Intelligent Design

How would a Last Universal Common Ancestor not have gone extinct because of mutations?

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Let’s suppose there was a first Last Universal Common Ancestor (LUCA) or a small population of it. How did it overcome deleterious harmful mutations, in order not to go extinct?  

M.LYNCH (2003): Although uncertainties remain with respect to the form of the mutational-effect distribution, a great deal of evidence from several sources strongly suggests that the overall effects of mutations are to reduce fitness. Indirect evidence comes from asymmetrical responses to artificial selection on life history traits, suggesting that variance for these traits is maintained by downwardly skewed distributions of mutational effects. More direct evidence comes from spontaneous mutation accumulation (MA) experiments in Drosophila, Caenorhabditis elegans, wheat, yeast, Escherichia coli, and different mutation accumulation (MA) experiments in Arabidopsis. All of these experiments detected downward trends in mutation accumulation (MA) line population mean fitness relative to control populations as generations accrued. As far as we know, there is no case of even a single MA line maintained by bottlenecking that showed significantly higher fitness than its contemporary control populations. 2

M.C. Whitlock (2004): The overall effect of mutation on a population is strongly dependent on the population size. A large population has many new mutations in each generation, and therefore the probability is high that it will obtain new favorable mutations. This large population also has effective selection against the bad mutations that occur; deleterious mutations in a large population are kept at a low frequency within a balance between the forces of selection and those of mutation. A population with relatively fewer individuals, however, will have lower fitness on average, not only because fewer beneficial mutations arise, but also because deleterious mutations are more likely to reach high frequencies through random genetic drift. This shift in the balance between fixation of beneficial and deleterious mutations can result in a decline in the fitness of individuals in a small population and, ultimately, may lead to the extinction of that population. As such, a change in population size may determine the ultimate fate of a species affected by anthropogenic change.3

J.C.Sandord (2022): Genetic Entropy is the genetic degeneration of living things.  Genetic entropy is the systematic breakdown of the internal biological information systems that make life alive.  Genetic entropy results from genetic mutations, which are typographical errors in the programming of life (life’s instruction manuals). Mutations systematically erode the information that encodes life’s many essential functions.  Biological information consists of a large set of specifications, and random mutations systematically scramble these specifications – gradually but relentlessly destroying the programming instructions essential to life. Genetic entropy is most easily understood on a personal level. In our bodies there are roughly 3 new mutations (word-processing errors), every cell division. Our cells become more mutant, and more divergent from each other every day. By the time we are old, each of our cells has accumulated tens of thousands of mutations. Mutation accumulation is the primary reason we grow old and die.  This level of genetic entropy is easy to understand. There is another level of genetic entropy that affects us as a population. Because mutations arise in all of our cells, including our reproductive cells, we pass many of our new mutations to our children. So mutations continuously accumulate in the population – with each generation being more mutant than the last. So not only do we undergo genetic degeneration personally, we also are undergoing genetic degeneration as a population. This is essentially evolution going the wrong way. Natural selection can slow down, but cannot stop, genetic entropy on the population level. 

Apart from intelligence, information and information systems always degenerate. This is obviously true in the human realm, but is equally true in the biological realm (contrary to what evolutionists claim).  The more technical definition of entropy, as used by engineers and physicists, is simply a measure of disorder. Technically, apart from any external intervention, all functional systems degenerate, consistently moving from order to disorder (because entropy always increases in any closed system). For the biologist it is more useful to employ the more general use of the word entropy, which conveys that since physical entropy is ever-increasing (disorder is always increasing), therefore there is universal tendency for all biological information systems to degenerate over time – apart from intelligent intervention.1

1. J.C.Sanford: Genetic entropy 2022
2. Michael Lynch: TOWARD A REALISTIC MODEL OF MUTATIONS AFFECTING FITNESS 2003 Mar
3. Michael C. Whitlock: Fixation of New Mutations in Small Populations 2004

24 Replies to “How would a Last Universal Common Ancestor not have gone extinct because of mutations?

  1. 1
    Sandy says:

    Unfortunatelly for sweet LUCA nobody saw him/her/it therefore is just imagination. I mean if we want to talk about science then LUCA is just another fairytale like a multiverse or darwinian evolution.

  2. 2
    bornagain77 says:

    as to the question of “How Would A Last Universal Common Ancestor Not Have Gone Extinct Because Of Mutations?”

    This also reminds me of the ‘mutation protection paradox’,

    Darwinian evolution depends on random ‘mutations/errors’ to DNA in order to give Darwinian evolution a semblance of feasibility. Yet there are multiple layers of error correction that are now found in the cell that protect against “random mutations” happening to DNA.

    Some of the sophisticated and overlapping repair mechanisms found for DNA thus far include, (but are not limited to), the following:

    A proofreading system that catches almost all errors
    A mismatch repair system to back up the proofreading system
    Photoreactivation (light repair)
    Removal of methyl or ethyl groups by O6 – methylguanine methyltransferase
    Base excision repair
    Nucleotide excision repair
    Double-strand DNA break repair
    Recombination repair
    Error-prone bypass 40,,,
    Harmful mutations happen constantly. Without repair mechanisms, life would be very short indeed and might not even get started because mutations often lead to disease, deformity, or death. So even the earliest, “simple” creatures in the evolutionist’s primeval soup or tree of life would have needed a sophisticated repair system. But the (sophisticated repair) mechanisms not only remove harmful mutations from DNA, they would also remove mutations that evolutionists believe build new parts. The evolutionist is stuck with imagining the evolution of (sophisticated repair) mechanisms that prevent evolution, all the way back to the very origin of life.
    http://www.newgeology.us/presentation32.html

    Again, the dependency of Darwinian evolution on random mutations to DNA, and yet the existence of multiple layers of repair mechanisms that prevent random mutations from happening to DNA, has been termed the ‘mutation protection paradox’.

    The Evolutionary Dynamics of Digital and Nucleotide Codes: A Mutation Protection Perspective – February 2011
    Excerpt: “Unbounded random change of nucleotide codes through the accumulation of irreparable, advantageous, code-expanding, inheritable mutations at the level of individual nucleotides, as proposed by evolutionary theory, requires the mutation protection at the level of the individual nucleotides and at the higher levels of the code to be switched off or at least to dysfunction. Dysfunctioning mutation protection, however, is the origin of cancer and hereditary diseases, which reduce the capacity to live and to reproduce. Our mutation protection perspective of the evolutionary dynamics of digital and nucleotide codes thus reveals the presence of a paradox in evolutionary theory between the necessity and the disadvantage of dysfunctioning mutation protection. This mutation protection paradox, which is closely related with the paradox between evolvability and mutational robustness, needs further investigation.”
    https://benthamopen.com/contents/pdf/TOEVOLJ/TOEVOLJ-5-1.pdf

    Contradiction in evolutionary theory – video – (The contradiction between extensive DNA repair mechanisms and the necessity of ‘random mutations/errors’ for Darwinian evolution)
    http://www.youtube.com/watch?v=dzh6Ct5cg1o

    As the following article states, “The bottom line is that repair mechanisms are incompatible with Darwinism in principle. Since sophisticated repair mechanisms do exist in the cell after all, then the thing to discard in the dilemma to avoid the contradiction necessarily is the Darwinist dogma.”

    The Darwinism contradiction of repair systems – 2009
    Excerpt: The bottom line is that repair mechanisms are incompatible with Darwinism in principle. Since sophisticated repair mechanisms do exist in the cell after all, then the thing to discard in the dilemma to avoid the contradiction necessarily is the Darwinist dogma.
    http://www.uncommondescent.com.....r-systems/

    Of supplemental note: the following articles give us a (small) glimpse into just how (very) sophisticated some of these repair mechanisms for DNA actually are,

    A Look at the Quality Control System in the Protein Factory – JonathanM – March 2012
    Excerpt: The DNA damage response (DDR) system is like a cellular special ops force. The moment such damage is detected, an intricate network of communication and recruitment launches into action. If the cellular process for making proteins were a factory, this would be the most advanced quality-control system ever designed.
    http://www.evolutionnews.org/2.....57791.html

    Quantum Dots Spotlight DNA-Repair Proteins in Motion – March 2010
    Excerpt: “How this system works is an important unanswered question in this field,” he said. “It has to be able to identify very small mistakes in a 3-dimensional morass of gene strands. It’s akin to spotting potholes on every street all over the country and getting them fixed before the next rush hour.” Dr. Bennett Van Houten – of note: A bacterium has about 40 team members on its pothole crew. That allows its entire genome to be scanned for errors in 20 minutes, the typical doubling time.,, These smart machines can apparently also interact with other damage control teams if they cannot fix the problem on the spot.
    http://www.sciencedaily.com/re.....123522.htm

    Molecular Machines Are Amazing Alone, but When They Cooperate — Wow! – January 14, 2014
    Excerpt: RNA polymerase — the machine that translates DNA into RNA — is the star player. It patrols the DNA like an automated inspector on train tracks. When it encounters a break, it stops and waits. The problem is, when it stops, it stalls over the break, preventing repair machines from reaching it. Not to worry. Everything is under control.
    In the new study, the NYU School of Medicine researchers reveal how another enzyme called UvrD helicase acts like a train engine to pull the RNA polymerase backwards and expose the broken DNA so a repair crew can get to work….
    The study by Dr. Nudler’s group and colleagues in Russia used a battery of biochemical and genetic experiments to directly link UvrD to RNA polymerase and to demonstrate that UvrD’s pulling activity is essential for DNA repair. The lab results also suggest that UvrD relies on a second factor, called NusA, to help it pull RNA polymerase backwards. Those two partners then recruit a repair crew of other proteins to patch up the exposed DNA tracks before the train-like polymerase continues on its way.
    per evolution news

    Nobel Prize 2015: What the chemistry winners taught us about the fragility of human life – Julia Belluz – October 7, 2015,
    Excerpt: “[DNA] turned out to be photosensitive, temperature sensitive, and all-sorts-of-other-stuff sensitive, and that meant that living cells (1) must have mechanisms to repair DNA damage and (2) must spend a substantial amount of time and energy on them,” explained chemist Derek Lowe in a fantastic blog post on the awards.,,,
    the Nobel Prize Committee said. “It is constantly subjected to assaults from the environment, yet it remains surprisingly intact.”…
    The upshot of these discoveries is that cells are constantly working to repair DNA damage. “Every day, [these processes] 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,” the Nobel Committee described. “Our genome would collapse without these repair mechanisms.”
    These discoveries were important in themselves: They completely changed how the scientific community understood the fundamentals of cell biology and DNA.
    http://www.vox.com/2015/10/7/9.....-about-the

    New class of DNA repair enzyme discovered – October 29, 2015
    Excerpt: The newly discovered DNA repair enzyme is a DNA glycosylase, a family of enzymes discovered by Tomas Lindahl, who received this year’s Nobel prize for recognizing that these enzymes removed damaged DNA bases through a process called base-excision repair. It was the first of about 10 different DNA repair pathways that biologists have identified to date.,,,
    “Our discovery shows that we still have a lot to learn about DNA repair, and that there may be alternative repair pathways yet to be discovered. It certainly shows us that a much broader range of DNA damage can be removed in ways that we didn’t think were possible,” said Eichman
    – per physorg

    Nuclear membrane repairs the ‘dark matter’ of DNA – October 29, 2015
    Excerpt: Previously, the nuclear membrane was thought to be mostly just a protective bubble around the nuclear material, with pores acting as channels to transport molecules in and out. But in a study published on October 26 in Nature Cell Biology, a research team led by Irene Chiolo documents how broken strands of a portion of DNA known as heterochromatin are dragged to the nuclear membrane for repair.
    DNA exists inside of a cell’s nucleus in two forms: euchromatin and heterochromatin. Euchromatin gets all of the attention because it encodes most of the genome, while heterochromatin, which is mostly composed of repeated DNA sequences, has long been ignored as “junk DNA.”
    “Scientists are now starting to pay a lot of attention to this mysterious component of the genome,” said Chiolo, assistant professor at the USC Dornsife College of Letters, Arts and Sciences. “Heterochromatin is not only essential for chromosome maintenance during cell division; it also poses specific threats to genome stability. Heterochromatin is potentially one of the most powerful driving forces for cancer formation, but it is the ‘dark matter’ of the genome. We are just beginning to unravel how repair works here.”
    The reason why we don’t experience thousands of cancers every day in our body is because we have incredibly efficient molecular mechanisms that repair the frequent damages occurring in our DNA. But those that work in heterochromatin are quite extraordinary.,,,
    Working with the fruit fly Drosophila melanogaster, the team observed that breaks in heterochromatin are repaired after damaged sequences move away from the rest of the chromosome to the inner wall of the nuclear membrane. There, a trio of proteins mends the break in a safe environment, where it cannot accidentally get tangled up with incorrect chromosomes.
    per physorg

    The Chromosome in Nuclear Space – Stephen L. Talbott
    Talbott:
    If you arranged the DNA in a human cell linearly, it would extend for nearly two meters. How do you pack all that DNA into a cell nucleus just five or ten millionths of a meter in diameter? According to the usual comparison it’s as if you had to pack 24 miles (40 km) of extremely thin thread into a tennis ball. Moreover, this thread is divided into 46 pieces (individual chromosomes) averaging, in our tennis-ball analogy, over half a mile long. Can it be at all possible not only to pack the chromosomes into the nucleus, but also to keep them from becoming hopelessly entangled?
    Obviously it must be possible, however difficult to conceive — and in fact an endlessly varied packing and unpacking is going on all the time.,,,
    Managing the Twists
    Perhaps none of this helps us greatly to understand how the extraordinarily long chromosome, tremendously compacted to varying degrees along its length, can maintain itself coherently within the functioning cell. But here’s one relevant consideration: there are enzymes called topoisomerases, whose task is to help manage the forces and stresses within chromosomes. Demonstrating a spatial insight and dexterity that might amaze those of us who have struggled to sort out tangled masses of thread, these enzymes manage to make just the right local cuts to the strands in order to relieve strain, allow necessary movement of individual genes or regions of the chromosome, and prevent a hopeless mass of knots.
    Some topoisomerases cut just one of the strands of the double helix, allow it to wind or unwind around the other strand, and then reconnect the severed ends. Other topoisomerases cut both strands, pass a loop of the chromosome through the gap thus created, and then seal the gap again. (Imagine trying this with miles of string crammed into a tennis ball — without tying the string into knots!) I don’t think anyone would claim to have the faintest idea how this is actually managed in a meaningful, overall, contextual sense, although great and fruitful efforts are being made to analyze isolated local forces and “mechanisms”.
    http://natureinstitute.org/txt.....nome_2.htm

    Quote and Verse

    “applying Darwinian principles to problems of this level of complexity is like putting a Band-Aid on a wound caused by an atomic weapon. It’s just not going to work.”
    – David Berlinski

    Psalm 139:13-14
    For you created my inmost being;
    you knit me together in my mother’s womb.
    I praise you because I am fearfully and wonderfully made;
    your works are wonderful,
    I know that full well.

  3. 3
    martin_r says:

    Geneticist Dr. John Sanford and his 2018 presentation on genetic entropy
    for National Institutes of Health.

    During Q & A, he received the following question on living fossils:

    https://youtu.be/2Mfn2upw-O8?t=3463

    The answer might be – perhaps these species are not that old ? :))) or, these species get periodically fixed (like Dr. Sanford suggested, but he was sort of joking)

  4. 4
    martin_r says:

    as to genetic entropy….

    through the years, i debated lots of evolutionists.

    I got schooled, repeatedly, that i don’t understand how evolution works – you know, how good mutations occur and these are selected and after long time of this process, here we (humans) are …

    I asked them, to compare their list of known ‘good mutations’ with my list of known bad mutations.
    Each time, it was a grotesque. Most of them couldn’t think of any good mutations. Some of them were parroting the sickle-cell mutation … and that was it.

    So, Seversky, JVL, Chuck and Co., please let’s compare the list of good mutations with the following list of bad mutations

    from Wikipedia:

    “There are over 6,000 known genetic disorders in humans.”

    https://en.wikipedia.org/wiki/List_of_genetic_disorders

    Now, Seversky and Co, your list…. please ….

  5. 5
    Sandy says:

    Boragain77
    The bottom line is that repair mechanisms are incompatible with Darwinism in principle.

    Functional coded information that is the foundation of life is incompatible with darwinism . If foundation is incompatible then everything that follows is incompatible:signalling,feedback loops,repair, adaptation to maintain homeostasis even the external environment is changing , etc…

  6. 6
    Alan Fox says:

    I’ll be interested to see if any of the more well-known ID proponents pitch in to support Mr Grasso. I’m thinking of Behe, Meyer, Wells, Nelson and so on. That is a choice for them. My prediction is they will studiously fail to notice Mr Grasso’s contributions. Let’s wait and see if I’m right.

  7. 7
    Alan Fox says:

    By all means continue the cheerleading in the meantime. It’s good for morale.

  8. 8
    martin_r says:

    Sandy @5

    The bottom line is that repair mechanisms are incompatible with Darwinism in principle.

    the day Darwinists discovered DNA proofreading/repair mechanism(s), on that day Darwin’s theory of evolution felt apart.

    Any repair has to be engineered. ANY.

    In order to repair something, the following needs to be met:

    1. one has to know that something is broken (DNA damage sensing)

    2. one has to identify where exactly it is broken

    3. one has to know when to repair it (e.g. you have to stop/or put on hold some other ongoing processes, in other words, you need to know lots of other things, you need to know the whole system, otherwise you make more damage…)

    4. one has to know how to repair it (to use the right tools, materials, energy, etc, etc, etc )

    5. and, eventually, you have to make sure that you fixed it OK. (this can be observed in DNA repair as well)

    it is not surprising, that the theory of evolution was developed by natural science graduates who never made anything … these people are naive romantics … i don’t blame them for being naive … i blame them because in 21st century their theory is a direct attack on every engineer. This theory is as offensive as it gets …. and i can’t believe that this is still happening in 21st century …

  9. 9
    bornagain77 says:

    Martin and Sandy, I think you will get kick out of the following findings which, fairly dramatically, underscores your point about needing to know what needs to be repaired, and knowing how to repair it,

    Extreme Genome Repair – 2009
    Excerpt: If its naming had followed, rather than preceded, molecular analyses of its DNA, the extremophile bacterium Deinococcus radiodurans might have been called Lazarus. After shattering of its 3.2 Mb genome into 20–30 kb pieces by desiccation or a high dose of ionizing radiation, D. radiodurans miraculously reassembles its genome such that only 3 hr later fully reconstituted nonrearranged chromosomes are present, and the cells carry on, alive as normal.,,,
    http://www.ncbi.nlm.nih.gov/pm.....MC3319128/

    In the lab, scientists coax E. coli to resist radiation damage – March 17, 2014
    Excerpt: ,,, John R. Battista, a professor of biological sciences at Louisiana State University, showed that E. coli could evolve to resist ionizing radiation by exposing cultures of the bacterium to the highly radioactive isotope cobalt-60. “We blasted the cultures until 99 percent of the bacteria were dead. Then we’d grow up the survivors and blast them again. We did that twenty times,” explains Cox.
    The result were E. coli capable of enduring as much as four orders of magnitude more ionizing radiation, making them similar to Deinococcus radiodurans, a desert-dwelling bacterium found in the 1950s to be remarkably resistant to radiation. That bacterium is capable of surviving more than one thousand times the radiation dose that would kill a human.
    http://www.news.wisc.edu/22641

  10. 10
    relatd says:

    Martin_r at 8,

    “naive romantics”? Too much evidence is posted here that shows they – meaning the usual suspects – will promote evolution regardless of ANY claims to the contrary. Regardless of ANY facts to the contrary. A repair mechanism came about by chance, along with the necessary sensors to identify the problem and along with the necessary repair mechanism to fix the problem.

    No, only a purpose-designed system can do this.

  11. 11
    Otangelo says:

    Since we are talking about paradoxes :

    Peto’s paradox….

    Marc Tollis (2017): In a multicellular organism, cells must go through a cell cycle that includes growth and division. Every time a human cell divides, it must copy its six billion base pairs of DNA, and it inevitably makes some mistakes. These mistakes are called somatic mutations (cells in the body other than sperm and egg cells). Some somatic mutations may occur in genetic pathways that control cell proliferation, DNA repair, apoptosis, telomere erosion, and growth of new blood vessels, disrupting the normal checks on carcinogenesis. If every cell division carries a certain chance that a cancer-causing somatic mutation could occur, then the risk of developing cancer should be a function of the number of cell divisions in an organism’s lifetime. Therefore, large-bodied and long-lived organisms should face a higher lifetime risk of cancer simply due to the fact that their bodies contain more cells and will undergo more cell divisions over the course of their lifespan. However, a 2015 study that compared cancer incidence from zoo necropsy data for 36 mammals found that a higher risk of cancer does not correlate with increased body mass or lifespan. In fact, the evidence suggested that larger long-lived mammals actually get less cancer. This has profound implications for our understanding of how the cancer problem is solved.

    When individuals in populations are exposed to the selective pressure of cancer risk, the population must evolve cancer suppression as an adaptation or else suffer fitness costs and possibly extinction. Discovering the mechanisms underlying these solutions to Peto’s Paradox requires the tools of numerous subfields of biology including genomics, comparative methods, and experiments with cells. For instance, genomic analyses revealed that the African savannah elephant (Loxodonta africana) genome contains 20 copies, or 40 alleles, of the most famous tumor suppressor gene TP53. The human genome contains only one TP53 copy, and two functional TP53 alleles are required for proper checks on cancer progression. When cells become stressed and incur DNA damage, they can either try to repair the DNA or they can undergo apopotosis, or self-destruction. The protein produced by the TP53 gene is necessary to turn on this apoptotic pathway. Humans with one defective TP53 allele have Li Fraumeni syndrome and a ~90% lifetime risk of many cancers, because they cannot properly shut down cells with DNA damage. Meanwhile, experiments revealed that elephant cells exposed to ionizing radiation behave in a manner consistent with what you would expect with all those TP53 copies—they are much more likely to switch on the apoptotic pathway and therefore destroy cells rather than accumulate carcinogenic mutations.

    https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-017-0401-7

    Comment: How does the author explain the origin of these protective mechanisms? He claims: “The solution to Peto’s Paradox is quite simple: evolution”. This is an ad-hoc assertion and raises the question: How could complex multicellular organisms have evolved if these cancer protection mechanisms were not implemented before the transition occurred, since, otherwise, these organisms would have gone extinct? This problem becomes even greater if considering, that animals with large body size supposedly evolved independently many times across the history of life, and, therefore, these mechanisms would have had to be recruited multiple times. The paradox is only solved, if we hypothesize that large animals were created independently by God, and right from the beginning equipped with tumor suppressor mechanisms from the get-go.

    Any take by you, guys, on this one? When did cancer suppressor mechanisms originate? Before multicellularity arose?

  12. 12
    Otangelo says:

    A. B. Williams (2016): The loss of p53 is a major driver of cancer development mainly because, in the absence of this “guardian of the genome,” cells are no longer adequately protected from mutations and genomic aberrations. Intriguingly, the evolutionary occurrence of p53 homologs appears to be associated with multicellularity. With the advent of metazoans, genome maintenance became a specialized task with distinct requirements in germ cells and somatic tissues. With the central importance of p53 in controlling genome instability–driven cancer development, it might not be surprising that p53 controls DNA-damage checkpoints and impacts the activity of various DNA-repair systems. 64

    B. J. Aubrey (2016): The fundamental biological importance of the Tp53 gene family is highlighted by its evolutionary conservation for more than one billion years dating back to the earliest multicellular organisms. The TP53 protein provides essential functions in the cellular response to diverse stresses and safeguards maintenance of genomic integrity, and this is manifest in its critical role in tumor suppression. The importance of Tp53 in tumor prevention is exemplified in human cancer where it is the most frequently detected genetic alteration. This is confirmed in animal models, in which a defective Tp53 gene leads inexorably to cancer development, whereas reinstatement of TP53 function results in regression of established tumors that had been initiated by loss of TP53.

    TP53: Tumor Suppression and Transcriptional Regulation

    Following activation, the TP53 protein functions predominantly as a transcription factor. The TP53 protein forms a homotetramer that binds to specific Tp53 response elements in genomic DNA to direct the transcription of a large number of protein-coding genes. The requirement for TP53 transcriptional activity in tumor suppression has been examined by systematically mutating the transactivation domains of the TP53 protein, rendering it either partially or wholly transcriptionally defective. Importantly, mutations resulting in complete loss of TP53 transcriptional activity ablate its ability to prevent tumor formation, supporting the concept that transcriptional regulation is central to the tumor-suppressor function. TP53-mediated tumor suppression is governed by transcriptional regulation.

    TP53-mediated transcriptional regulation varies according to the type of stress stimulus and type of cell, so that appropriate corrective processes can be implemented. For example, minor DNA damage may institute cell-cycle arrest and activate DNA-repair mechanisms, whereas stronger TP53-activating signals induce senescence or apoptosis. Accordingly, the TP53 transcriptional response varies depending on the nature of the activating signal and the type of cell. The number of known or suspected TP53 target genes has increased into the thousands with dramatic differences in transcriptional responses observed among different cell types, different TP53-inducing stress stimuli, and varying time points following TP53 activation. These studies paint an increasingly complex picture of the modes by which TP53 can regulate gene expression. For example, before TP53 activation, a subset of target genes is transcriptionally repressed by the TP53 protein. More recently appreciated functions of the TP53 protein include widespread binding and modulation of enhancer regions throughout the genome and transcriptional activation of noncoding RNAs. Interestingly, the TP53-activated long noncoding RNA, lincRNA-p21, exerts widespread suppression of gene expression. The list of proposed TP53 target genes is vast and they are known to influence diverse cellular processes, including apoptosis, cell-cycle arrest, senescence, DNA-damage repair, metabolism, and global regulation of gene expression, each of which could potentially contribute to its tumor-suppressor function.

    Todd Riley (2008): The p53 pathway responds to various cellular stress signals (the input) by activating p53 as a transcription factor (increasing its levels and protein modifications) and transcribing a programme of genes (the output) to accomplish a number of functions. Together, these functions prevent errors in the duplication process of a cell that is under stress, and as such the p53 pathway increases the fidelity of cell division and prevents cancers from arising. 63

    K. D. Sullivan (2017): The p53 polypeptide contains several functional domains that work coordinately, in a context-dependent fashion, to achieve DNA binding and transactivation. (the increased rate of gene expression)

    K. Kamagata (2020): Interactions between DNA and DNA-binding proteins play an important role in many essential cellular processes. A key function of the DNA-binding protein p53 is to search for and bind to target sites incorporated in genomic DNA, which triggers transcriptional regulation. How do p53 molecules achieve “rapid” and “accurate” target search in living cells? The genome encompasses DNA sequences that encode genes, and gene editing is the genetic engineering of a specific DNA sequence, including insertion, deletion, modification, and replacement. The main player in genome editing is a type of protein that can bind to DNA, known as DNA-binding proteins. DNA-binding proteins include enzymes, which can cut DNA or ligate two DNA molecules, and transcription factors, which can activate or deactivate gene expression. These proteins are classified into DNA sequence-specific and nonspecific binders.

    The transcription factor p53 can induce multiple tumor suppression functions, such as cell cycle arrest, DNA repair, and apoptosis. p53 is presumed to solve the target search problem by utilizing 3D diffusion, 1D diffusion along DNA, and intersegmental transfer between two DNAs in the cell.

    Comment: This transcription factor p53 actively searches targets in the genome to be expressed. This is a goal-oriented process implemented to activate processes that avoid the origination of cancer. Various players are required that work as a system. It is a team play. The p53 transcription factor has to be able to perform “rapid” and “accurate” target search, recognize it, and bind to the DNA sequence so it can be expressed, but most important, before it can act like a switch commanding “on”, the gene sequences to be expressed must be there, that is, the actors that are recruited to permit DNA repair, or apoptosis (cell death). It is an all-or-nothing business to convey the function to suppress the development and growth of tumors, and consequently, death. In other words, this is an irreducibly complex system where p53 would be functionless unless the actors to act upon were not there.

    63. Brandon J. Aubrey: Tumor-Suppressor Functions of the TP53 Pathway 2016
    64. A.B. Williams: p53 in the DNA-Damage-Repair Process 2016 May; 6

  13. 13
    whistler says:

    Martin_r
    In order to repair something, the following needs to be met:

    1. one has to know that something is broken (DNA damage sensing)

    2. one has to identify where exactly it is broken

    3. one has to know when to repair it (e.g. you have to stop/or put on hold some other ongoing processes, in other words, you need to know lots of other things, you need to know the whole system, otherwise you make more damage…)

    4. one has to know how to repair it (to use the right tools, materials, energy, etc, etc, etc )

    5. and, eventually, you have to make sure that you fixed it OK. (this can be observed in DNA repair as well)

    For all of these stages obviously the cell needs a Main Control Room from which to coordonate all the actions. Where is hidden this Control Room?

    Bornagain77

    “the extremophile bacterium Deinococcus radiodurans might have been called Lazarus. After shattering of its 3.2 Mb genome into 20–30 kb pieces by desiccation or a high dose of ionizing radiation, D. radiodurans miraculously reassembles its genome such that only 3 hr later fully reconstituted nonrearranged chromosomes are present, and the cells carry on, alive as normal”
    http://www.ncbi.nlm.nih.gov/pm…..MC3319128/

    Outstanding. Lazarus.

    Otangelo
    the African savannah elephant (Loxodonta africana) genome contains 20 copies, or 40 alleles, of the most famous tumor suppressor gene TP53. The human genome contains only one TP53 copy, and two functional TP53 alleles are required for proper checks on cancer progression. When cells become stressed and incur DNA damage, they can either try to repair the DNA or they can undergo apopotosis, or self-destruction. The protein produced by the TP53 gene is necessary to turn on this apoptotic pathway. Humans with one defective TP53 allele have Li Fraumeni syndrome and a ~90% lifetime risk of many cancers, because they cannot properly shut down cells with DNA damage.

    Magnificent. TP53.

    PS: After you hear these impressive findings and a darwinist come to preach about random mutations, random chemical reactions in cell ,and chance you start to think: Poor darwinist has bats in the belfry.The lights are on, but no one is home.

  14. 14
    Seversky says:

    Junk DNA.? Most mutations will occur in non-functional regions where they do no harm?

  15. 15
    Seversky says:

    Mutations are random only with respect to fitness.

  16. 16
    Seversky says:

    If Sandford is correct about genetic entropy then how did life get started in the first place? If the rate of decay in the genome is such as to lead inevitably to catastrophic failure then how did complex multicellular organisms ever emerge?

    As a YEC, he should also explain why his Creator should have designed life based on such a fatally flawed system.

  17. 17
    Alan Fox says:

    If Sandford is correct about genetic entropy then how did life get started in the first place?

    And why are Lenski’s twelve tribes still going?

  18. 18
    jerry says:

    Sanford’s ideas always appeared to me as nonsense.

    While there may be detrimental mutations, it only happens in a few and these entities will die off. Meanwhile millions of other entities do not have the mutation and they and their offspring should thrive.

    Maybe I am wrong. But explain why a mutation that is deleterious would spread to all the members of a species.

  19. 19
    bornagain77 says:

    When Darwin’s Foundations Are Crumbling, What Will the (Darwinian) Faithful Do?
    Excerpt: Here’s a summation of the evolutionary picture that has emerged, according to Behe (in his new book “Darwin Devolves”:
    • The large majority of mutations are degradatory, meaning they’re mutations in which the gene is broken or blunted. Genetic information has been lost, not gained.
    • Sometimes the degradation helps an organism survive.
    • When the degradation confers a survival advantage, the mutation spreads throughout the population by natural selection.
    In genetics, a loss of information generally translates into a loss of function, so it might seem counterintuitive to suppose that a degradatory mutation would confer a survival advantage. Behe gives several examples, though, of instances where damaged genes have been shown to aid survival. In the case of the sickle-cell gene, for example, a single amino acid change causes hemoglobin to behave in a way that inhibits growth of the malaria microbe. It’s a loss-of-function mutation, but it confers a survival advantage in malaria-prone regions.
    The upshot of all this is that Darwin was right in believing that natural selection operating on random variations can cause organisms to become adapted to their environments, but he was wrong in believing that the process was constructive. Nowhere has the Darwinian mechanism been shown to build a complex system. It has only been shown to modify an already-existing system, usually in a loss-of-function manner.
    This is significant enough to upend the Darwinian narrative, but it gets worse. The same factors that contribute to adaptation work to prevent a species from evolving much further. Random mutation and natural selection quickly adjust species to their environmental niches, Behe writes, and then they maroon them there. He cites results from the long-running experiment conducted by Michigan State microbiologist Richard Lenski, whose E. coli lineage has surpassed 65,000 generations (equivalent to more than a million years for a large, complex species like humans), as sound evidence that random mutations wreak havoc in a species—and then that havoc gets frozen in place by natural selection.
    Behe sums up his main argument like this: “beneficial degradative mutations will rapidly, relentlessly, unavoidably, outcompete beneficial constructive mutations at every time and population scale.”1 The only Darwinian examples of evolution that have been observed have followed this pattern and resulted in evolutionary dead ends. Darwin devolves.,,,,
    https://salvomag.com/article/salvo49/darwinism-dissembled

  20. 20
    relatd says:

    Ba77,

    A simpler example of adaptation is the sugar beet. Grown in ideal soil and ideal sunlight, it can yield up to 60% sugar. Grown in poor soil and with less light, it yields less.

    A human being can become grossly obese which can increase the risk of health problems. If he loses the weight and goes on a healthy diet, he can avoid health problems.

    Organisms are clearly adaptive. But one type of animal turning into another? Where does the new functional information come from? In a highly integrated system like the human body, any helpful mutation (if such a thing could happen) would have to occur in the right place and be correctly integrated into the system.

  21. 21
    whistler says:

    Seversky
    Mutations are random only with respect to fitness.

    🙂 This darwinist mantra expired. I guess it’s time to learn new ones.
    You didn’t pay attention how many processes anti-randomness take place in the cell and nobody will do that for you.

    Alan Fox

    If Sandford is correct about genetic entropy then how did life get started in the first place?

    And why are Lenski’s twelve tribes still going?

    1. Lenski’s twelve tribes will be no more if they are let in natural environment to compete with uncoddled infidels .
    2. Lenski’s twelve tribes of bacteria evolved into crippled bacteria (I guess some darwinists consider that crippled bacteria are more advanced/evolved than just bacteria ).

    Jerry
    Sanford’s ideas always appeared to me as nonsense.

    Not really. He is as crafty as a fox with 30 years experience in genetics but he doesn’t have God level “experience”. There are many things to be learned about cell but he is closer to the truth than others.
    For example few more hidden/unknown error-repairing( or mapping ) processes that maintain the genome on the survival path would explain why we are not extinct.

  22. 22
    Alan Fox says:

    @ Whistler

    Whilst not the point of the LTEE, it nonetheless clearly demonstrates Sandford’s idea of “genetic entropy” is mistaken.

  23. 23
    Alan Fox says:

    A human being can become grossly obese which can increase the risk of health problems. If he loses the weight and goes on a healthy diet, he can avoid health problems.

    There’s no doubt obesity in humans can be life-threatening. Seems a bit of a non sequitur in this thread, though.

  24. 24
    Alan Fox says:

    Lenski’s twelve tribes of bacteria evolved into crippled bacteria (I guess some darwinists consider that crippled bacteria are more advanced/evolved than just bacteria ).

    I’m sure it’s correct that, returned to an animal’s gut, the current twelve strains would be outcompeted to extinction by “wild” E coli. But what about the reverse.? What would happen if we were to see who would survive in Lenski’s sparse flask environment? Wild-type wipeout is my prediction. In fact, I bet it’s already been tested. Shall we check?

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