59. Correcting Errors And Repairing Damage


Please Note: This is a preview chapter from Part 2, not yet published. I have put it online to commemorate 70 years since Watson and Crick published their proposed structure of DNA (in April 1953), and also so that the whole cluster of microbiological analogies in Jacob's story of his time in Padam-Aram can be seen. This continues the patterns talked about in Chapters 8, 9, 10, 11, 12 and 13 of the book.

One of the most important things in a cell is the information stored within the DNA molecule. The cell needs this to access the blueprints for proteins and machinery. Preserving this information is therefore one of the cell’s top priorities.
   In the process of human cell division, the cell has to copy all of the 3 billion or so “letters” that make up the human genome. It does this at a very rapid rate, copying as many as 1,000 nucleotides a second, many times faster than a human typist.
   The machinery that copies the genome is called “DNA polymerase.” Due to the nature of the copying process, errors occur at a rate of about 1 every 100,000 nucleotides. This might sound low, but it would result in tens of thousands of mistakes creeping in every time the human genome was duplicated, which would be highly damaging to our offspring.
   However, during duplication of the genome, two error correcting processes virtually eliminate these mistakes. The first is equivalent to proofreading each letter by its shape. If the shape of the letter isn’t right, the copying machinery moves back a little, cuts out the wrong letter, and replaces it with the correct one.
   The second is called “mismatch repair,” where the old and new strands are compared, and incorrectly paired nucleotides are removed and replaced. Taken together, these two processes reduce the error rate to around just one in a billion nucleotides.
   Earlier in this letter I put forward the hypothesis that the account of Jacob’s life with Laban, as told in the book of Genesis, was also meant to serve as a series of analogies for various molecular biological processes. For example, Jacob’s dream of the ladder represented the structure of DNA. His four wives represented the four bases used in DNA, and so on. Remarkably, we can also make parallels in Jacob’s story to the two error correcting processes I have just described.
   When Jacob and his family ran away from Laban, Jacob’s wife Rachel stole her father’s household idols. Laban chased after them, to find out why they had run away and why his idols had been stolen.
   Jacob said to Laban: “With whom you find your gods, he will not live. Before our brothers, identify what is yours with me, and take it to you.” 1 Jacob didn’t know Rachel had stolen the idols. She had hidden them in the saddle basket of the camel, and then sat on them.
   Laban looked in the tent of Jacob, the tent of the two maidservants, and the tents of Rachel and Leah, “and Laban felt all of the tent, but did not find them.” 2 And “he searched, but he did not find the idols.” 3 This could represent the first error correcting mechanism, which uses shape to find the error.
   Jacob got angry, and said to Laban: “What is my error? What is my sin, that you chased after me, that you felt all of my belongings? What have you found, from all of the belongings of your house? Put it here before my brothers and your brothers, and they will correct between the two of us.” 4
   The word here translated “error” can mean error or transgression, and the word “correct” can also mean to reprove, but the Hebrew literally also means to correct. In other words, this would make a good analogy for mismatch repair, the second error correcting mechanism, where both strands are compared, and the new strand is corrected.
   It’s also interesting that idols (teraphim in Hebrew, pronounced “tera-pheem”) would be used to represent errors, and they were stolen by Rachel, who I have previously suggested corresponds to one of the four DNA bases. Most of the creative mechanisms of evolution, which according to theorists are responsible for all life as we know it, are actually based on errors – from mutations, which are primarily copying errors or damage, to duplications, which are often just bigger copying errors. The serendipity wands of translocation and magical steps, as waved by evolutionary theorists, may or may not be based on error, but they are usually based on luck. In evolutionary theory, the idols of luck and error replace YHWH who claims to have created all things.
   Now, a fair question we could ask at this point is: if these microbiological processes were actually designed, why include mechanisms to correct errors? Why not just make the copying process completely accurate in the first place?
   I think there are two good explanations. First, copying has to take place with real molecular machinery, which places natural constraints on the system. A perfect copying system might be possible, but perhaps it would need extra equipment that wouldn’t fit easily into the microscopic space inside a cell.
   Second, and perhaps a more important consideration, is that there are also time constraints. A cell needs to divide in a timely manner, so the organism can grow and survive. An extra error correcting step might increase the accuracy by additional orders of magnitude, or maybe a perfect copying system could be devised, but it could also increase the copying time by several orders of magnitude, severely hampering the growth of the organism and the renewal of its cells. In other words, I suspect the system may already be optimized to be as efficient as possible, within those time and space constraints.
   Errors can also occur when proteins are being produced, but most organisms have processes to ensure only correct proteins are made. In an mRNA sequence, often referred to by biologists as a “transcript,” a stop codon tells the ribosome to stop making the protein chain. But sometimes a mutation or copying error can cause a stop codon to appear too early in the transcript. This could lead to the production of a faulty protein, which may be harmful to the cell.
   However, a process called “nonsense-mediated decay” looks out for transcripts with premature stop codons. Another called “non-stop decay” looks for ones that lack a stop codon altogether, and therefore could get stuck in the ribosome. Yet another called “no-go decay” looks for transcripts that get stalled during the translation process. In each case, the faulty or incorrectly made protein is eliminated, to prevent it from causing cell damage.
   Another type of fault that sometimes happens to a transcript is called “frameshift mutation.” In this, a letter gets accidentally added or deleted. But since transcripts are read by ribosomes in sets of three letters, a letter added or removed will often drastically change the meaning of the sequence, and produce a “nonsense” protein. For example, if we took the sentence THE CAT WAS FED, and added the letter R as a mutation before the letter C in CAT, since ribosomes read three letters at a time, the sentence would now read THE RCA TWA SFE D – which destroys most of the original meaning.
   Remarkably, out of all the possible alternative coding structures that could have been used, the one used primarily in nature minimizes the effect of frameshift mutations. How so? Due to the structure of the genetic code, a frameshift mutation is more likely to result in a stop codon appearing within the transcript, triggering the “nonsense-mediated decay” process so that the faulty protein doesn’t get made. Even the specific choice of stop codons in the human genetic code – UAA, UAG and UGA – have been shown to be optimal for achieving this effect. 5
   The two cells that come about as a result of cell division are usually referred to by biologists as “daughter” cells. Another way that prevents errors from being passed on are called “cell cycle checkpoints.” They stop the cell from dividing until damage, faults or errors have been put right. These checkpoints ensure the daughter cells are preserved from damage.
   For example, when bacteria are exposed to ultraviolet radiation that causes damage to their DNA, this triggers what is called the “SOS response,” which sets about to repair the damage. At the same time, it produces a protein that blocks cell division, so the genome isn’t passed on to the daughter cells until the damage has been repaired.
   In eukaryotic cell division, each daughter cell receives one copy of a duplicated chromosome. Tiny filaments reach out and pull the duplicates to opposite sides, so they end up in different daughter cells. However, if a chromosome isn’t attached properly, a checkpoint signal prevents movement toward the sides. This ensures a potentially damaged genome isn’t passed on to the daughter cells.
   We can find a striking analogy for cell cycle checkpoints in the story of Jacob and Laban. After they had gone through their “error correcting” ritual over the stolen idols, they both agreed to build a mound of stones as a witness between each other, that neither would pass to do harm to the other.
   Laban said to Jacob: “If you mistreat my daughters, and if you take women besides my daughters, no man being with us to see you – God is a witness between me and you.” And again: “Look! this mound, and look! the monument which I have set between me and you. This mound is a witness and the monument is a witness, that I will not pass over this mound to you, and that you will not pass over this mound and this monument to me for bad.” 6
   After this, Laban departed, and angels of God came to Jacob, so he named the place he found himself in Mahanaim, meaning “two camps.” 7 He also divided what he had into two camps.8 This reinforces the idea that, in addition to the plain meaning that Laban was telling Jacob not to abuse his daughters, or God (and angels) would be a witness to it, the mounds they built between each other also represent cell cycle checkpoints, particularly before the division of the cell into two daughter cells, two “camps” as it were.
   These checkpoints prevent the daughters from being “mistreated” in the sense of inheriting a damaged genome; and since I earlier suggested that Jacob’s four wives represented the four DNA bases, taking other women besides these could represent damaging additions to the genetic sequences that are passed on.
   Now, even in the protective environment of the cell nucleus, thousands of nucleotides are damaged in each DNA molecule every day. Water degrades DNA over time, and chemicals and radiation also damage it. However, the cell has several DNA damage response systems. Without them, the genome of an organism would decay rapidly, and life would be impossible to sustain. These systems also tend to initiate a checkpoint which halts cell division until the repairs have been completed.
   In cases where a single strand of the DNA double helix is broken, the cell can perform “base excision repair,” where the damaged nucleotide is removed and DNA polymerase machinery inserts the correct base, which is then chemically “glued” to the rest of the strand.
   When more than one nucleotide needs to be removed, a process called “nucleotide excision repair” can be used, where the damaged section is removed and replaced with the correct sequence. In both cases, the other strand of the double helix is used as the template to identify the correct nucleotides.
   Double-strand breaks, where both strands of the double helix have been broken, tend to be more serious and can even result in the death of the cell. These can be repaired in a process called “homologous recombination.” An undamaged section of similar DNA is used as a template. The damaged and undamaged strands exchange nucleotides, and then any gaps are filled in.
   If this process can’t be used, the broken ends can still be joined together in a process called “non-homologous end-joining.” This almost always involves a loss of information, but at least the cell may still be able to function normally.
   However, if more serious damage to the genome has occurred, the cell is likely to produce faulty proteins and machinery, and become a potential danger to the rest of the organism. In this case, the cell undergoes “apoptosis” or programmed cell death.
   Incidentally, how does the cell know where to find a fault in a molecule consisting of millions or even billions of nucleotides? There are a number of mechanisms it uses, but one is particularly remarkable and worth describing briefly here. It turns out that the DNA molecule can also act like an electrical wire, and electrons can be sent down it in a process called “DNA charge transport.”
   Repair proteins use this system to scan for mutations. They bind to the double helix and slide along it, sending out electrons down the DNA strand like engineers testing the line. If the double helix isn’t damaged, the electron reaches a second repair protein which then leaves the strand. But if there’s a fault, this repair protein doesn’t receive the electron signal and continues moving towards the damaged section.
   With all of these error correcting and damage repair systems, cells clearly work hard to preserve the information they inherit. But this raises two important questions. First, how did the information in DNA molecules survive before these correction and repair systems supposedly evolved? If they really did evolve, there must have been a time when the systems didn’t exist. But error correcting and damage repair are critical for viable genomes to be passed on to future generations of cells.
   The second question is, how can these systems actually evolve in the first place? Think of the engineering wisdom required to design a system that can correct damage to just one nucleotide, as in base excision repair. At the very least, the system would need to be able to detect a fault, latch on to the double helix, cut out the faulty nucleotide, bring along the correct nucleotide, and glue it into place somehow.
   Evolutionary theorists argue that some or all of these functions already existed in some form within the cell, so it’s simply a question of recruiting these existing functions. For example, DNA polymerase, the machine which copies the genome, comes with the ability to cut out and repair an error. Maybe a more general damage repair system evolved from this.
   But the real challenge for evolution is, how do all of the specific proteins and functions needed to perform base excision repair come together to form the new process? How do the proteins involved acquire new address labels, and how do the functions get new instructions? The process can’t evolve in a gradual step by step manner. All of the steps I listed a moment ago need to happen in order to perform base excision repair. If any step is missed out, the repair won’t take place.
   Another intriguing question is, how did the shuffling of nucleotides, which evolution ultimately is, figure out how to send an electron down the DNA spiral, like an engineer testing a signal? And what happened before this system supposedly evolved?
   Besides, an even bigger problem for evolution in general is, systems employed by the cell to protect its DNA molecule from damage and mutations places strong limits on what evolution can actually achieve.
   For a directly relevant analogy, consider the field of “evolutionary programming.” In this field, computer software is actually designed that can evolve programs. In these programs, modules, functions or lines of code can be switched on or off, or shuffled around, in an attempt to find more efficient versions of the program.
   The rules written into the software determine how programs running within the software can evolve. However, the software itself can’t mutate. If bits of the software were to do so, it would begin to fail along with the programs evolving within it. Similarly, the software can’t change the computer’s operating system, which governs what the software can do, without breaking itself.
   In other words, evolving programs are restrained by the software designed to allow them to evolve in the first place; and the software itself is restrained by the computer’s operating system.
   We could compare the genome of an organism to a computer’s operating system, and perhaps also the software in our analogy. Of course, a genome is far more advanced than software that humans write. After all, genomes contain a blueprint for the development of an entire organism, as well as blueprints for complex machinery, control sequences and individual genes.
   The operating system used by cells is also very flexible. Rather than just being limited to switching things on or off, the cell can change how much of a gene is produced. It’s an exquisite network of feedback and control. However, in many ways it operates according to the same principles used by computer programmers.
   Programmers use algorithms, which are sets of instructions to perform an operation or solve a problem, and they use loops to perform an operation until certain criteria are met. These must also be part of the genome’s operating system, so that an organism made up of trillions of complex cells can be built out of code stored in a few billion nucleotides.
   Programmers also use functions and modules, which are pieces of code dedicated to a specific task or sequence of tasks. We might think of genes and control sequences as being similar to these.
   However, just as in evolutionary programming, where the rules of the software restrain how a program can evolve, the error correcting and damage response systems used by cells place limits on what evolution can actually do. These systems actively prevent unauthorized changes to the data in the genome, just as evolutionary programming software can’t allow changes to itself. 9
   Replicating single-celled organisms such as bacteria tend to produce clones, which are copies of themselves. However, in sexually reproducing organisms there is a built-in system that allows for genetic variety. When producing new sperm and egg cells, called “gametes,” genes are selected from the gene pool available to the two mating organisms.
   In a process called “recombination” or “crossing over,” genes between father and mother are exchanged, similar to the damage repair process of homologous recombination, but with a certain amount of randomness. This is a major way in which variations in a population are produced. Checkpoints are also present here too. If the genes to be crossed over aren’t of the same length, the production of gametes is aborted.
   Nature uses this system to produce variety. For example, the finches Charles Darwin observed on the Galapagos Islands had differing sizes of beaks. If hard seeds are all that are available to Darwin’s finches in a particular year, ones with a combination of genes to produce a broad beak will survive, and the population will change to reflect this.
   When food that requires a sharp beak is all that becomes available, finches with a combination of genes producing this beak will become dominant. This is natural selection at work, but nature is only selecting from an already existing gene pool which allows for variety. The creatures remain finches.
   In other words, the sexual reproduction system allows for variation, which may be a major source of speciation, but the mutation protection systems used by cells actively work to prevent mutations, which according to evolutionary theorists is claimed to be the primary source of new functions and features.
   Small-scale evolution is allowed, that changes beak size and shape, through the process of genetic recombination or “crossing over,” but evolution that changes the software or operating system of an organism is actively prevented. In short, small-scale variation is built into the system, while large-scale evolution is blocked.
   Furthermore, these mutation protection systems must have been in place from near the start of life on Earth, so that information in DNA could be preserved in the first place. This means large-scale evolution was blocked from the beginning!
   By now it shouldn’t be entirely surprising that we can also find an analogy for the biological process of crossing over in the story of Jacob. After splitting his camp into two, which represented cell division, Jacob selected a gift for his brother Esau.
   “And he lodged there for the night, and he took a gift for Esau his brother from what had come into his hand: two hundred female goats and twenty male goats, two hundred female sheep and twenty rams, thirty suckling camels and their offspring, forty young cows and ten young bulls, twenty female donkeys and ten colts. And he gave the drove into the hand of his servants, the drove by itself. And he said to his servants: ‘Cross over before me and put an interval between drove and drove.’” 10
   Human genes contain regions called “introns” that don’t code directly for proteins, and they are typically ten times bigger than the coding regions or “exons.” The gift Jacob sent Esau is an analogy for one full human gene, the “two hundred” representing introns and the “twenty” representing exons. The other animals could represent address labels and sequences to mark it as a protein. The gene is treated as one “drove” in the biological process of crossing over, but it is really a collection of smaller “droves” separated by “intervals,” the introns.
   The account continues: “And the gift passed over before him, and he lodged that night in the camp. And he rose that night, and he took his two wives and his two maidservants and his eleven children and he crossed the ford of Jabbok. And he took them and he crossed them over the river, and he crossed over what was his. And Jacob was left alone. And a man wrestled with him until the ascending of the dawn.” 11
   The Hebrew word here translated “ford” means “place of passing,” and is related to the word here translated “crossed” (abr, pronounced “av-air”), which is used three times in the passage to describe crossing or passing over. In other words, the writer really wanted to emphasize the act of crossing over or passing something on. And the name of the river, Jabbok (ibq), contains three of the letters from Jacob’s own name (ioqb), in a recombined order.
   This is also what the “recombination” or “crossing over” biological process is all about. It’s about passing on genes from the parents to the next generation. Jacob is left alone on one side of the river, with his wives on the other, which also matches up with the idea of genes from the father and mother crossing over.
   What about the unusual wrestling match that takes place immediately afterwards? Earlier I pointed out that this can remind us of the switch from thymine to uracil when going from DNA to RNA. However, in the context of biological crossing over, another form of wrestling is involved.
   In normal cells, two copies of a gene are stored, one from the father and one from the mother, and they can be slightly different. These variations of the same gene are called “alleles,” and in the case of recombination, one allele becomes “dominant” and the other “recessive.” The dominant one is expressed, while the other is dormant. One isn’t really stronger than the other, the term just helps to determine which version of the gene gets used and which one gets stored as a backup.
   The system of alleles also places another limit on what evolution can actually do. If genes between father and mother don’t match strongly enough, recombination can’t happen. Incidentally, the “homologous recombination” damage repair system uses the backup gene from the father or mother as a template for repair.
   Jacob’s wrestling match serves as an analogy for the concept of dominant and recessive alleles. In the end, Jacob won. His genes became “dominant.” The account repeatedly tells us this all happened in the night, and the Hebrew word for “the night” (lile, pronounced “lah-yil”) is similar to the word “allele.” Curiously, even the Hebrew word here translated “wrestled” (iabq), which is used only in this account, seems to convey extra meaning. The word is similar to Jacob’s name (ioqb), except the Hebrew equivalent of “a” has become “o” and the “b” and “q” have been swapped. The two words (iabq and ioqb) would make a good analogy for alleles, genes that are structurally similar.
   Let’s briefly recap the main biological analogies I have been able to make from the account of Jacob’s life with Laban. Jacob’s dream of the ladder represents the DNA double helix. The three flocks lying on the well represent DNA as an information storage medium for codons. Jacob’s four wives – Leah, Rachel, Bilhah and Zilpah – represent the four bases of DNA – adenine (A), cytosine (C), guanine (G) and thymine (T). They are paired into purines (A and G) and pyrimidines (C and T), just as Rachel is paired with her maidservant Bilhah and Leah with Zilpah. Jacob’s twelve children also come in pairs, representing a DNA sequence, or as Rachel put it as she named her son Naphtali, “the twistings of God!”
   Jacob’s wages represent the process of “transcription” from DNA to mRNA, and the change from a thymine (T) base in DNA to uracil (U) in RNA. Jacob taking three sticks, peeling the bark, and putting the sticks into the troughs for the flocks to conceive represents the process of “translation,” where the “flock” of mRNA is converted by the ribosome “trough” into a protein. The “sticks” represent amino acids put into the ribosome to “conceive” a protein.
   Jacob putting the stronger of the flock in and leaving the weaker out represents the splicing process where introns (regions of a gene that don’t code for the protein) are left out, and also the biological concept of selection or survival of the fittest. Turning the faces of the flock represents protein folding. His complaint that Laban kept changing his wages ten times represents mutations.
   When Jacob’s family left, Rachel stole Laban’s household idols, and Laban came and felt around in all of their tents, and then Jacob told him to put what he had found before them so it could correct between the two of them. These represent the two error correcting processes used when copying the genome before cell division.
   The mounds Jacob and Laban built as a witness and boundary so they wouldn’t pass to do bad to each other represent cell cycle checkpoints. Jacob then split his camp into two, gave a gift to his brother Esau, crossed his family over the ford of Jabbok, and wrestled with a man – which represent cell division, the exchange of genes in the biological process of crossing over, and dominant and recessive alleles.
   At this point, I would like to make the hopefully obvious observation that this isn’t coincidence or reading into the account. There is only one possible way I could make so many analogies in a story spanning a mere five chapters of the book of Genesis – Jacob’s life with Laban was deliberately orchestrated by YHWH to match up with molecular biological processes.
   God must have known in advance that humans would forget about him over time, as they have always done throughout history, and so he has provided skeptics and atheists thousands of years later with the extraordinary evidence they demand for his existence. This cluster of analogies is, in effect, the Signature of YHWH, the Creator of the heavens and the Earth and the creatures living on it; and he is the God of Jacob.
   This “Signature” also serves as the ultimate error correcting and damage repair process. It corrects the fallacy that these biological processes came about by themselves as a result of endless luck and perpetual errors.

1 Genesis 31:32. 2 Genesis 31:34. 3 Genesis 31:35. 4 Genesis 31:36,37. 5 Naumenko et al, “On the optimality of the standard genetic code: the role of stop codons”, 2007. 6 Genesis 31:50-52. 7 Genesis 32:2. 8 Genesis 32:7. 9 For a deeper discussion of mutation protection systems in the context of evolutionary theory, see DeJong, Degens, “The Evolutionary Dynamics of Digital and Nucleotide Codes: A Mutation Protection Perspective”, The Open Evolution Journal, 2011. 10 Genesis 32:13-16. 11 Genesis 32:21-24.

 

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