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Tuesday, April 05, 2022

Two different views of the history of molecular biology

How can different molecular biologists have such opposite views of the history of their field?

I'm posting links to two papers without comment. One of them is from my friend and colleague Alex Palazzo and the other is from James Shapiro who is not my friend or colleague. Both papers have been published in reputable peer-review journals.

The remarkable thing about these two papers is that they have extremely different views of the history of molecular biology and molecular evolution. It's not uncommon for scientists to have different perspectives but these differences are so far apart that one of them just has to be mostly wrong. You decide.

Palazzo, A.F. and Kejiou, N.S. (2022) Non-Darwinian Molecular Biology. Frontiers in genetics 13:1-13. [doi: 10.3389/fgene.2022.831068]

With the discovery of the double helical structure of DNA, a shift occurred in how biologists investigated questions surrounding cellular processes, such as protein synthesis. Instead of viewing biological activity through the lens of chemical reactions, this new field used biological information to gain a new profound view of how biological systems work. Molecular biologists asked new types of questions that would have been inconceivable to the older generation of researchers, such as how cellular machineries convert inherited biological information into functional molecules like proteins. This new focus on biological information also gave molecular biologists a way to link their findings to concepts developed by genetics and the modern synthesis. However, by the late 1960s this all changed. Elevated rates of mutation, unsustainable genetic loads, and high levels of variation in populations, challenged Darwinian evolution, a central tenant of the modern synthesis, where adaptation was the main driver of evolutionary change. Building on these findings, Motoo Kimura advanced the neutral theory of molecular evolution, which advocates that selection in multicellular eukaryotes is weak and that most genomic changes are neutral and due to random drift. This was further elaborated by Jack King and Thomas Jukes, in their paper “Non-Darwinian Evolution”, where they pointed out that the observed changes seen in proteins and the types of polymorphisms observed in populations only become understandable when we take into account biochemistry and Kimura’s new theory. Fifty years later, most molecular biologists remain unaware of these fundamental advances. Their adaptionist viewpoint fails to explain data collected from new powerful technologies which can detect exceedingly rare biochemical events. For example, high throughput sequencing routinely detects RNA transcripts being produced from almost the entire genome yet are present less than one copy per thousand cells and appear to lack any function. Molecular biologists must now reincorporate ideas from classical biochemistry and absorb modern concepts from molecular evolution, to craft a new lens through which they can evaluate the functionality of transcriptional units, and make sense of our messy, intricate, and complicated genome.


Shapiro, J.A. (2022) What we have learned about evolutionary genome change in the past 7 decades. Biosystems 115-116:104669. [doi: 10.1016/j.biosystems.2022.104669]

Cytogenetics and genomics have completely transformed our understanding of evolutionary genome change since the early 1950s. The point of this paper is to outline some of the empirical findings responsible for that transformation. The discovery of transposable elements (TEs) in maize by McClintock, and their subsequent rediscovery in all forms of life, tell us that organisms have the inherent capacity to evolve dispersed genomic networks encoding complex cellular and multicellular adaptations. Genomic analysis confirms the role of TEs in wiring novel networks at major evolutionary transitions. TEs and other forms of repetitive DNA are also important contributors to genome regions that serve as transcriptional templates for regulatory and other biologically functional noncoding ncRNAs. The many functions documented for ncRNAs shows the concept of abundant “selfish” or “junk” DNA in complex genomes is mistaken. Natural and artificial speciation by interspecific hybridization demonstrates that TEs and other biochemical systems of genome restructuring are subject to rapid activation and can generate changes throughout the genomes of the novel species that emerge. In addition to TEs and hybrid species, cancer cells have taught us important lessons about chromothripsis, chromoplexy and other forms of non-random multisite genome restructuring. In many of these restructured genomes, alternative end-joining processes display the capacities of eukaryotes to generate novel combinations of templated and untemplated DNA sequences at the sites of break repair. Sequence innovation by alternative end-joining is widespread among eukaryotes from single cells to advanced plants and animals. In sum, the cellular and genomic capacities of eukaryotic cells have proven to be capable of executing rapid macroevolutionary change under a variety of conditions.


22 comments :

  1. Shapiro is exactly the type of scientist we had in mind when we wrote "Fifty years later, most molecular biologists remain unaware of these fundamental advances."

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    1. Is Shapiro really exactly one of those and does he even deserve the benefit of doubt? He’s old enough and his not even controversial views have been debunked time and again. Even if he doesn’t follow Larry’s Sandwalk he must have met criticism on conferences or in the process of publishing his natural genetic engineering BS.
      The same is true for guys like Jack Mattick who do not even bother to address legitimate criticism. I don’t know why they behave this way, if it is ignorant or willful behavior, if this is about individual personalities or psychological barriers, if it is group dynamics or financial pressure but this is completely different from Ph.D. students who studied biology without encountering any or outdated training in evolutionary biology who may even come from completely different fields like computer science or physics.

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    2. I reviewed Shapiro's book in 2012 and he responded to my review. He makes it clear in his response that he had read my blog.

      James Shapiro Responds to My Review of His Book

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    3. @Lamark & Sickle cell disease
      Neither Kimura nor Larry deny evolution by natural selection. They just say that most molecular evolution is due to 'neutral' processes.
      Michael

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  2. I guessed right what the two different histories would be. Unfortunately,it wasn't difficult

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  3. James Shapiro is a curious one. I've never really understood where he is across the divide between naturalistic science and intelligent design.

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    1. Me neither. I'm pretty sure that most members of the Third Way of Evolution are sympathetic to religion but the website goes out of its way to deny any association with "inscrutable divine forces or supernatural intervention, whether they are called Creationism, Intelligent Design, or anything else."

      Nevertheless, Shapiro has a record of associating with Intelligent Design Creationists and posting on their website.

      The one thing that's clear is that Shapiro and Denis Noble see themselves as leaders of a crusade and not just as scientists.

      The Third Way of Evolution
      “Is James Shapiro a Design Theorist?”: James Shapiro Replies

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    2. I guess Shapiro and Noble do indeed see themselves as scientists. However, the question if they really are and how many real scientists exist. There are real scientists who concede if they learn one of their ideas was bad or wrong. And then there are those guys who just happen to work in science, work in labs, join seminars, give lectures and go to meetings. I am not sure how many real scientists and how much real science is out there. My experience is that a lot of theatre is involved in the business which may raise the question how much different a meeting of the ENCODE consortium is from the staged Biology Information: New Perspectives scam. In both cases you have believers who cannot know better and those who must be aware of the fact that their views are at least controversial. In both cases they will just ignore anything that may undermine their position and play the educated informed thoughtful scientist and deep thinker.

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    3. I do concede though that I am not sure if I would consider myself a real sientist.

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    4. PS. I must admit that in contrast to the attendants of the BI:NP meeting ENCODE produced valuable though not world changing data.

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  4. I'll just say that if I were in fact convinced that natural genetic engineering was a thing, my first order of research would be to discover how it works. How do cells decide what mutations would be useful? What mechanism focuses these events in places where they would benefit their offspring and, apparently, organize a long-term program of consecutive mutations over millions of years with the end in view from the start?

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    1. Along the same lines: if this marvelous and prescient Natural Genetic Engineering exists in the genome, what keeps it present and fully functional in the face of mutation, in the millions of years between the crises that cause the species to need it?

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    2. Well, obviously, natural genetic engineering keeps natural genetic engineering working. Remember: foresight is one of its important properties.

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  5. I would like to know what Shapiro means by "the role of TEs in wiring novel networks at major evolutionary transitions?" It sounds very impressive, but does he ever explain/document that statement?

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  6. BTW Palazzo and Kejiou made the DI's website https://evolutionnews.org/2022/04/heres-another-defense-of-junk-dna/

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    1. I apologize to them. The Intelligent Design Creationists keep a close eye on my blog so I guess I alerted them to Alex's paper. They shouldn't have been surprised at what they read about sloppy genomes since they've been reading it on my blog and in talk.origins for more than thirty years.

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    2. Denyse O'Leary ("News") at Uncommon Descent has now picked it up from them. She has simply declared loudly that the Titanic of junk DNA had sunk long ago. We ought to be intimidated by this -- she's also the one who knows the truth in advance about all sorts of other things including The God Particle, Dark Matter, String Theory, etc. Who needs particle accelerators when you've got O'Leary?

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  7. I am agnostic about the merits of these arguments and I claim no knowledge in the field. However it is much easier to identify logical errors and gaps. Doing so is usually annoying (to some) and is a minimal advance in knowledge but is essential particularly if relevance is at the root of the hypothesis.
    So here is my annoying skepticism. We know very little about the essential distinction between animate and inanimate world except that it shares the same micro structure (molecular level). Life at all levels exhibits what we term as agency in human terms. So unrelenting pursuit of a goal and only for the individual. The goal is growth or thriving which is achieved for some time but inevitably reverses and fails (death). We can analogize this dynamic systems which constrain entropy.
    Given the complete lack of progress in understanding life it is curious to me why the question is not even minimally examined as possibly competing systems (species). Nothing to do with god, or intelligent design. Is the debate mainly about turf b/c other approaches are extremely hard will likely lead nowhere career wise?

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    1. It is extremely difficult to identify logical errors and gaps in a field if you also claim that you have no knowledge in the field.

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    2. Agree but I would add 'small' before 'logical' to your first sentence. It is not my intent to annoy or even to persuade but to raise something to consider. My knowledge of biology is not zero. It is a superficial understanding of the terms, categories, current debates etc which one could expect of an educated person who has an appreciation for difficulty of complicated systems gained from actual experience. Biology -> personal wellbeing/health is a strong motivator for me. I could provide examples of gaps etc which I consider to be not small but that's not likely to be helpful.
      I read your blog b/c it's food for though and mental pushups for an old brain. I will desist from further posts if you prefer.

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    3. If you are really interested in the origin of life and animate/inanimate differences, I highly recommend the books by Nick Lane, particularly "Life Ascending" and "The Vital Question."

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    4. I have read a couple of Lane's books and some blog posts. Lane writes clearly in a popular style and I found his opinions interesting. But I have not retained any detail recollection beyond the dichotomy views of metabolism vs replication template (RNA in his thesis). He leans to the metabolism side if I recall. As well he describes deep sea vents as possible energy but then EM is energy source regardless of frequency. I was not able to follow his detailed chemical process description b/c I lack knowledge to think of counter proposals.
      At the top level failure to empirically explain why entry into the closed web of life now must be due to either changed environment, changed life forms or life forms changing (closing) the possibility. I have not seen such discussion.
      Maybe you were able to extract more from his opinions which I would be glad to hear.

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