Wednesday, February 22, 2017

Sloppiness in translation initiation

There are two competing worldviews in the fields of biochemistry and molecular biology. The distinction was captured a few years ago by Laurence Hurst commenting on pervasive transcription when he said, "So there are two models; one, the world is messy and we're forever making transcripts we don't want. Or two, the genome is like the most exquisitely designed Swiss watch and we don't understand its working. We don't know the answer—which is what makes genomics so interesting." (Hopkins, 2009).

I refer to these two world views as the Swiss watch analogy and the Rube Goldberg analogy.

The distinction is important because, depending on your worldview, you will interpret things very differently. We see it in the debate over junk DNA where those in the Swiss watch category have trouble accepting that we could have a genome full of junk. Those in the Rube Goldberg category (I am one) tend to dismiss a lot of data as just noise or sloppiness.

Before I get howls of protest about false dichotomies, let me make it clear that there's quite a bit of middle ground. Some biological systems are, indeed, highly accurate and finely tuned by natural selection. But most are not. They are the product of evolution as a tinkerer resulting in a system that's just good enough for survival. What some see as essential complexity, others see as Rube Goldberg machines. They work, but that's not the way you would have designed it if you had the power.

Let's see how this distinction plays out in a recent paper that's just been posted on the Nucleic Acids Research website.
Hecht, A., Glasgow, J., Jaschke, P.R., Bawazer, L., Munson, M.S., Cochran, J., Endy, D., and Salit, M. (2017) Measurements of translation initiation from all 64 codons in E. coli. Nucleic acids research. [doi: 10.1093/nar/gkx070] [bioRixv]
First, a bit of background. Translation in bacteria begins near the 5′ end of the mRNA at a specific initiation codon that's usually AUG. AUG is usually a methionine codon but in the context of initiation it specifies a particular tRNA called fMet-tRNAi because it specifies a modified methionine called N-formylmethionine.1 This initiator tRNA is only used during translation initiation because it binds to a specific initiation factor, IF-2. (All of the other aminoacylated tRNAs in the cells are bound in a complex with elongation factor Tu (EF-Tu).)

Initiation is special because the initial amino acid (fMet) must be bound to the ribosome complex in the absence of a growing polypeptide chain. It has to be inserted into the P-site that normally contains a tRNA bound to a polypetide chain. During elongation the incoming aminoacyl-tRNA is bound to the adjacent A-site (aminoacyl site).

How does the translation complex assemble at the initiation codon and not just at any methionine codon? As you might imagine, the selection of the correct codon for initiation depends on the sequence of bases in the immediate vicinity. In bacteria, the selection depends on a short sequence upstream of the proper initiation codon. It's called the Shine-Dalgarno sequence and it forms base pairs with an exposed bit of the 16S RNA in the small ribosomal subunit. This is how the translation complex is directed to assemble at the point where translation will begin.


Hetch et al. looked at the initiation codons in bacterial proteins and found that 82% of them were the cannonical AUG that's in most of the textbooks. Almost 14% were GUG (valine) codons that the initiator tRNA sees as a start site because it's adjacent to a Shine-Delgarno sequence. FMet is inserted at this site because two of the three bases match the standard initiation codon. About 4% of initiations occur at UUG (leucine)—another two out of three match. None of this is news. It's been known since the 1970s that some initiation codons are GUG and UUG (Miller, 1974).

The bottom line is that 99.95% of all initiation events occur at AUG and the two related sequences GUG and UUG. It means there's a little bit of sloppiness in forming the correct initiation complex.

Hetch et al. noted there were four other codons that popped up in the database, albeit at extremely low frequencies. The others are CUG, AUU, AUC, and AUA. All of them match two of the three bases in the standard initiation codon. No surprises there.

The authors wondered if other codons could be mistakenly used if they were in the right position relative to the Shine-Delgarno sequence so they constructed a series of plasmids to test them. Here's what some of those plasmids look like ...


The green part is the reporter gene whose protein product can be detected easily. (GFP stands for green fluorescent protein.) Transcription begins at a bacteriophage T7 promoter and ends at a T7 terminator. This ensures that a lot of transcripts will be made when the plasmid is inserted into E. coli cells.

RBS is the ribosome binding site otherwise known as the Shine-Delgarno sequence. In this case they used a very strong RBS, AGGAGA, to make sure that the translation complex was bound to the mRNA beside the initiation codon. Hetch et al, then tested every codon for its ability to initiate protein synthesis at a site that began eight bases downstream of the RBS. Here's the result ...


As expected, the best codons are AUG and its two relatives, GUG and UUG. Other codons are much less efficient with frequencies that are 0.01-0.1% of the AUG standard. There were 17 codons that didn't work at all.

This is all consistent with a Rube Goldberg worldview where sloppiness is the norm. In this case, translation initiation is pretty good but mistakes can be made. The elongation process of translation is also error-prone with a typical misincorporation rate of about 10-4 or one error in every 10,000 reactions. Most of those errors are due to single mismatches in the triplet codon.

The authors are aware of this view because they say,
Almost all E. coli genes with non-AUG start codons initiate with methionine as the N-terminal amino acid and such events are not considered to be errors in translation initiation. By this same logic, we argue that translation initiation of genes with other non-AUG codons, in which methionine is observed as the N-terminal amino acid, should not be considered an error. However, those wishing a strict interpretation of the central dogma could consider such events to be errors in translation initiation. All biological processes are governed by processes that imply a certain rate of unlikely events, and such unlikely events are often referred to as errors, failures, or leaks.
This is not quite correct. As with the case in DNA binding proteins, optimal efficiently is achieved with a perfect match to the consensus sequence—in this case AUG—but close matches can be selected when less-than-perfect expression is beneficial. Thus, there are many weak DNA binding sites that are selected in bacteria because they reduce expression below optimal levels. The weak lac promoter is a classic example.

There may well be genes where GUG and UUG are used for a reason. That doesn't change the conclusion that there's an optimal initiation codon. This explanation for the low frequency of GUG and UUG initiation codons in some genes has been around for decades. It is almost certainly correct.

Hecht et al. make this point but I think they get carried away with Swiss watch thinking.
However, focusing only on the statistical likely outcome risks overlooking any advantageous aspects of rare but purposeful possibilities. Viewing non-cannonical start codons without commitment to traditional dogma may reveal them as a potential feature, rather than an error, in gene expression. [Translation, we have an open mind, not bound by traditional dogma.]

For example, there may be evolutionary utility to translation initiation from non-canonical start codons. Research with yeast has shown gradual transitions of genetic sequences between genes and non-generic ORFs in related species. We can imagine a scenario wherein, over evolutionary time scales, point mutations could create a weak non-canonical initiation codon downstream of an RBS. The small amounts of protein produced from such an ORF, if beneficial to an organism, could select for further mutations that increased translation efficiency up to a point where the gene product more directly impacted organismal fitness. Further mutations could then be selected that tune for optimal expression dynamics in a given genetic context.
This is confusing but the basic idea is sound. Non-canonical codons can be selected. However the authors go a bit too far in suggesting that ALL non-canonical initiation codons could be significant and could cause us to re-evaluate our understanding of translation.
The presence of frequent but very low-level expression of proteins via non-canonical start codons would have widespread implications for genome annotation, cellular engineering and our fundamental understanding of translation initiation. We encourage reconsidering definitions and further exploration of what is considered a start codon.
By promoting the novelty of their work, and down playing what was already known, the authors attracted the attention of science journalists who read the press release but didn't know the literature. Here's how the paper was reported on phys.org: Start codons in DNA may be more numerous than previously thought.
For decades, scientists working with genetic material have labored with a few basic rules in mind. To start, DNA is transcribed into messenger RNA (mRNA), and mRNA is translated into proteins, which are essential for almost all biological functions. The central principle regarding that translation has long held that only a small number of three-letter sequences in mRNA, known as start codons, could trigger the production of proteins. But researchers might need to revisit and possibly rewrite this rule, after recent measurements from a team including scientists from the National Institute of Standards and Technology (NIST).

...

The implications of the work could be quite profound for our understanding of biology.

"We want to know everything going on inside cells so that we can fully understand life at a molecular scale and have a better chance of partnering with biology to flourish together," said Stanford professor and JIMB colleague and advisor, Drew Endy. "We thought we knew the rules, but it turns out there's a whole other level we need to learn about. The grammar of DNA might be even more sophisticated than we imagined."
Yes, it's true the grammar might be more sophisticated than we imagined; however, it could also be more sloppy than we imagined.


1. the 21st amino acid.

Miller, J.H. (1974) GUG and UUG are initiation codons in vivo. Cell, 1:73-76.

70 comments :

  1. I think it would be interesting to do some comparative genomics to support or rule out what the authors are suggesting. If they compare a gene in E Coli that uses GUG or UUG for Start to a variety of other species would they see most others using AUG? It might suggest that AUG to GUG mutations are tolerated in some proteins.
    Although I take the Rube-Goldberg view mainly, I have to say that I dont see much support for it in this particular work. Even a Swiss watch can function after a few perturbations. It seems to me that its the particular architecture of a system, where incremental changes to a preexisting but different system is the only explantation for its structure, that supports the RG view.

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    1. I don't think there's any doubt about the fact that GUG and UUG can serve as initiation codons in some cases. I suspect that AUG is the preferred initiation codon in highly expressed genes but in other genes the less efficient codons can be tolerated. They may even be selected to reduce the frequency of translation.

      However, I doubt very much that the other codons could be beneficial because their efficiency is so low.

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    2. So do you think it could be the case that if you looked at a wide variety of genes across diverse species, AUG would always be the consensus start codon but individual lineages may have switched to GUG or UUG, and in those cases where there was a switch it would tend to be in proteins expressed in low amounts or subject to negative feedback regulation?

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  2. The error rate of T7 polymerase is ~1/10000, so isn't it also likely that some proportion of this is transcription error rather than translation error?
    https://www.ncbi.nlm.nih.gov/m/pubmed/10995224/

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    1. I actually suggested that to the authors (they are colleagues of mine), though I thought the numbers would be too small. However, I was assuming that the RNAP error rate was about 10 times lower than the reference you cite. It's worth looking into.

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    2. The authors address this issue in their paper. They don't think it's a serious issue and I agree with them.

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  3. Translation initiation might be less sloppy then it seems. Did you consider the results of Chuan He?

    http://www.nature.com/news/an-epigenetics-gold-rush-new-controls-for-gene-expression-1.21513#reading

    The function of methylation of Adenine on RNAm might be to enhance or in any case regulate transcription. Isn't it possible that the methylated adenine's within single codons enhance initiation of transcription?

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    1. Methylation of adenines in mRNA is not important in bacteria.

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    2. Thanks for the great news Marleen.

      Last year I talked about the planning stages for Son of ENCODE called the E4 (Enabling Exploration of the Eukaryotic Epitranscriptome) project.

      From the link:
      "The mark that pushed He to the forefront of EPITRANSCRIPTOMICS was first discovered on mRNA in 1974 (ref. 4)."

      There could be some awesome scientific discoveries coming down the pike. And the Rube Goldberg machines will be even more amazing.

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    3. Sal doesn't mention it here, but he interprets "Rube Goldberg machines" as evidence of design precisely because they are needlessly complex and bizarre. That's God telling us how clever and creative he is and therefore that he exists. He can't lose: when a feature of an organism is simple and elegant, that's evidence for God; when it's complicated and kludgy, that's evidence too.

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    4. Which is yet another example of how creationists, no matter how well-informed they are, fundamentally misunderstand the scientific method. The idea is not to construct hypotheses that can accommodate as many potential observations as possible. The goal, rather, is to construct hypotheses that are confirmed by the observations that are actually made, and which would be falsified by observations that, it turns out, are not made. A hypothesis that remains standing because it can accommodate any observation that is even conceivable is not a strong hypothesis, but is rather a very weak one. The "design" hypothesis is an example of this.

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    5. The Nature article hypes the presence of methyl-adenosine in mRNA. The discovery of m6A in mRNA is 40 years old and since its discovery the role of m6A modifications have been well-studied in several mRNAs.

      The latest news is that there may many more such modifications that anyone previously suspected but near the end of the article there's an interesting paragraph.

      However, the significance of m6A isn't yet clear, [Yang] Shi says. He points out that even with the latest technology, the modification is only borderline detectable and its precise location cannot be mapped. And the pattern of m6A will probably vary from tissue to tissue.

      There's another paragraph in this review that makes me deeply skeptical of its overall quality and accuracy.

      The governing rule of molecular biology—the central dogma—hold that information flows from DNA to RNA to protein. Many scientists therefore viewed mRNA as little more than a carrier, carrying the genetic information encoded in a cell's nucleus to the protein factories in the cytoplasm. That's one reason why few researchers paid much attention to the modifications made to mRNA.

      This is more than nonsense, it's patently false. Researchers have paid lots of attention to mRNA modifications. There have been tons of papers on processing and modification such as splicing, caps, and polyadenylation, in addition to studies on internal nucleotide modifications.

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  4. Machines constructed at the nano-molecular level will always be subject to thermal and quantum noise. All that Brownian motion is like a tornado down there, so as a matter of principle things won't work like a Swiss watch but a Rube Goldberg machine that constantly repairs itself from spurious defects. A consequence of Claude Shannon's (father of information theory) theorem is that if one wants to store lots of information compactly, one allows lots of spurious errors to happen and then remediate them later. So if one constructs nano-molecular machines that are fragile enough to be blown apart by all the noise at the molecular level, they will be Rube Goldberg like as a matter of principle.

    One could then say, "well why don't you make the molecules non-fragile and always at equilibrium." No problem, we call that the dead state.

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    1. I understand where you're coming from. Everything is designed and nothing will shake your belief in an intelligent designer even if he/she/it doesn't look very intelligent.

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    2. I'm always curious to hear what creationists think living things would look like if they had arisen thru evolution, and how this would differ from the "design" they think is shown by living things as they are.

      If they have no answer, it would seem their position is that life, in whatever form, could only arise thru design. If so, I don't know why they don't just stick to that argument, rather than getting involved in the messy and (for them) confusing specificities of biology.

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    3. A consequence of Claude Shannon's (father of information theory) theorem is that if one wants to store lots of information compactly, one allows lots of spurious errors to happen and then remediate them later.


      I see you understand information theory as well as you do evolutionary theory.

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    4. I understand where you're coming from. Everything is designed and nothing will shake your belief in an intelligent designer even if he/she/it doesn't look very intelligent.

      Well Larry, same applies to you don't you think?

      Nothing will shake your belief in random processes behind the origins of life even if the best you have from YOUR current prospective is the Designer appears to be not as intelligent as your set of beliefs would allow. As far as I can see, the only arguments you can have are:

      1. The Intelligent Designer got sloppy (from your point of view of course). As an intelligent being who recognized the supposed flaw, you can prove your point by re-designing things you are not satisfied with from scratch and not just the ones Someone had already designed. How difficult could this be for an intelligent being like yourself to do better than the random processes had done it before? It should be a piece of cake for a clever guy like you.
      2. The Intelligent Designer designed it all good but not perfect and for one reason or another allowed his design to run its course and entropy took over its natural course deterioration overtime.

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    5. "The Intelligent Designer designed it all good but not perfect and for one reason or another allowed his design to run its course and entropy took over its natural course deterioration overtime."

      I expect that Larry would hold to the idea that death is an evolved feature....an evolutionary accomplishment.

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    6. @Jass

      If you have any evidence for the existence of something that could have designed life then this is the perfect forum to present it.

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    7. It's so cute watching creationists try to think: No designer of which we know could create life. Therefore, life could only have been created by a designer. I wonder by what kind of logic does that argument work.

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    8. If you have any evidence for the existence of something that could have designed life then this is the perfect forum to present it.

      I have to admit Larry I'm a bit disappointed with your lack of real response, though I do respect your views, as I should, since we live in a "free society" for now.

      Well, the evidence for the designer of life I have would not satisfy you Larry, I'm pretty sure of that.

      But the evidence that you must have that life wasn't designed because it originated by random processes would create no need for me to present my evidence at all, would it? So the main reason why we have these pointless discussions here is because you must be withholding the key evidence that would have settled this issue long time ago but you must be playing everyone with it.

      Since myself and many others here would no doubt expect scientific evidence for your views of life's origins and design (it's funny how it is so hard to avoid the word "design" even for materialists), why don't you do it and get it over with?
      The way I wrote this comment is in a way that you have the ammunition to present your beliefs to the public accordingly. I have a feeling that it would be a major blow of disappointment if you dodged this issue too...

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    9. I expect that Larry would hold to the idea that death is an evolved feature....an evolutionary accomplishment.

      Death had to have been evolved somewhere, somehow if you are a materialists but not too early! The materialistic idea has to survive somehow through the alleged process called endosymbiosis...and then it can die..naturally...

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    10. It's so cute watching creationists try to think: No designer of which we know could create life. Therefore, life could only have been created by a designer. I wonder by what kind of logic does that argument work.

      Why don't you prove us wrong? You must have the scientific evidence no one can deny. Right? What's wrong with you? Let us all see the evidence nobody can deny!

      This is your opportunity to convince the world that you are right! Just do it!

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    11. Jass,

      "Death had to have been evolved somewhere..."

      So it is thought, and I would suppose senescence as well. I wonder, what prefix would be attached to selection to account for the evolution of aging and death?

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    12. Jass:
      "Well, the evidence for the designer of life I have would not satisfy you Larry, I'm pretty sure of that."

      The evidence in favor of heliocentrism didn't satisfy the religious institutions when heliocentrism was postulated, but they had to admit it was right.
      Your evidence in favor of a designer might not satisfy the host, but you know, he might have to admit you're right.

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    13. "non-fragile and always at equilibrium", ... we call that the dead state, and God, we call that God too

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    14. I should know better by now, but it continues to astonish me how little creationists understand about evolution, despite their seeming to spend a good amount of their waking hours thinking of little else. Perhaps txpiper and his little friend Jass will regale us with their theories of how evolution would proceed if death didn't occur.

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    15. Jass said,

      But the evidence that you must have that life wasn't designed because it originated by random processes would create no need for me to present my evidence at all, would it? So the main reason why we have these pointless discussions here is because you must be withholding the key evidence that would have settled this issue long time ago but you must be playing everyone with it.

      I don't know how life began. I don't see any reason to rule out that it arose by entirely naturalistic means.

      I don't see any evidence that life on Earth was created by outside beings who were capable of such a task. And I don't see any evidence that such beings exist.

      YOU are the one who claims to have the answer. Let's see your evidence.

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    16. Larry
      "
      I don't see any evidence that life on Earth was created by outside beings who were capable of such a task. And I don't see any evidence that such beings exist.

      YOU are the one who claims to have the answer. Let's see your evidence."

      The evidence is we see is life, and it is enormously complex yet has a very repeatable process. It is driven by sequential information (DNA) which is virtually impossible to organize without intelligence.

      Your position that makes the requirement direct evidence denies inductive reasoning which is the basis of science.

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    17. The evidence is we see is life, and it is enormously complex yet has a very repeatable process. It is driven by sequential information (DNA) which is virtually impossible to organize without intelligence.

      You seem not to understand the distinction between evidence and an unsupported assertion. Learn the difference, then give it another try.

      Your position that makes the requirement direct evidence denies inductive reasoning which is the basis of science.

      ...says the guy who claims that common descent is an "untested hypothesis". You don't understand science or logic, Bill, but I'll give you this: You're a world class expert in hypocrisy.

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    18. Nah, Bill's strongest force is willful incompetence.

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    19. LS
      "You seem not to understand the distinction between evidence and an unsupported assertion. Learn the difference, then give it another try."

      Is bacteria, a self replicating organism, evidence of something or an assertion?

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    20. Nah, Bill's strongest force is willful incompetence.

      If there was any doubt, Bill just dispelled it.

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    21. "Is bacteria, a self replicating organism, evidence of something or an assertion?"

      Are you saying bacteria are intelligent? Remember, you argued that DNA can only be "organized" (whatver the hell that means) by intelligence. But now you're blathering about bacteria, as if they are somehow evidence that only "intelligence" can "organize" DNA. Which seems to suggest you think bacteria are intelligent.

      Well... I guess to you they might seem so.

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    22. “Perhaps txpiper and his little friend Jass will regale us with their theories of how evolution would proceed if death didn't occur.”

      Well first, I believe in adaptation, but not in evolution as you perceive it. So I don’t have any reason to theorize about it. That said, why would you think death is necessary? What was the selective advantage in acquiring programmed aging and death? Is natural selection keeping niches open? Planning ahead?

      ===

      “Are you saying bacteria are intelligent?”

      Interesting question. When replication enzymes detect, excise and repair errors, is there cognizance involved? Are they smart?

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    23. Well first, I believe in adaptation, but not in evolution as you perceive it. So I don’t have any reason to theorize about it. That said, why would you think death is necessary?

      Sorry if my question was too difficult for you to understand. I'll try dumb it down a bit.

      I know you deny evolution. However, you are aware that the theory of evolution exists, correct? And even though you reject it, I presume you believe you have some understanding of the theory. So with this supposed understanding in mind, explain to me how evolution would proceed if death didn't occur. For instance, how would natural selection operate if nothing ever died? Don't be shy, flex those brain muscles, and show us what you've got!

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    24. “how would natural selection operate if nothing ever died?”

      So, programmed death was selected so natural selection could take place. Very good.

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    25. Mikkel
      "Are you saying bacteria are intelligent? Remember, you argued that DNA can only be "organized" (whatver the hell that means) by intelligence. But now you're blathering about bacteria, as if they are somehow evidence that only "intelligence" can "organize" DNA. Which seems to suggest you think bacteria are intelligent."

      Bacteria is evidence. What is the first cause of bacteria. Is intelligence required to design bacteria or can bacteria emerge from a trial and error process? What is the minimum cell complexity where self replication can occur? Do we discount design intelligence just because we can't observe any other being capable of design other than human?

      If according to Aristotle there are 4 types of causes and everything in nature has a cause. Does logic bring us to an uncaused cause to avoid an infinite regress?

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    26. “how would natural selection operate if nothing ever died?”

      Think bacteria.

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    27. Is intelligence required to design bacteria or can bacteria emerge from a trial and error process?

      They can emerge from trial and error. We know this from the fact that we directly observe random, unguided processes produce novel biological functions and structures, in both natural and controlled laboratory settings.

      What is the minimum cell complexity where self replication can occur?

      A cell is not required for self-replication.

      Do we discount design intelligence just because we can't observe any other being capable of design other than human?

      That's part of the reason. But the main one is that there is no biological fact that cannot be better explained by evolution than by "design", given that evolution consists of a well defined and specific theory involving known processes abundantly supported by direct evidence as well as inductive reasoning. Whereas advocates of "design" do not even have the most rudimentary hypothesis regarding how this "design" process occurs. As you admit yourself, this is a matter that can only be answered thru theology and philosophy. Which is the same thing as saying it cannot be answered at all.

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    28. Bacteria is evidence. What is the first cause of bacteria.

      What could be the first cause of anything powerful and intelligent enough to design bacteria? The "problem" you pose is multiplied exponentially under any intelligent design hypothesis. Thus Aristotle says you're barking up the wrong tree of life.

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    29. If according to Aristotle there are 4 types of causes and everything in nature has a cause.

      He didn't know about quantum mechanics.

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    30. So, programmed death was selected so natural selection could take place. Very good.


      That's silly! We all know it's because an intelligent being created by a deity blowing on dirt ate an apple offered him by his rib made animate by this same deity, due to the rib being tempted by a lizard created by the same deity in order to set in motion the events that would toss His perfect creations out of the perfect home He'd made for them.

      So logical and simple!

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    31. What was the selective advantage in acquiring programmed aging and death?


      It didn't need to be "acquired," as here in the real world nothing is eternal.

      Animals die, is that because they're sinful? But how can they sin without souls? And why did God create little puppy dogs in such a way that they'd die, and that other animals would have to die in order for them to survive?

      Or is it simply because life arose imperfect and subject to all the regular physical laws in the first place, and living things survive as long as the good-enough-but-not-perfect processes that keep them alive can last, eh?

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    32. He didn't know about quantum mechanics.

      So far at least, quantum mechanics doesn't violate causality. It does necessarily make prior prediction of causation a matter of probability.

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    33. Think bacteria.

      Right. I should have specified sexually reproducing organisms. My bad.

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    34. So far at least, quantum mechanics doesn't violate causality.

      It does in the naïve sense that Aristotle used it, such that the existence of a "first cause" could be argued. Aristotle, of course, lived over 2000 years ago, so his ignorance is understandable. Theologians who continue to trot out that argument today have no such excuse.

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    35. "Or is it simply because life arose imperfect and subject to all the regular physical laws in the first place, and living things survive as long as the good-enough-but-not-perfect processes that keep them alive can last, eh?"

      No, death is the result of deliberate biological processes.

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    36. No, death is the result of deliberate biological processes.


      For God so loved the world that he decreed cute little polar bear cubs would starve to death unless cute little fur seal pups died horribly in the jaws of the cute little polar bear cubs' mothers.

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    37. Right. I should have specified sexually reproducing organisms. My bad.

      Think Saccharomyces cerevisiae (single-celled yeast) or Chlamydomoans (single-celled green algae).

      The idea that death is biologically programmed makes no sense when dealing with single cell species that divide mainly by fission. It's true that they can't continue to divide forever but death is usually due to starvation or being eaten and not by senescence.

      Since life was predominantly single-celled for several billion years, it seems unlikely that evolution selected for death.

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    38. The idea that death is biologically programmed makes no sense when dealing with single cell species that divide mainly by fission.

      It doesn't make much sense for multicellular organisms either, though it does for individual cells in clonal colonies. I don't know of anyone who claims that senescence is positively selected in any species. Bet the creationists here don't either. And yet txpiper is able to claim that "death is the result of deliberate biological processes", though he has no idea what those processes might be.

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    39. “Since life was predominantly single-celled for several billion years, it seems unlikely that evolution selected for death.”

      From Nick Lane’s book “LIFE ASCENDING: THE TEN GREAT INVENTIONS OF EVOLUTION”,
      Chapter 10 - Death

      http://nick-lane.net/chapters/life-ascending-chapter-10-death/

      The following is not included in the above excerpt. It was taken from a Google book review:

      “From space they look much the same as modern algal blooms; and under the microscope, the ancient fossils are virtually identical to modern cyanobacteria, like Trichodesmium. The blooms persist for weeks, their rapid growth stimulated by minerals carried out to sea from rivers, or dredged up from the ocean depths by rising currents. Then overnight they vanish, dissolving in the water, which once more reflects only the lifeless red sky. Today, too, vast ocean blooms dissolve overnight without warning.

      It’s only recently that we’ve come to appreciate what’s going on. These vase hordes of bacteria don’t just die: they kill themselves quite deliberately. Each and every cyanobacterium contains within itself the machinery of death, an ancient system of enzymes remarkably similar to those in our own cells, dedicated to dismantling the cell from within. It’s so counterintuitive, the idea of bacteria liquidating themselves, that reseachers have tended to overlook the evidence; but it is now too strong to ignore. The fact is that bacteria die ‘deliberately’, and the genetic evidence, marshalled by Paul Falkowski and Kay Bidle at Rutgers University, New Jersey, implies that they’ve been doing so for three billion years. Why?”


      I don’t think Lane’s answer is particularly enlightening, but he does a pretty good job of explaining that death is an intentional trait. He continues:

      ”Or rather, they don’t simply die: they die complcatedly. Quite how the complex machinery of death first evolved is uncertain. The most plausible answer is through interactions with phages, a type of virus that infects bacteria. Viral particles are found in modern oceans in shocking abundance: hundreds of millions of them per millilitre of seawater, which is at least two orders of magnitude more than bacteria; and they almost certainly existed in comparable numbers in ancient times. The unceasing war between bacteria and phage is one of the most significant and unsung forces in evolution. Programmed death likely emerged as one of the earliest weapons in this war.”

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    40. "I don't know of anyone who claims that senescence is positively selected in any species. Bet the creationists here don't either. And yet txpiper is able to claim that "death is the result of deliberate biological processes", though he has no idea what those processes might be."

      Aging and death are post-original design modifications. Do a search for 'senescence genes'.

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    41. Aging and death are post-original design modifications. Do a search for 'senescence genes'.

      I find a lot about cellular senescence in clonal colonies (such as yourself). Try again. I don't think that's what you mean to be talking about. But I don't think you quite know what you mean to be talking about.

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    42. Since life was predominantly single-celled for several billion years, it seems unlikely that evolution selected for death.

      Is life not still predominantly single-celled?

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    43. @txpiper

      Nick Lane is correct in the sense that some species exhibit programmed cell death. He's wrong to imply that this is an ancient trait and he's wrong when he implies that all bacteria commit suicide deliberately. Death is not necessary for evolution and death has not been selected over life.

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    44. OK, obviously there are some basic concepts I thought I understood, but didn't. Thanks for the help, everyone!

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    45. @Larry

      “He's wrong to imply that this is an ancient trait and he's wrong when he implies that all bacteria commit suicide deliberately.”

      I think Nick is wrong about lots of things, but he does make a good case for his views. In particular, he notices that the mechanism for suicide, whether it is individual cells or a complex organism, are purposeful and complicated.

      The bigger question would be about the hows and whys of self-demise. To attribute it all to natural selection acting on a series of random DNA replication errors is absurd. This is one of those junctures where love for the results surpasses the limits of the evolutionary mechanism. The selection fairy is not smart enough to plan ahead.

      “To every thing there is a season, and a time to every purpose under the heaven: A time to be born, and a time to die…”

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    46. To attribute it all to natural selection acting on a series of random DNA replication errors is absurd.

      Gosh, but that's what your source (Nick) does, and why is that?

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  5. Cultural note. In the UK we say "Heath Robinson" not "Rube Goldberg". From Wikipedia:

    In the UK, the term "Heath Robinson" entered the language during the 1914–1918 First World War as a description of any unnecessarily complex and implausible contrivance, much as "Rube Goldberg machines" came to be used in the US from the 1920s onwards as a term for similar efforts. "Heath Robinson contraption" is perhaps more often used in relation to temporary fixes using ingenuity and whatever is to hand, often string and tape, or unlikely cannibalisations.

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  6. Reading about translation I just thought of another case of interest. Mitochondria are essential for eukaryotes. They carry their own genome to code for proteins and RNAs that either need to be translated within the mitochondrion or haven't had the chance to be transferred to the nuclear genome. Despite the importance of mitochondria and their genome, different tRNAs have been lost in different animal phyla, leaving orphan codons that cannot be translated and have been reassigned in different ways using the other tRNAs. That's clearly far from optimal and is in line to what Sidney Brenner elegantly stated (I read it in Spanish, here my poor translation): "If Maths are the art of perfection and physics the art of optimality, Biology is just the art of being satisfactory: anything is ok while it works"

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  7. I enjoy reading the comments on this blog. As a non-scientist, I can only conceive of the subject of genomics and all the details we find in there as an example of how natural evolution leads to an intricate and unneccesarily messy 'machine' that no designer worth his salt would ever have constructed. Mao didn't mind the color of cats as long as they would catch mice.

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  8. Over twenty years ago, I got a creationist sound casette: 'Subversives are spreading the mass delusion that we came from animals who arose out of goo. People believe it based on authority, not on the merits.' He warned the propaganda was seeping into primary schools

    I challenged my teachers in class, and their response fell into the archtypal trap: They failed to refer me to specifics, but said science had proved it. "Ah Ha! Argumentum ad Authoritarianism", although I didn't know the phrase when I was 8 years old. Over years, this feedback absolutely convinced me that I could topple the house of cards and resolved to study this doctrine and ultimately discredit evolution. Unlike this poor fellow liarsfordarwin, I had the self awareness to understand were I was going wrong.

    (1)Social trust mechanisms can extremely reliable, it can gather and vet far more information than we can on our own. Despite it's limitations we all stake our lives on it. The scientific method gives powerful tools to correct those limitations, but the creationists are taught scientists cannot be trusted. When the reading public fail to allow for the fact that creationists discount their priors, their unfamiliarity with scientific detail unintentionally reinforces the creationist. The creationists triumphally note base rate fallacy: that others fail to account for their misconceptions serves to buttress their ideology.

    (2)The better an area of science is understood, the more information is available, the lest investment is required to informally test it. A good analogy is object oriented programming: When an object or method performs adequately, we only need to unerstand the parameters and return values to make use of it. Creationists become trained to
    a) expect people's belief in evolution correspond to their level of expertise. They are reinforced by people believe in evolution who do not understand it well.
    b) they lack the level of INTEREST in evolution that would be required to understand it. They are reinforced by their own dissatisfaction at the answers of those who understand.

    Thus creationists publish books which credit their own skepticism for what their lack of curiosity has achieved.

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    Replies
    1. Thus creationists publish books which credit their own skepticism for what their lack of curiosity has achieved.

      Nice. Lack of curiosity, and/or fear of learning that which contradicts their world view.

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    2. “creationists publish books which credit their own skepticism for what their lack of curiosity has achieved”

      Creationists question how in hell random DNA replication errors resulted in strategically positioned check valves in veins, or assembled a ten-layer retina. Your curiosity was exhausted when you settled for sappy answers before you ever started asking serious questions.

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    3. Tx, amazingly you've missed these bullits:

      Creationists become trained to
      a) expect people's belief in evolution correspond to their level of expertise.


      Which is something you not only show time and time again in your remarks. But something you've also admitted, you've never studied evolution because you don't believe in it.

      They are reinforced by people believe in evolution who do not understand it well.

      Clowns like Bill, jass, otangelo et al.

      b) they lack the level of INTEREST in evolution that would be required to understand it.

      Again, you admitted to have no interest in learning about evolution.

      Which leads to really stupid questions like: "Creationists question how in hell random DNA replication errors".
      You're attacking something you don't understand, something you don't want to understand and something you will never learn to understand unless you try to learn what you're attacking, which you already admitted you never want to do.

      So what the hell are you doing here? Hoping to convert some lost souls to strengthen your claim of a slot in heaven?

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    4. Your curiosity was exhausted

      Simply and demonstrably incorrect. It still has not been (exhausted). Out of amateur interest I do a wide range of reading in academic papers and popular literature regarding evolutionary biology. I have subscriptions to science newsletters that arrive several times per week from publications like Science, Nature, Cell, etc., a subscription to Scientific American (Larry doesn't think much of it), lots of books loaned from the library and on my Kindle, and I read various blogs on this area of science and others.

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    5. Your curiosity was exhausted when you settled for sappy answers before you ever started asking serious questions.

      So please share with us the details you have discovered, thru your curiosity, regarding the precise mechanism by which you believe those things have arisen. Beyond "Goddidit", of course. Or at least share some of the findings and research being pursued on that question by creation "scientists" and intelligent design "researchers." Since they're all so, y'know, curious.

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