes, we could offset the increase in subtlety of the mutations available to individual proteins. But this is limited. The richer the amino acid and protein repertoires become, the less advantage there is in further extension, and the more penalty is attached to code change. It freezes, gradually.

    And this, I think, is a viable explanation of the pattern – several instances of each broad amino acid type, arranged in such a manner that misreads are often silent, and with a preponderance of fourfold (3rd base irrelevant) and twofold (3rd base purine or pyrimidine) redundancy. It also accounts for the sequence relationships among the aaRSs, and the tendency of modern variants to cluster around STOPs.

  27. Mung:
    Allan, thank you for your OP. Perhaps you could get it published in a letters section of some journal. It exhibits thoughtfulness and research. In particular I enjoyed how you anticipated certain responses.

    Is there any reason, any logic, underlying the pattern you believe exists?

    Random mutation, perhaps?

    I agree!
    I lot has changed in the world of the genetic code evolution since Koonin published his paper on the theme in 2009.

    Origin and evolution of the genetic code: the universal enigma

    Eugene V. Koonin and Artem S. Novozhilov

    Abstract

    The genetic code is nearly universal, and the arrangement of the codons in the standard codon table is highly non-random. The three main concepts on the origin and evolution of the code are the stereochemical theory, according to which codon assignments are dictated by physico-chemical affinity between amino acids and the cognate codons (anticodons); the coevolution theory, which posits that the code structure coevolved with amino acid biosynthesis pathways; and the error minimization theory under which selection to minimize the adverse effect of point mutations and translation errors was the principal factor of the code’s evolution. These theories are not mutually exclusive and are also compatible with the frozen accident hypothesis, i.e., the notion that the standard code might have no special properties but was fixed simply because all extant life forms share a common ancestor, with subsequent changes to the code, mostly, precluded by the deleterious effect of codon reassignment. Mathematical analysis of the structure and possible evolutionary trajectories of the code shows that it is highly robust to translational misreading but there are numerous more robust codes, so the standard code potentially could evolve from a random code via a short sequence of codon series reassignments. Thus, much of the evolution that led to the standard code could be a combination of frozen accident with selection for error minimization although contributions from coevolution of the code with metabolic pathways and weak affinities between amino acids and nucleotide triplets cannot be ruled out. However, such scenarios for the code evolution are based on formal schemes whose relevance to the actual primordial evolution is uncertain. A real understanding of the code origin and evolution is likely to be attainable only in conjunction with a credible scenario for the evolution of the coding principle itself and the translation system.
    Introduction
    Shortly after the genetic code of Escherichia coli was deciphered (1), it was recognized that this particular mapping of 64 codons to 20 amino acids and two punctuation marks (start and stop signals) is shared, with relatively minor modifications, by all known life forms on earth (2, 3). Even a perfunctory inspection of the standard genetic code table (Fig. 1) shows that the arrangement of amino acid assignments is manifestly non-random (4–7). Generally, related codons (i.e., the codons that differ by only one nucleotide) tend to code for either the same or two related amino acids, i.e., amino acids that are physico-chemically similar (although there are no unambiguous criteria to define physicochemical similarity). The fundamental question is how these regularities of the standard code came into being, considering that there are more than 10 ^ 84 possible alternative code tables if each of the 20 amino acids and the stop signal are to be assigned to at least one codon. More specifically, the question is, what kind of interplay of chemical constraints, historical accidents, and evolutionary forces could have produced the standard amino acid assignment, which displays many remarkable properties….

    …Before closing this discussion, it makes sense to ask: do the analyses described here, focused on the properties and evolution of the code per se, have the potential to actually solve the enigma of the code’s origin? It appears that such potential is problematic because, out of necessity, to make the problems they address tractable, all studies of the code evolution are performed in formalized and, more or less, artificial settings (be it modeling under a defined set of code transformation or aptamer selection experiments) the relevance of which to the reality of primordial evolution is dubious at best. The hypothesis on the causal connection between the universality of the code and the collective character of primordial evolution characterized by extensive genetic exchange between ensembles of replicators (118) is attractive and appears conceptually important because it takes the study of code evolution from being a purely formal exercise into a broader and more biologically meaningful context. Nevertheless, this proposal, even if quite plausible, is only one facet of a much more general and difficult problem, perhaps, the most formidable problem of all evolutionary biology. Indeed, it stands to reason that any scenario of the code origin and evolution will remain vacuous if not combined with understanding of the origin of the coding principle itself and the translation system that embodies it. At the heart of this problem is a dreary vicious circle: what would be the selective force behind the evolution of the extremely complex translation system before there were functional proteins? And, of course, there could be no proteins without a sufficiently effective translation system. A variety of hypotheses have been proposed in attempts to break the circle (see (132–135) and references therein) but so far none of these seems to be sufficiently coherent or enjoys sufficient support to claim the status of a real theory
    (Excuse me??? What translation system??? Another irreducibly complex systems? Chicken and egg paradox??? Catch 22???) Mike Behe?!!! Where is it in your book???! )

    It seems that detailed modeling of the code evolution from simpler predecessors such as doublet codes (DNA_Jock) could offer some new windows into the early stages of the evolution of coding (72). Notably, backtracking the standard code to the most likely doublet versions yields codes with an exceptional, nearly maximum error minimization capacity (ASN and EVK, unpublished), an observation that moves selection for error minimization and/or frozen accident at least one step closer to the actual origin of translation. Nevertheless, these and other theoretical approaches lack the ability to take the reconstruction of the evolutionary past beyond the complexity threshold that is required to yield functional proteins, and we must admit that concrete ways to cross that horizon are not currently known.
    On the experimental front, findings on the catalytic capabilities of selected ribozymes are impressive (136). In particular, highly efficient self-aminoacylating ribozymes and ribozymes that catalyze the peptidyltransferase reaction have been obtained (137, 138). Moreover, ribozymes whose catalytic activity is stimulated by peptides have been selected (139), hinting at the possible origins of the RNA-protein connection (133). Nevertheless, in a close analogy to the situation with theoretical approaches, we are unaware of any experiments that would have the potential to actually reconstruct the origin of coding, not even at the stage of serious planning.
    Summarizing the state of the art in the study of the code evolution, we cannot escape considerable skepticism. It seems that the two-pronged fundamental question: “why is the genetic code the way it is and how did it come to be?”, that was asked over 50 years ago, at the dawn of molecular biology, might remain pertinent even in another 50 years. Our consolation is that we cannot think of a more fundamental problem in biology.

    Skepticism??? What skepticism? Alan Miller has done such a great job speculationg about the evolution of code variants that even theistic evoutionists/IDs fell for it…

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3293468/#idm140137646989536title

  28. J-Mac,

    Skepticism??? What skepticism? Alan Miller has done such a great job speculationg about the evolution of code variants that even theistic evoutionists/IDs fell for it…

    Do you have any words of your own in response to my ‘speculations’? In what way is my scenario implausible? Is there anything I left out? Have I made an unwarranted leap of logic somewhere? Be specific.

    eta – I’m interested to note that my speculations don’t really fit into Koonin’s three categories.

  29. Allan Miller:
    ,

    Do you have any words of your own in response to my ‘speculations’? In what way is my scenario implausible? Is there anything I left out? Have I made an unwarranted leap of logic somewhere? Be specific.

    eta – I’m interested to note that my speculations don’t really fit into Koonin’s three categories.

    I do…however whenever I offer my own responses, they are not welcomed… Whenever I offer the response based on authorities in science, such as Koonin, Venter, Dawkins, they not welcomed either…

    It seems that the only authority for you is you… In other words, further arguments are pointelss, unless I agree with based on your speculation…I have no reason to even read your further comments because you attempt to support an ideology with your biased point of view and not a shred of scientific evidence…You are not interested in anything but what you chose to believe…

    BTW: It was a set up: for you and the Disgraceful Science guy 😉

    On the origin of the translation system and the genetic code in the RNA world by means of natural selection, exaptation, and subfunctionalization.

    Wolf YI1, Koonin EV.

    Abstract

    BACKGROUND:

    The origin of the translation system is, arguably, the central and the hardest problem in the study of the origin of life, and one of the hardest in all evolutionary biology. The problem has a clear catch-22 aspect: high translation fidelity hardly can be achieved without a complex, highly evolved set of RNAs and proteins but an elaborate protein machinery could not evolve without an accurate translation system. The origin of the genetic code and whether it evolved on the basis of a stereochemical correspondence between amino acids and their cognate codons (or anticodons), through selectional optimization of the code vocabulary, as a “frozen accident” or via a combination of all these routes is another wide open problem despite extensive theoretical and experimental studies. Here we combine the results of comparative genomics of translation system components, data on interaction of amino acids with their cognate codons and anticodons, and data on catalytic activities of ribozymes to develop conceptual models for the origins of the translation system and the genetic code.

  30. J-Mac,

    I do…however whenever I offer my own responses, they are not welcomed…

    That’s because you don’t really say anything. “lol … let the speculation begin … quantum physics … Darwin religion” seems to be the gist of it

    Whenever I offer the response based on authorities in science, such as Koonin, Venter, Dawkins, they not welcomed either…

    They aren’t commenting on my piece. Their words were written before mine, not in response to it. And you know Koonin, Venter and Dawkins accept evolution, don’t you? Should I just paste the words of someone else in response? Argument by glove puppet, I call it. This is a discussion forum. So discuss, already.

    Why should we agree with your reading of Venter that Mycoplasma’s STOP assignment to Tryptophan indicates no common origin, and not with Dawkins, me and just about everyone else? It can’t be enough that ‘Venter says’, because I can find someone equally eminent to say otherwise. And I say otherwise. I’m not an authority, but I do have a bit of biochemistry.

    So, yes:

    It seems that the only authority for you is you… In other words, further arguments are pointelss, unless I agree with based on your speculation…I have no reason to even read your further comments because you attempt to support an ideology with your biased point of view and not a shred of scientific evidence…You are not interested in anything but what you chose to believe…

    I have argued a case, in my own words, as clearly and concisely as I can muster. It’s based upon the facts of the case and biological process, making what I believe to be reasonable inferences, not what I ‘choose’ to believe about it. It’s quite detailed if that was all it boiled down to!

    You haven’t responded to it directly, other than to say how much you dislike it and how ‘speculative’ it is (how could it be otherwise? We are trying to reconstruct history from surviving clues). Then endless dumps of text from someone else that you think may be germane to the issue and fatal to my thesis, if only we search hard enough for the meaning you intend us to derive therefrom.

    You are right, I am the ultimate authority for my views. I can give reasons for them. But I could easily be wrong. If someone like, say, Larry Moran picks me up on a point of biochemistry, I’ll surely listen, because he’s a prof and I a mere graduate. Likewise Joe Felsenstein on the mathematical theory, or Dawkins – yet I have areas of disagreement with all these people.

    That, I think, is how it should be in science. Aren’t we supposed to be skeptics? It’s not about slavish parroting of authority. How would it ever advance if it was?

    Honestly, you Creationists make me chuckle. On the one hand, you suppose a clandestine Darwinist Mafia, and anyone who disagrees has the thumbscrews applied. But if one voices an independent opinion, it’s “look! Darwinists can’t even agree among themselves! Make your sodding minds up!”.

    Rant over. 😀

  31. Alan Fox:
    I see Joshua Swamidass has complimented Allan on his article. It must be worth featuring for the moment if it’s attracting interest off-site.

    ETA link

    Wow, that’s cool! Always nice to get a bit of positive feedback! 😀

  32. Allan Miller: Honestly

    I’m not particularly interested in any further analysis of someone’s rant when he gets to the “honestly” part…Can you infer why? Or would you like me to spell it out for you?

    BTW: I hope this OP continues to be featured…I ‘ve heard that many people on both sides of the controversy pay attention to TSZ and this OP…

    Allan Miller is becoming a superstar…🤣

  33. Mung: So not really science then. 😉

    What? Are you implying that the doing of the required science only applies ID and not evolutionary theory? Do you mean that Allan Miller can go on with his speculative fiction and never be questioned?

  34. J-Mac: Allan Miller is becoming a superstar

    No need to get jealous. I see in the comment thread that they also still remember you.

  35. Corneel: No need to get jealous. I see in the comment thread that they also still remember you.

    I feel flattered… but I have reserved all the glory for Dr. Swamidass after he published his book… I kind of wanted to get banned at PS… so that I wouldn’t divulge any of my strategies…
    Allan Miller already made me say more than I should have…
    I prefer to be viewed the way Allan does… It has the David vs Goliath effect…
    You know what I mean?

    Unfortunately there is a flip side to this.. Controversy tends to sell books…

    That’s why I wanted to get an advanced copy of Behe’s new book…I’m willing to pay whatever it takes …but legally…

    ETA: I forgot to quote Swamidass’ challenge:

    “Confessing Scientist

    Well I just read his book (Behe’s) with @nlents. Wait for the circus when it gets published and there will plenty of opportunities to clarify his current view with quotes”

    I think it’s pretty clear what Swamidass means… 😎

    https://discourse.peacefulscience.org/t/the-flagellum-is-not-a-motor/3801/218

  36. Corneel: No need to get jealous

    What’s that?
    Swamidass is trying hard to become a successful scientist and we all are trying to help him…I have nothing to envy.. maybe he is going to get a Nobel Prize for “maybe God guided the evolution of evolution”…why would care?
    For what I care most of Nobel Prizes should be returned and given to blind dumb luck….it’s bs…

  37. J-Mac: I do…however whenever I offer my own responses, they are not welcomed… Whenever I offer the response based on authorities in science, such as Koonin, Venter, Dawkins, they not welcomed either…

    So you agree with Eugene Koonin when he says?:
    Suzan Mazur: Are you saying this is the top discovery in evolutionary biology in the last 50 years?

    Eugene Koonin: The word “discovery” may not apply quite directly here. It’s a transformation of the whole science, which is based on a variety of discoveries. The very approach to evolutionary studies has changed completely. Not only the fact of evolution itself but the existence of deep evolutionary connections between different domains of life — to be concrete — evolutionary connections between, let us say, mammals, such as humans, and prokaryotes, bacteria and archaea, have become indisputable.These findings make questioning not only the reality of evolution but the evolutionary unity of all life on earth completely ridiculous and outside of the field of rational discourse.

    Right?

  38. J-Mac: I’m not particularly interested in any further analysis of someone’s rant when he gets to the “honestly” part…Can you infer why? Or would you like me to spell it out for you?

    No, spell it out. I don’t know why you have to be so coy all the time with all this perpetiual allusion. Are you calling me a liar? You Creationists really do make me chuckle. I should know; I’m the one doing the chuckling.

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