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
- Substitution of a STOP by an acid
- Acid-for-acid substitution.
- 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.
Dunno what you mean. Has inference no place in science?
It’s like phoodoo and his “secret” reasons why the world has to be full of pain and misery in order to achieve his gods goals of giving us the ability to grow. Those that live short brutish lives that we may extend our souls do it gladly, I’m quite sure….
Question away. That’s rather the point of writing the piece, for scrutiny, comment and criticism. That’s how science is done, not by inscription on tablets of stone.
You seem unable to formulate any actual critique; just a lot of ‘nothing-to-see-here’ meta.
But if you want me to be bound by a particular standard, hold yourself to it or be dubbed a hypocrite. If you think speculations are unjustified where they haven’t been subjected to direct experiment, then where does that leave ID?
Where I come from when you say “honestly” it is interpreted as if you had been bs-ing before…In your case however, your statement was right on the money… 😂
guano’ed a couple of posts.
wrong thread, kiddo
Except the inferences drawn by IDists? You appear to think they should be treated differently.
Inferences drawn by anybody are fine, but, to be scientific they need a scientific basis. Magical Being In The Sky that we’d rather not identify is not a very scientific inference. It gets worse if the posited Magical Being In The Sky that we’d rather not identify is based on nothing but semantic play / equivocations based on analogies and metaphors taken too far, misunderstood scientific concepts and findings, misapplied math, poor philosophy, double standards, and cherry-picking, toped with a huge load of resistance to correction.
I also approach inferences made by scientists with a lot of caution. Always looking for potential problems, for mistakes between concepts and referents, for misunderstood and poorly understood scientific findings and concepts, etc. The true difference is that scientists try and avoid them, while IDists just expect that nobody will notice. At least not their clientele.
Who needs further evidence that Entropy and his Darwinism/Materialism first ideology are all about evidence…wherever it may lead…
Can some please give me one reason why further discussions would not a waste of time?
The evidence for that is the evidence available that supports evolutionary theory in general and the structure and function of DNA in particular.
I think you’ve supplied ample evidence for that already. 🙂
Really???
We don’t even know exactly how enzymes work…You seem very confident that DNA is all there is in the evolutionary theory…
Moi?
How about this line of your:
” So what that there is not evidence for biogenesis?!! So what?!!
Do you need a link? Or, you are going to be able to find your favorite, scientific comment? 😉
Says the guy/gal whose ideology is “Magical-Being-In-The-Sky-no-matter-whether-there’s-any-evidence-for-or-against.”
As Alan said, you have provided ample evidence that any discussions with you would be a waste of time. I’m only answering for fun.
Sorry, but that you don’t know doesn’t mean that we don’t know. We have lots of progress in understanding ways in which enzymes work, from “binding to the transition-state” to nucleophilic attacks, sometimes with the added bonus of quantum mechanics calculations and simulations for some of the mechanisms. Oh. No. The enzymes don’t perform those calculations, scientists do.
I doubt that’s all that Alan thinks is involved in evolutionary theory. It looks more like what Alan wrote, besides the DNA acronym, didn’t register in your mind.
I agree, Entropy:
struck me as a particularly bad example of our supposed ignorance.
Of J-Mac’s ignorance, perhaps not.
Where I come from, that’s not what commencing a sentence with ‘honestly’ conveys. It’s more like ‘to be frank’. or ‘I must say’, or how the French might use ‘Vraiment’ to commence. Hard to see why you should think it an admission that my entire thesis on genetic codes was bs, simply because, at some later juncture, I used the term ‘honestly’ in relation to something else entirely, namely the inconsistency of many Creationists with regard to dissent and consensus.
Not me. I’m asking IDists to apply their own standards to their own field. They shove all this ‘lol speculation’ crap around, blissfully unaware that they are chucking their own theories under the bus. At no point have I ever given a ‘lol speculation’ response to an IDist. I just think evolution explains the data better. Saying ‘design’ does not explain the pattern in the variant codes; it is not an inference from the data, but a catch-all that can be invoked to explain everything and therefore nothing. The Electric Monk’s pale pink, as I say.
Chortle. Just picked up J-mac’s suggestion that I have been ‘kicked around’. Can’t say I noticed. UK politician Denis Healey once remarked over criticism from Geoffrey Howe: “it’s like being savaged by a dead sheep”…
J-mac’s only substantive comment so far has been to pick me up on the count of known variant codes, since I didn’t say when ‘last I looked’ was. The rest, endless Venter this, Venter that and ‘lol speculation’. A legend in his own lunchtime.
If one day you see the interior of a lab and at least attempt to test one of your unfounded speculations… unlike C. Venter, who has seen the first hand the evidence that your bluff doesn’t work…
Until then, your speculative evolutionary science will remain in the relm of wishful thinking…
It just hit me! Your bluff is even worse than I thought!
You are software engineer!
Well, until someone substantiates your science fiction novel about how genetic codes evolved, you can only keep on dreaming…😂
So what happens if II provide evidence? Make it worthwhile…
You both have faith, right? 😎
You have no clue what DNA_Jock is talking about now, do you? Unable or unwilling to read my comment for comprehension you left it to your imagination and prejudices, as usual. Right?
Your attitude makes it very very hard to feel compassion for you. I think I’m leaving you alone regardless. Not fair making fun of you when you have no clue whatsoever.
Venter! Venter! Get a room, already. He has never ‘experimented’ on genetic code evolution, to my knowledge. Do you have a citation? Or is an awkward grin in a round-table the very best you can muster?
And former biochemist. Venter is a current biochemist. Neither of us has any particular qualification in evolutionary science, but it’s not really about what one has on one’s cv. Do you accept Venter’s authority on everything?
Meantime, your qualification to speak on these matters is … ?
What do you think though, J-mac? How did Mycoplasma and our mitochondria come to have an assignment where our nuclei have a STOP? Why are variant codons almost invariably a STOP in one species or another?
It must have some significance. If not a clue to a possible pathway of genetic code evolution, then what?
Would it be a reasonable inference to suggest STOP codons are a late addition to the code?
I read internet blog posts. 🙂
How would that work, in theory. If things worked just fine without a stop codon why evolve them?
Competition where organisms wasting less resources in transcription/translation would out compete organisms that don’t have stops? Selection against potential secondary structures that might cover the coding part of the mRNA thus making it inaccessible? As coding regions evolved in ways that made them longer the translation mechanisms evolved to be less likely to fall off the mRNA by themselves, thus stops became advantageous?
Needs a lot of thinking and then putting them in ways that could be tested, but we’d expect that things weren’t that complicated at some time in the far past.
I don’t think so. How did proteins terminate before? STOP is the default. You don’t need to evolve anything special to achieve it; it just means there’s no tRNA for that codon. Which is likely to have been the common position initially.
Yeah, that’s fine; I’m not the one credential-mongering. This is what J-mac fails to grasp, when he does it: ID’s leading lights, and its most vocal advocates, are very light on scientific qualification, especially when it comes to evolutionary biology. Every time he opens his gob, he undermines ID.
I don’t know how things could possibly work without STOP.
It’s important to be aware of the energetic and spatial relations of peptide formation. Part of the energy for peptide bond formation actually comes from the base pairing of the codon and anticodon. You don’t get enough energy from mismatches, or gaps; you need the cognate anticodon. Further, the new tRNA docks immediately next to the most recent amino acid – any gap, and it’s too far away to bond. If there isn’t a tRNA, there’s nothing to dock to – no energy, and no proximity.
An early ‘no-STOP’ code would have to have a tRNA for every one of 64 codons, to provide the energy to form a peptide bond every time. I don’t see how that can be a sensible starting position. In my view, the tRNAs arose from fewer by duplication – ie, filling in STOPs, reducing their number, not increasing them. Ditto the aaRSs.
Maybe the THINGS would eventually evolve, perhaps? I mean at one point or another there must have been a life system that didn’t know how to stop, right?
I have a very distinct feeling that I have heard this argument before… I sure hope it was it from one of you as the support for your beliefs… Wouldn’t that be terrible if both of you made the same mistake?
You are a software engineer and former biochemist, right? Do you know math? Can you learn simple math? If you can, I’d like to help you…
Look up Grover’s algorithm regarding DNA and learn as much as you can. If you have an open mind, you will know what I have been talking about…
J-Mac,
A. Patel has been quiet on this subject since 2001, I think. Perhaps you could explain what you are getting at. All I have seen from you so far are extremely vague allusions.
Or is this another case of the “Special Relativity showing that there is no such thing on subatomic level as time” syndrome? All hat and no cattle?
Ingore him!
Do you know 100% how enzymes work?
Yes or No?
This is your only shot…
Another content-free contribution. If I read something by someone I might find something in it. “Take this, brother, may it serve you well”.
Meantime, on variant genetic codes …
If you ever have compared your posts with mine, and your clear demand to put other scientists’ findings in my own words, you would know what I’m dealing with…
I’m sorry that you can’t sleep… Good night!
Selection, Selection Selection. As if that’s the only possible option.
You and I agree. I don’t know why Alan would think that things could possibly work without a STOP.
For evolving something more complicated and seemingly “useful”? Sure. What else?
I like Allan’s scenario better though. It’s more compelling. It’s much more “economical” (less elements to consider, more Occam’s-Razor-ish, etc.)
Still, needs work and ways to try and test, to find evidence for or against. Etc. Could be called “the STOPs early/late problem.”
😀
I just realized that you’re confused Jock…
Grover’s Algorithm applies to the evolution of the genetic code… The QM math indicates it’s optimal…So, if it evolved it must have evolved from a simpler code, right? With trillions of microorganisms predicted how many of them could be predicted to use a simpler genetic codes?
” Replication of DNA and synthesis of proteins are studied from the view-point of quantum
database search. Identification of a base-pairing with a quantum query gives a natural (and first
ever!) explanation of why living organisms have 4 nucleotide bases and 20 amino acids. It is amazing
that these numbers arise as solutions to an optimisation problem. Components of the DNA struc-
ture which implement Grover’s algorithm are identified, and a physical scenario is presented for the
execution of the quantum algorithm. It is proposed that enzymes play a crucial role in maintaining
quantum coherence of the process. Experimental tests that can verify this scenario are pointed out.”
Enzymes are essential in the process of evolution, so that’s why I asked if you really knew how enzymes work…
D. AXE is one of the experimental scientists who questions our understanding of how enzymes really work… so does Venter… Synthetic enzymes are not even close to the “naturally occurring”ones… You should know something about that…
Thanks, J-Mac, for pasting the abstract of A.Patel’s last offering on this subject, from 2001. That was what I was referring to. He appears to have given up on the subject since. My guess is that the “experimental tests” that he “pointed out” did not pan out. Heh.
Thank you too for your clearest demonstration yet that you have utterly no clue what you are talking about. All that you appear capable of is cut-&-paste from articles that you think support your position, and vague allusions to QM. Woop-do-doop.
Clearly, you are unable to explain what you are getting at.
P.S. I designed and built a synthetic enzyme that was better than the naturally occurring one, so I do know something about that: I know that you are wrong.
I expected this from you… lol
What do you mean by better?
If Alan drives BMW M8 and I drive a Tesla…which one is better? They are both supper fast…but…
So in what sense are your enzymes better? Be specific
Patel realized the genetic code is optimal… he proved it… Should he be looking for the super optimal code? He hasn’t found the simpler code though… 🤣
Whatta bummer! Such a good idea… the evolution of the genetic code… But keep your fingers crossed! Evolutionary theory at least should predict a simpler code or you know…creationists will get their ideas that it was designed…😂
Again, you are confused…special relativity vs Einstein’s statement about time…
Could both be right? Could both be wrong?
Special relativity has been successful but so was Newtonian physics before Einstein…
I compare my posts with yours. Mine contain substantive arguments, expressed with crystal – I might even say breathtaking 😉 – clarity; yours obsequious grovelling towards someone you only imagine has a view congenial with your own; one that you seem unable to actually articulate. Lol.
Yup. It’s not just protein termination, or the chopping of existing proteins into fragments, but what STOP ‘means’ – it’s the absence of a tRNA: a null. It is much more probable that the tRNAs are all copies of a single ur-tRNA than that the code started with 64 different tRNAs and then evolved gaps.
The complication is that STOP is not just that. There are release factors invoked when a STOP is encountered, which break the bond between the last tRNA and its amino acid. Because that amino acid is attached to the rest of the peptide, this effectively releases the peptide. So I might agree with a STOP-early release-factor-late scenario. That is, primitive STOP may be achieved by tRNA absence alone, with some other, perhaps now absent, means of breaking the ester bond with the last tRNA (this is an easy reaction to catalyse). More recently, active release factors took over.
RFs recognise codons. In prokaryotes, RF1 deals with UAA and UAG (3rd position = either purine), while RF2 recognises UAA and UGA – (2nd position = either purine). In eukaryotes, erf1 recognises all 3 (2 and 3 can both be either purine – one puzzle is how the eukaryote system avoids UGG).
So, to fill in a STOP – even after RFs have evolved – you just need a tRNA, and an aaRS promiscuous enough to charge it already in place. The tRNA will compete with the RF for the codon. Going the other way is harder. You need to extend the specificity of an RF, and get rid of a tRNA – two changes.
So, for many reasons, I don’t think assignment -> STOP is the likely direction of travel.