26 January 2023

Erich von Daniken (2022) 'Evolution is Wrong. A Radical Approach to the Origin and Transformation of Life'

Erich von Daniken (2022)
'Evolution is Wrong'

I was curious what Erich von Daniken's arguments against evolution are, and how good his knowledge and understanding  of evolution is. Surprisingly,  he gives a reasonably accurate but short account of the discovery of DNA. 

He even mentions Phoebus Levene [4], but writes that Levene used a 'supermicroscope' and that later his discoveries were confirmed with an electron microscope (wrong). He accurately but incompletely describes Chargaff's discoveries and also that Watson & Crick's double helix model was based on Chargaff. Unfortunately, Von Daniken doesn't mention the crucial fact that Chargaff discovered that the amounts of A roughly equal the amounts of T in DNA, and the same holds for C and G. Most importantly, he misses the crucial feature of DNA: AT and CG form pairs. And that's the crux of genetic information. He is often distracted by asides and story telling. On another page he knows that "the order of the four bases" is important and "only certain basic bases fit into the sequence ... Others cannot dock at all" without mentioning AT and CG pairs! So, strictly speaking, he didn't get the most important feature of DNA, but he is close. 

As is often done by non-biologists, he mistakes the concept 'genetic code' for the genome (the total of DNA in a cell or of a species). This is wrong. The genetic code is the way the information in DNA is translated into proteins. That is: how 64 base triplets code for 20 amino acids. And that can be done in a million ways. As a consequence of this misunderstanding he never wonders how DNA works and what it does. He is completely unaware of the fact that the genetic code cannot be derived from biochemical laws. It has an arbitrary character. The genetic code of all life on earth is unique to life on earth. It is not an universal law. And this explains why he doesn't see a problem with aliens injecting DNA in humans. This could only be meaningful if the alien DNA had the same genetic code (in the scientific sense) as life on earth. The smallest difference in the genetic code could create an obstacle. Significant deviations from our genetic code, makes 'injecting alien DNA' pointless, even pathogenic.

Not surprising, he quotes the panspermia theory of Fred Hoyle and Chandra Wickramasinghe, because according to this theory the first DNA came from space. He also fully accepts and defends Intelligent Designer Michael Behe's Darwin's Black Box. In Von Daniken's view Intelligent Design means aliens. Aliens created DNA and had sex with humans. Or something like that.

His description of Darwin is short but factual without any Darwin bashing. He includes an illustration of Darwin's finches (!) in the book. So far so good. But, the only occurrence of the concept of 'natural selection', crucial for Darwin's theory of evolution, is in a quote: "A Scientific Dissent from Darwinism [1] ..."  (Intelligent Design!). I found one occurrence of "Darwin's selection (choice)". That's all. As often happens he uses 'survival of the fittest' in stead of 'natural selection'.

Apart from uncritical acceptation of Michael Behe and the Intelligent Design movement, he manages to refer to Hans-Joachim Zillmer Die Evolutions-Lüge. If you start accusing your opponents of lies, then you stop thinking scientifically. He also uses and quotes from Reinhard Junker, Siegfried Scherer (1998) Evolution, Ein Kritisches Lehrbuch. The book has been criticized thoroughly by evolutionary biologist Gerdien de Jong on this blog [2]. Von Daniken says about the book: "excellent work"!!!  However it is not an evolution textbook as Gerdien de Jong explained. There is no evolution textbook mentioned in Evolution is Wrong. So, he knows 'evolution is wrong', but did not read any of the many professional or popular evolution textbooks. There are hundreds of them! [3]. I recommend the excellent and popular book Jerry A. Coyne (2009) "Why Evolution Is True". This is a very complete overview, but it is not a textbook in the sense that for example the structure of DNA, Mendelian and molecular genetics are explained. If only Von Daniken had read this book, he would have known the arguments and facts in favour of evolution. I think he is able to understand everything in the book provided he takes the trouble to study it carefully. Another example of his one-sided reading habits is the fact that he read Dawkins Der Gotteswahn (The God Delusion) in stead of the famous The Selfish Gene. He would have learned a lot about evolution if he had read it. It is available in German: Das egoistische Gen.

 

Conclusion

I was curious about Von Daniken's knowledge of evolution and DNA in his recent Evolution is wrong. I must conclude that his knowledge is fragmentary; there are some surprising bits of knowledge: Evo-Devo, genetic toolkit, CRISPR, genetic knockout, and some fragments of the history of science, but he misses crucial insights and facts.


Notes

  1. "We are skeptical of claims for the ability of random mutation and natural selection to account for the complexity of life" (Intelligent Design credo)
  2. Gerdien de Jong: Der geist der stets verneint. Weglaten, verkeerd weergeven, verdraaien, misleiden, 15 December 2010. We have created a website devoted to the Junker & Scherer book with a few English abstracts.
  3. I have collected all the current evolution textbooks and introductions to evolution on my webpage Introduction to the evolution literature. I could not find a German translation of Coyne's book, so Daniken has to read it in English!
  4. P. Levene discovered and described all the components of DNA, but Watson and Crick (1953) did not refer to him. This demands an explanation. I have to find out what's going on. [29 Jan 2023]

 

This is a tweetblog: a short blog to report news quickly without all the details of a full review. I have used the KOBO ebook. I discovered today that for the first time I can read my books in the browser, that is in full color! and on my computer screen! (logged in with my KOBO account). All KOBO e-readers are black and white. So, this is a huge step forwards.

I am working on an extended version which will appear on my WDW website.

20 January 2023

Famous Watson-Crick base pairing is by far insufficient for DNA copying fidelity

"Despite its beauty, Watson-Crick complementarity is absolutely insufficient to ensure an acceptable fidelity of replication, even with perfect raw materials.  ... Fortunately, fidelity of nucleotide attachment depends not on complementarity, but on active involvement of DNA polymerases." Kondrashov [1]


These statements changed my thinking about DNA dramatically and definitively. More than Tomas Lindahl did. Perhaps because Kondrashov contrasts replication fidelity so clearly with the A:T and C:G base complementarity.


I always had the idea that A:T and C:G base pairing was the crucial feature of DNA and that it was a necessary and sufficient condition for the double-helix structure, replication, transcription and translation. In a restricted sense this is still true, but it is certainly not the whole story. It is a necessary component of life, but it needs help. Lots of help! In the background hundreds of enzymes are constantly working to correct base mis-pairings and replication errors. Kondrashov gives a detailed description of the known enzymes that are involved.

Don't be mistaken, I still agree with the central importance of DNA in biology: 

"The model of the DNA structure built by James Watson and Francis Crick certainly is one of the central discoveries in twentieth-century biology and the entire history of biology." Eugene Koonin [2].

Just as Mendeleev’s periodic table of elements created a foundation in the science of chemistry, so does the structure of DNA create the foundation of biology. DNA as a carrier of genetic information draws the line between living and non-living systems. With the invention of DNA, evolution took off and created millions of species from the most simple to the most complex. Bacteria are based on DNA. Humans are based on DNA. And everything between is based on DNA. DNA seems to have an unlimited potential.

But again, DNA cannot even 'self-replicate' without enzymes. DNA on its own is just a large non-living chemical macro-molecule. It becomes useful only when it is transcribed and translated into proteins ... with the help of enzymes. DNA needs help. Curiously, it created the help itself! Let me introduce the self-building crane as a metaphor for DNA creating its own helpers:


How to build a crane

How to build a crane? A crane can be built by a second crane. But, how to build that second crane? An ingenious solution is a self-building crane which does away with the second crane requirement. It only needs building blocks. The crane can pick them up, integrate them and it grows. Gradually. Similarly, DNA does not need external help. DNA can copy and repair itself with helper enzymes which are encoded in DNA itself.

 

Why are DNA polymerases needed anyway?


It is not immediately clear from Watson & Crick's model why special enzymes such as DNA-polymerases are needed, since the AT and CG base-pairs are formed naturally and spontaneously. Wrong base pairs are excluded by the base pairing rules. Wrong base pairing, for example A with C or T with G, does not fit in the double helix. So, the strong suggestion is that the base-pairing rules are enough for DNA replication. The fidelity of DNA-replication is completely based on the base pairing rules. 

"It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material " Watson & Crick

In 1953 Watson and Crick had absolutely no idea of the insufficiency of the base-pairing for DNA-replication. Their double-helix DNA structure, base pairing and replication were prime examples of beauty and simplicity. "The idea of errors and repair didn’t occur to them, because it wasn’t thought to be necessary” ! [4]

The fact is that enzymes such a s DNA-polymerase are required. Without DNA-polymerases, DNA-replication would produce a 1000-fold higher error rate.  Without DNA-polymerase, the error rate would be 1% (10-2). With DNA-polymerase the error rate is down to 1 in 100,000 bases (10-5) [1]. That is still too high. Several mechanisms bring the error rate down even further.

 

How could DNA have started life without enzymes?

Rolie Barth wrote in a comment to the previous post: "But still I think that physical and chemical mechanisms might play an important role in keeping DNA-structure and information stable, because DNA storage functioned before repair systems were operational. Logically the latter evolved using functioning genes, isn't it?"

Exactly! Good thinking! If the error rate of DNA replication is so high, how could DNA have been replicated reliably without all those enzymes? A chicken and egg problem:

  1. DNA needs a lot of proofreading and repair enzymes  
  2. these enzymes are encoded in DNA
  3. this makes DNA longer (more complex, more genes, more information)
  4. that means more DNA must be maintained
  5. this requires better and/or more enzymes
  6. etc ...

In other words: Eigen paradox [3]:

The error threshold (or critical mutation rate) is a limit on the number of base pairs a self-replicating molecule may have before mutation will destroy the information in subsequent generations of the molecule.

So, it seems you need a long DNA molecule with many high fidelity replication enzymes encoded in its DNA to produce high fidelity DNA replication. A vicious circle. What came first? But I see no reason why copying fidelity could not be improved in a gradual way step by step. It need not have increased a thousandfold in one step! Under favorable environmental conditions (climate, food) natural selection could improve the proofreading and repair machinery step by step. Furthermore, one doesn't need a separate proofreading enzyme, because DNA polymerase has also proofreading activity [5]. Ultimately, it all depends how many genes and how much junk is in your genome. A genome of 1 million functional base pairs can tolerate an error rate of 1:1,000,000 but a genome of 1 billion functional base pairs will degenerate quickly with the same error rate.

 
Conclusion: the above statement of Kondrashov about the insufficiency of base complementarity was an absolute eye-opener for me. My view of DNA as the perfect solution to the problem of heredity was shattered. Lindahl gave the first blow. But I was only really blown away by Kondrashov's statement. For me it is nothing less than a paradigm change.

Yes, DNA is the biggest revolution in biology, and yes, Watson & Crick got it right, but: (1) despite Watson & Crick, DNA replication fidelity is too low without the help of enzymes, (2) this requirement immediately creates a problem for the evolution of complex life based on DNA. In a future blog a will deal with that!

 

 

Notes

  1. Chapter 5 'Struggle for Fidelity', in: Kondrashov, 2017, Crumbling Genome.
  2. Eugene Koonin (2011) The Logic of Chance, p.21 hardback.
  3. Geen leven zonder DNA-repair. De Lindahl paradox en de Eigen paradox. (blog 21 October 2015) (Dutch). See Wikipedia article: Error threshold.
  4.  According to Phil Hanawaltin in the New Scientist: Running repair keeps DNA in order, 15 March 2003.
  5. see wikipedia article DNA polymerase: DNA polymerase with proofreading ability.

 

Further Reading

"Besides base excision repair, nucleotide excision repair, and mismatch repair, there are several other mechanisms that maintain our DNA. Every day, they fix thousands of occurrences of DNA damage caused by the sun, cigarette smoke or other genotoxic substances; they continuously counteract spontaneous alterations to DNA and, for each cell division, mismatch repair corrects some thousand mismatches. Our genome would collapse without these repair mechanisms."

 

13 January 2023

Non-Watson-Crick base pairs that you won't find in the textbooks and Wikipedia

(Continued from previous blog). Yesterday, I found 'officially forbidden' non-Watson-Crick CA and TG base pairs on the website of Nature Scitable. The standard Watson-Crick base pairs are AT and CG. They are in all the textbooks. But, you won't find the non-Watson-Crick base-pairs in the textbooks. Certainly not in this detail. The first figure (a) gives the 4 bases and their rare (tautomeric) forms. They are not in the textbooks. They are apparently in a chemical equilibrium (see arrows). The rare forms are indeed rare, but apparently they do exist. So, we should know about them.

Left: common, Right: rare tautomeric forms of the 4 bases
©Nature Scitable


Standard Watson-Crick base pairs
©Nature Scitable


All 4 bases A, T, C, G have rare forms. But only rare-C and rare-G participate in base pairs, see figure (c). The pairs consists of a common and a rare base. Note that rare-A and rare-T do not participate in rare base pairs:

Rare matching base pairs CA and TG
©Nature Scitable [1]

If this is not confusing enough, on the same webpage Nature shows aberrant base pairing of the bases in their 'normal' form:

Non-Watson-Crick base pairs TG and CA.
©Nature Scitable

My conclusion is that Evolution textbooks and Wikipedia [6] give an incomplete picture of which base pairs are possible in DNA. They do tell about mutation and base pair mismatch, but never show non-Watson-Crick base pairs. I think they should do so. This is an extremely important point: how can you explain mutation to students, if rare base forms and rare base pairs do not exist? Then, show them! If DNA would replicate exclusively on the basis of the standard Watson-Crick base pair rule, then DNA would be copied with 100% reliability eternally. I think, one cannot blame polymerase for copying errors, because polymerase can't enforce chemically impossible base pairing.

Secondly, students get the wrong impression that DNA is a perfect molecule, that bases always follow the Watson-Crick rule, and that DNA is fine-tuned for life. It is an intrinsic property of the bases that they have rare (tautomeric) forms and that they can pair in a non-standard way. 

Hubert Yockey 1992


The question remains: How often do non-Watson-Crick base pairs occur in DNA?  Surprisingly, I found in an aside on page 300 of Hubert Yockey [2] that "the probability that adenine will mispair to cytosine is about 10-4 x 10-4 = 10-8." (AC pair). That is very small. About the CG pair he writes: "...the base selected has a probability of about 10-4 of being in the imino or enol tautometirc form that leads to mispairing." 

He doesn't do anything with these calculations. However, if I understand him correctly, this means that there is a 1 in 10,000 probability that the C or G base is in the wrong form. This would mean that at every replication round of our genome of 3.2 billion bases, 320,000 C or G bases would mispair. Considering that the human body starting from a zygote experiences about 10 quadrillion (1015) cell divisions in a lifetime [3] then the unimaginable number of 3,2 x 1020 C or G base mismatches would occur [4]. The proofreading and repair system has the task to repair these mutations...

Anyhow, it is clear by now that DNA as a carrier of hereditary information is far from perfect [5]. A perfectly intelligently designed DNA would be stable, have bases without tautomers, 100% replication fidelity, didn't need proofreading and repair and didn't have accumulation of DNA damage during aging. No cancer and no genetic diseases as a result! Mutations would only be positive and introduced deliberately as an adaptation to changing environmental conditions.

In the next blog I will return to Kondrashov!


Correction

I was informed that on the Dutch wikipedia page Kwantumbiologie tautomerism is mentioned and illustrated with AT base pair mutating in to an AC base pair. On that page one finds interesting references to the English literature! [24 Jan 2023]


Notes

  1. This illustration is also present in H F Judson The Eighth Day of Creation, page 434 (not a textbook!)
  2. Hubert Yockey (1992) Information theory and molecular biology, hardback Cambridge University Press, page 300. (not an evolution textbook). I have a review of the book on my WDW website.
  3. Wikipedia article cell division (13 Jan 23), but the meaning of quadrillion differs!
  4. In fact 3,2 billion base pairs is the haploid number, but our body cells are diploid so the number should be 6,4 billion! That is the amount of DNA that has to be replicated! And both C and G could be in the wrong tautomeric form, so multiply the number by two.
  5. Fazale Rana (2022) DNA’s Fine-Tuned Structure Minimizes Harmful TautomersReasons to Believe. This is a perfect example of a christian/Intelligent designer who claims that DNA’s optimized structure is evidence for the intelligent design of DNA. He does not show any mismatch base pairs such as the Nature Scitable page does. He does not  deny that base tautomers exist, and that tautomeric forms are harmful and trigger mutations, but claims that it could be worse! Read the article, and draw your own conclusion!
  6. The Wikipedia article Base pair doesn't mention tautomerism, let alone showing illustrations of base mispairs. The Wikipedia article DNA doesn't mention tautomerism. On the page Tautomer DNA is not mentioned at all, although "nucleobases guanine, thymine, and cytosine" are present, but strangely adenine is absent on that page! Wikipedia is really incomplete in this respect. Later I found the Wikipedia article Non-canonical base pairing, ... but the DNA article does not contain a link to this article. The DNA article however, does contain a paragraph 'Non-canonical bases', but that is not the same as non-canonical base pairing! Wikipedia is like loose sand:  a badly-integrated, disjointed system. There is no supervisor who takes care of the coherence of the whole system. This can be expected from a multi-author encyclopedia. [15 Jan 2023] [23 Jan 2023]


05 January 2023

Two Nobel Prizes contradicting each other: Watson and Crick versus Tomas Lindahl

In 1962 Watson, Crick and Wilkins received the Nobel Prize for the discovery of the structure of DNA. In 2015, Tomas Lindahl received the Nobel Prize for the discovery of DNA repair. The first prize symbolizes the beauty of the DNA molecule. The second Nobel Prize symbolizes the weaknesses of the same molecule. So, in a sense, these prizes contradict each other.


Watson-Crick versus Lindahl

How the beauty of DNA (and the Nobel Prize?) blinded scientists for the weaknesses of DNA. Surprise: later those weaknesses were awarded a Nobel Prize!

Why is DNA perfect? Because DNA structure has been proven chemically correct and because the structure gives for the first time a satisfactory explanation of heredity in the biological world. Two problems solved at once. Heredity requires a a stable structure. Since all life forms from bacteria to humans are based on DNA, and life is some 3 billion years old, DNA simply must be a stable structure.

But then came Swedish scientist Tomas Lindahl. He showed that the apparent stability of DNA is not based on its structure, but –totally unexpected – on enzymatic repair and proofreading! So, DNA only seemed stable. But when he started his research, repair-enzymes were unknown. Clearly, his idea contradicted known facts. To see how it could be that all biologists were blinded by the beauty and the logic of DNA, we must first look at some details of DNA structure. Here, I follow the description of Francis Crick in What Mad Pursuit (1988).

In 1950, three years before the discovery of the structure of DNA, chemist Chargaff had found in DNA from many different species the amount of base A equaled the amount of T and the amount of C equaled the amount of G. The relative amounts of AT and CG in species differ. Chargaff did not conclude anything from his data about the structure of DNA. For Watson and Crick it was crucial evidence for AT and CG base pairing. Furthermore, AT and CG base pairs have equal dimensions. So they fit perfectly in a regular double helix. This is important for a very long molecule. Furthermore, to fit in the double helix the four bases have to be in the correct tautomeric form [1]. The beauty of the DNA model is that the specificity of base pairing gives a mechanism for replication (making a copy of DNA). This is a crucial function in biology (cell division, heredity!). Base pairing guaranties an exact copy of a DNA string. So, a crucial biological property is explained with an elegant chemical structure and its properties. "This base pairing is the key feature of the structure [of DNA]" (Crick, 1988, p.166).

One problem remains: a mutation implies that a wrong base is incorporated, but how can mutations occur if base-pairing is always correct? In their second paper in Nature, Watson and Crick wrote: 

"We believe that the bases will be present almost entirely in their most probable tautomeric forms." ... "spontaneous mutation may be due to a base occasionally occurring in one of its less likely tautomeric forms." [2]

So, they explained mutation theoretically and in principle, but had no data about how often the bases were in the 'correct' or 'wrong' tautomeric form [4], [6]. Consequently, they had no idea how often spontaneous mutation occurs. Neither did they seem to care. They simply assumed it occurs in negligible frequencies. They ignored the problem. It apparently did not invalidate the structure as a carrier of hereditary information.

In the years after 1953 scientists were busy with experimental validation of the double helix model. This took some time. Furthermore, solving the genetic code (how the DNA code is translated into proteins) took some hard work too. The solution of these two problems created a solid foundation of molecular biology. It was a tremendous breakthrough. In fact it was a solid foundation for the whole of biological science including evolutionary biology. It seemed no important problems remained. Crick wanted to move on to other fields of research! 

But, than came Lindahl: 

"It was at the time a far-fetched idea that DNA might be unstable in the cellular environment. (Lindahl Nobel lecture )

Tomas Lindahl discovered the intrinsic fragility of DNA. This constituted no less than a paradigm shift. For example: could anyone predict on the basis of the structure of DNA that Uracil could be present in DNA? (it normally occurs only in RNA!). That specific enzymes exist that continuously scan DNA for the presence of Uracil? Also: oxidative damage (see Lindahl Nobel Prize lecture). Water is a damaging agent for DNA! For a complete overview see the Wikipedia article about the endogenous causes of DNA damage.

Thirty five years after the discovery of the double helix and twenty six years after the Nobel Prize, Francis Crick published What Mad Pursuit (1988). By that time Lindahl had already published several papers demonstrating DNA-repair enzymes, his first in 1974. Surprisingly, I found only 1 page about DNA error-correction [3] in What Mad Pursuit. Not important enough? It did not fit in his DNA-is-perfect-paradigm? Yes, Crick knew very well mutations exist. He did experimental work with phage mutants. The mutations he studied were created with chemical mutagens (acridine, proflavin). So, the damage came from outside DNA, not from the inside. It wasn't spontaneous damage. Those mutations were not a threat to the DNA-is-perfect-paradigm. But Lindahl showed that DNA is inherently unstable in its normal cellular environment. Certainly a revolutionary idea. The reason must be clear by now: DNA must be reliable to function as a carrier of genetic information. Evolution produced complex beings such as humans. How much evidence do you need?

Summary 

Life exists - so DNA must be stable

Life exists - so DNA must be repairable

Watson, Crick, and Wilkins received the Nobel Prize for the structure of DNA. Although they did not explicitly claim DNA is stable, it is implicit in the statement that DNA is the carrier of hereditary information and the structure explains why this is the case. The Nobel Prize in Chemistry 2015 was awarded to Tomas Lindahl, Paul Modrich and Aziz Sancar for DNA repair. Repair implies DNA on its own is not a stable molecule. Although the Watson-Crick model is not refuted, its assumed stability certainly has been refuted. I didn't find this contradiction clearly in the literature [5]. I wrote this blog because it is worth pointing out.

In a next blog I will reveal important consequences of the stability/instability of DNA. This blog resulted from shocking remarks in Kondrashov (2017) Crumbling Genome (see previous blog).

 

Notes

  1. Tautomerism is a dynamic equilibrium between two compounds with same molecular formula. Crick did not elaborate on the frequency of right/wrong tautomeric forms of the bases. In his What Mad Pursuit he writes that "Jerry Donohue, who shared an office with us, told us that some of the textbook formulas were erroneous and that each base occurred almost exclusively in one particular form." (p.65). (Which from?). Please note: "almost exclusively"!
  2. Watson, Crick (1953) Genetical Implications of the Structure of Deoxyribonucleic Acid, Nature, May 1953. This is the second publication of Watson and Crick.
  3. and a rough estimate about error-rate. I will return to that in a next blog. 
  4. It seems there are no data and there is no theory to predict the frequency of wrong base tautomeres after 70 years! See:  "calculating the position of tautomeric equilibria in nucleobases is certainly within the grasp of contemporary quantum chemistry, and semi-empirical parameters on which the positions of these equilibria might most sensitively depend could presumably be identified." page 354 in Fitness of the Cosmos for Life. CUP 2008 [added: 9 Jan 2023
  5. Intelligent Design theorist Michael Denton (1998) triumphantly claims that DNA is a remarkably stable structure! I added a paragraph to my review of his Nature's Destiny. How the Laws of Biology reveal Purpose in the Universe on my DWD website. [added: 10 Jan 2023]
  6. Hubert Yockey (1992) is the first author where I found a probability of mispairing of the AT and CG base pairs. In an aside on page 300 he calculates that "the probability that adenine will mispair to cytosine is about 10-4 x 10-4 = 10-8." About the CG pair he writes: "...the base selected has a probability of about 10-4 of being in the imino or enol tautometirc form that leads to mispairing."  (see: keto–enol tautomerism). [added: 11 Jan 2023]

 

 

Further Reading