Cellular Creativity and the Unselfish Gene

Nah. ID.

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Aslan is not a Tame Lion

isn't that what I said {aIDs}

Nova,A few more things: This is an interesting proposal. Do you have a link to the research that backs up this recommendation? OK, point taken. Simpler organisms have simpler, yet related, immune systems. How else would the more complex immune systems evolve after all? But where does the 'eureka' hypothesis start to apply? What about yeast and other unicellular Eukaryotes, how did they evolve? And you still haven't dealt with bacteria and viruses.Which leads me to this from your second post: I don't mean to be funny here but I really didn't think I'd need to back this statement up. Go to pubmed search 'virus and evolution', knock yourself out. As has been already suggested, try looking for HIV. Influenza and Rhinoviruses are also great examples of how viruses change rapidly. The poliovirus genome has been found to change by 2% in 5 days. How else are the sequences changing if not by mutation and natural selection?Here's another quote from a book (Medical Microbiology), again emphasis added in bold:

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Genetic reassortment and exchange of influenza viruses between humans and animals, producing antigenic shift, periodically introduce new viruses to the human population; mutation and selection, producing antigenic drift, accounts for year-to-year variations in influenza A subtypes

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Exactly how everything else does it: Imperfect replication and natural selection. It's just that viruses have shorter lifecycles and high selective pressure (retroviruses also have a more error prone replication system).

If you haven't gotten the point yet by 'bird flu mania' on the airwaves:(viruses replicate like crazy) X (a high rate of error in replication) = viruses evolve like crazy

Ooook!I followed your link and instructions but unfortunately, the material at the site did not increase my understanding. I tried to read some of the papers but they were obviously written by professional biochemists for professional biochemists, and therefore were largely incomprehensible to me.All I can say is that if viruses have been 'evolving like crazy' for hundreds of millions of years, then they haven't gone very far up the evolutionary ladder for all their effort.In the system I am advocating in this thread, the variability of viruses is due to the circumstance that a new 'strain' is generated by each Eureka event. It is necessary to form a new strain so that the cells of an organism can recognize whether they have, or have not previously received the genetic message present in the protein envelope of the virus.If cells have previously received the message, then the antibodies specific to that strain of virus are already present in the organism, and the virus is encapsulated by antibodies and destroyed by phagocytes before the envelope is opened (ie, before a cell is infected). If, however the strain has not been previously encountered, the antibodies do not ”recognise the label’ and during the time-lag it takes to generate a high concentration of antibodies specific to the new strain, the virus edits the new gene into the genome, regulated by interferon as previously described.Since the ”label’ on each virus must be unique, it is reasonable to speculate that the virus is labeled with a molecule derived from the test gene, which is also new and unique.Viruses are simply the most evolved manifestation of the inter-cellular communication system. They can be thought of as a mobile organelle of the eukaryotic cell that functions as an intercellular gene distribution system. As Keeton quotes from the forward of a textbook on virology:

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A virus is essentially part of a cell. We observe and recognise as viruses those parts independent enough to pass from cell to cell.

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(Keeton, Biological Sciences p.921)
and

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Genes may also be exchanged and recombined when viruses infect cells

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(Lehninger Principles of Biochemistry p.913)

Well they wouldn't seeing as 'evolutionary ladders' are a misconceived concept. Viruses are very well adapted for what they do,i.e. making more virus. Just because you refuse to try to understand the research which shows very clearly that viruses evolve doesn't somehow make it less true.The most recent paper on Bird flu (Ghedin, et al., 2005), in its abstract, says... Your hypothesis is simply an idle day dream unless you can provide something from the literature which suggests there might be even a grain of truth in it or can propose some method to verify or falsify it.TTFN,WKThis message has been edited by Wounded King, 10-21-2005 02:58 AM

I can't help but wonder if you feel that your ability to make such unique and penetrating observations is a benefit of having a mind so uncluttered with facts about biochemistry.

The process that immunocytes use in constructing antibodies has some interesting paralells to those I envisaged for the formation of the test protein by the hypothetical experimenter gene.Immunocytes synthesize immune globulins, which are molecules consisting of two heavy, invariant polypeptid chains that support two light variable polypeptide chains (which are the antigen binding sites).Susumu Tonegawa and his colleagues studied how the variable portion of the immune globulin was synthesized and concluded:

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that immunocytes can select segments of DNA coding for the variable portion of an antibody chain from different and widely separated parts of the cell genome and transpose them to a position next to the gene for the constant region of a given light chain. After the constant and variable sequences are spliced, RNA polymerase then can make a single mRNA molecule to code for the entire light chain.

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(Lehninger p.928)Perhaps the experimenter gene synthesizes the test protein in the same, or a similar way.Nova

So far in this model, random mutations have played no part in the formation and acceptance of genes.Random mutations are, however, the causal origin of the alleles of a gene, and in this role mutations, (whatever their source), play an important part in the evolutionary process.A gene can only be subject to mutation into alleles after it has become part of the genome of an organism.The Theory of Genetic Inheritance explains how the interactions between the various alleles of a gene can give rise to phenotypic variation, but it does not offer any causal explanation of how the gene that mutated into alleles originally came into existence.If the Eureka Hypothesis is correct then cellular experimentation and intercellular gene transmission add genes to the genome one gene at a time.Because an extremely discriminating process selected the new, foundation gene, there is very little probability that a random change to the gene will produce a more efficiency-enhancing protein than the original. Since diploid organisms carry two copies of each gene, the operation of the copy of the foundation gene will be more efficient, and will more or less short-circuit the operation of the less efficient alleles.This may explain the dominance relations of alleles in Inheritance Theory.After cellular experimentation has generated a new gene and the species has accepted it, random mutations generate a class of variant alleles of the gene, acceptable variants being retained through Natural, and Sexual Selection.Thus, while cellular experimentation and intercellular gene transmission supply the foundation genes for variation, random mutations, inheritance, and diploidy increase the range of variation, allowing a greater degree of phenotypic fine-tuning to be exercised by Natural and Sexual Selection.The Eureka Hypothesis is thus complementary to the Theory of Genetic Inheritance.

One of the greatest points of resistance to the acceptance of the Theory of Evolution is the concept that the variation produced by random mutations to the genetic material can give rise to the highly efficient, purposeful, and complex order that is present in all living things, even granted billions of years of Natural Selection.This essay will examine some points where the concept of random mutation weakens the evolutionary argument, and then examine the same points from the viewpoint of Cellular Experimentation and Evolution by Iterative Gene Additions.For a random mutation to be beneficial to a species a number of independent, improbable events must occur:1) A mutation must occur:

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Mutations in real life are very rare events as far as individual organisms are concerned.

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(Lehninger p.921)2) It must not be repaired:

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Both prokaryotic and eukaryotic cells contain enzyme systems capable of correcting replication errors and various forms of damage to DNA caused by hydrolysis or external mutagenic agents, such as ultraviolet and ionizing radiations, as well as deaminating and alkylating agents.

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(Lehninger p.940).3) It must be beneficial:

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A random change in any delicate and intricate mechanism is far more likely to damage it than improve it. Mutagenic changes in genes being random, it is easy to understand why the vast majority of new mutations are deleterious.

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(Keeton p.605)4) A mutation must be present in the sperm or the ovum of the organism the mutation occurred in. If not, the mutation could not be inherited by the next generation. Therefore the mutation must occur in the gametes themselves, or in the lineage of cells that lead to the gamete producing cells of the gonads, at some time during the development of the organism. In humans, the vast majority of cells are somatic cells rather than gametes.This means that even if a mutation occurs, is not repaired, and, against tremendous odds, is actually beneficial, it is far more likely to occur in one of the somatic cells where it would not be heritable.5) Mutations must also occur in a particular sequence. A mutation that forms an enzyme A that catalyses the synthesis of beneficial protein B from precursor proteins C and D will not be useful until after the mutations that formed proteins C and D has occurred.6) The mutated gene is at first confined to one, then to a small number of organisms that make up the population. There are many factors (unrelated to the new improvement) that could potentially cause death before reproduction of the mutated organism. If the mutated organism falls victim to one of these, then the beneficial mutation will be lost and the species will have to wait till it occurs again to have another chance of acquiring the beneficial mutation.A random mutation must successfully negotiate the above six hurdles before it can arise and persist in the genome of a species. While it is easy to imagine this process sometimes occurs, it is difficult to imagine that this process occurs often enough, or is sensitive enough to create the millions of complex and diverse life-forms we see around us with their beautiful arrangements of organs, their mutual interrelationships, and their fantastically intricate cellular and molecular structures and processes.A seventh, and more philosophical problem with evolution via random mutations is that random mutations and Inheritance Theory offer no insight into how new genes initially form.A mutational change alters existing genetic material, but does not add DNA to the chromosome. The simplest metazoan (Trichoplax adhaerens) has the least DNA content of all multicellular organisms. The most complex, (Homo sapiens) has the greatest chromosomal length (99 cm). Evidently, as an organism becomes more highly evolved, it accumulates DNA in its chromosomes. This is not too surprising since one would expect the blueprints for a human to be more voluminous than the DNA blueprints for, say a flatworm. But how do mutations and Natural Selection increase the total length of the chromosome?Each of the above points will now be examined from the viewpoint of Cellular Experimentation and Evolution by Iterative Gene Additions.1b) While random mutations are rare, new proteins generated by cellular experimentation are not. There are in fact an enormous number of new proteins (ie new genes) being tested simultaneously by the cells of any given evolving species. The new proteins are not necessarily slight variations of existing proteins but may be greatly different to any existing protein.2b) The highly precise fidelity of DNA replication, and the intricate repair systems for damaged DNA occur because almost any change to the standard genome of an organism will be detrimental. The standard genome is the tried and trusted foundation from which new experiments are launched. The inevitable errors that occur are capitalized on in the formation and transmission of alleles made possible by diploidly and inheritance.3b) The improbability of discovering a protein that increases cellular efficiency is offset by the enormous number of experiments that are occurring. As noted in my first post, the number of human cells is such that the almost impossible can occur with a relatively high frequency.4b) A Eureka Event can occur, be recognized and selected in any cell, and not just the small proportion of cells associated with reproduction. Because somatic cells vastly outnumber gametes, it is more probable a Eureka Event will occur in a somatic cell than a gamete. The newly selected gene is transmitted to the gametes by intercellular gene transmission.5b) Genetic additions must still occur in sequence, but the number of test proteins makes the discovery of beneficial combinations vastly more probable. For example, assume the test protein of the cell in (5a) is enzyme A, and precursor protein C is already present in the cell. If viral transmission edits precursor protein D into the standard genome, then this particular cell will synthesize beneficial protein B. When the interferon concentration has decreased to a sufficiently low level, the cell producing enzyme A will yell “Eureka!!”, and distribute the DNA blueprints for enzyme A. Thus Eureka Events can initiate a cascade of beneficial gene additions.6b) The Eureka gene is distributed to a significant proportion of the population in a small amount of time via the spread of ”infection’. The death before reproduction (through causes not related to the new gene) of any individual with the gene becomes less significant, since many other individuals already have copies of the new gene.7b) The total chromosome length increases as the organism becomes more complex because each successful incorporation of a new gene requires the splicing into the chromosome of the DNA blueprint for the new protein. Total chromosomal length thus increases with each iterative addition.Analysis of mouse DNA showed that:

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about 10 percent of mouse DNA consists of short lengths of less than 10 base pairs that are repeated millions of times.

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(Lehninger p.825)
This observation is suggestive of, and consistent with an iterative process of gene additions, where a short insertion sequence is spliced onto each incoming gene before incorporation into the genome.Thus the application of the concepts of Cellular Experimentation, and Evolution by Iterative Gene Additions largely eliminates the difficulties generated by random mutations, and provides simple and natural alternative explanations.Nova

It is my understanding that this is false. You gott'em, I gott'em. Good thing too or I guess we'd have a lot more. Instead we only have a few 10's most of the time that get past this. Since we both have from 5 to 100 of them they clearly are not very deleterious. In fact, a lot of observed mutations are neutral; some neutral as to the protein produced and others producing proteins that are equally effective. Probably true. The end result of which is only a few for you and a few for me. Sometimes true. However, there are a lot of different sequences that can lead to different, similar or identical results. So what? This sound so nice. But it carefully leaves out further considerations. Just taking humans we get 60 million plus new attempts a year to produce something different and beneficial in some way.If you are personally incredulous that the evolutionary process can produce the life-forms we see that is fine. But the arguements above are based on incorrect data, false logic and are incomplete. Are you pretending to know something about this? There are, of course, observed mutations that add to the genome. Total duplication of genes being an obvious one.In addition, I didn't know that humans had the most voluminous "blueprints" (which genes are NOT). Do you have a source for this and a better measurement?

You can stop right there. If the error is repaired, then no mutation occured, by definition. I think you've got this backwards. How could a mutation that occured in one somatic cell out of an entire organism ever be beneficial? I mean, maybe I'm the lucky bastard who has a cell that mutates to provide the benefit of being totally invulnerable to bullets, but if that cell is just one skin cell on the inside of my armpit, we're not even going to get to the point where that could be a beneficial trait to have.So, move "has to be in a germ line cell" up the list a bit. Those are the only mutations we're even remotely interested in examining, since those are the only ones that are going to result in selectable phenotypic change. Why is that so hard to imagine? Do you know how often mutations happen when DNA is replicated? No?Well, I do. For mammalian nuclear DNA, it's about 3.5 mutations per billion base pairs. The human genome is roughly 2.9 billion base pairs (Gbp) long, so that's about 6-7 mutations every time a cell divides. Realistically, looking only at gametes, a mammalian organism could pass on somewhere between 5-500 mutations that it did not inherit from either of its parents.Plenty of mutation. Most of it happens to introns (because introns constitute the vast majority of genetic material in humans and other mammals); most of those that happen in an exon don't change the ultimate protein product; those that do usually have no selective influence on the organism; out of the small fraction that are selected on, most are selected against; leaving only the mutations that are selected for.So, right off the bat, we see that fixation of beneficial mutations is not only easy to believe, it's obvious. One generation of a species of organisms means the introduction of literally millions of non-detrimental (mostly neutral) mutations to the gene pool. This is untrue. A very common type of mutation actually extends repeating sequences of nucleotides, thus actually adding to the length of the gene and the chromosome by adding DNA. Logical fallacy - hasty generalization. For instance, the genome of the ameoba is 600 million base pairs long (Mbp). Are we to conclude that amoebas are just over 1/4th as "evolved" as humans? I'd say that's a little generous.Despite an anthrocentric ego that would put humans on the top of the pile, there's no corellation between the advancement or complexity of an organism and the length of its genome. The real explanation for this, I've given above - a common type of mutation duplicates and extends sequences that are already highly repetitive. What you're proposing is interesting - a kind of mutation and selection that occurs on proteins in the environment of the cell - but redundant; mutation and selection acting on organisms is sufficient to account for the history and diversity of life on Earth. Moreover, your model is not consistent with the fairly poor record of life on Earth - the vast, vast majority of species that have ever existed are extinct. Under your model, where organisms have a drastically improved chance of developing exactly the new proteins they need to survive, we would not expect that to be the case. Your model is wrong simply because it would be too successful.

Nova is both right and wrong; the human genome is the longest measured, coming in somewhere around 2.9 Gbp (I've heard as high as 3.1 Gbp, as well.) The common lab mouse comes in second at around 2.6 Gbp.On the other hand, if we compare genes, humans have only 10,000-20,000 genes - less than rice.So, it depends on how you want to look at it. The human genome is a lot like trying to impress your teacher by padding your anemic book report with double-line spacing and nearly-empty chapter title sheets. You might come in at 2.9 billion pages, but if only 1.5% of that is the actual report, in the way that only 1.5% of our genome is has phenotypical function, you're nowhere near the depth of the guy in the next desk with a lot less pages, but a lot more content.

Hi crashfrog Close, but its not that "organisms have a drastically improved chance of developing exactly the new proteins they need to survive".Rather it is that cells have a drastically improved chance of finding and incorporating genes that encode for proteins that decrease cellular inefficiency*.The gene is selected on the basis of cellular efficiency. Whatever phenotypic consequences the new gene has are irrelevant and unknown in the first tier of the selection process. The new gene will, however, immediately increase the energy efficiency of the organism into which it is introduced. This is because whatever energy saving occurred at the cellular level is multiplieded by the number of cells that received the new gene. These organisms therefore do not have to consume as much energy from the environment for the same level of activity as other members of the species without the gene.If the gene, when expressed causes phenotypic variation that reduces an organism's efficiency then organisms without the new gene will out-compete the less efficient carriers of the new gene, and the gene will be eliminated.Therefore to be incorporated into the standard genome, a protein must both decrease cellular inefficiency and it must increase the efficiency of the organism relative to other members of the species that do not have the gene.This would be a tall order, but the first tier of the selection process selects only proteins that decrease cellular inefficiency,and the second tier of selection operates onlyon proteins that have already been selected by the first tier.The first selection process generates what amounts to 'random phenotypic variation', and if the random phenotypic variation happens to cause the possessor to be relatively less efficient, Natural Selection will eliminate the organisms that have recieved the new gene. Close again, but not a 'kind of mutation'. The experimental discovery , selection, and transmission of a gene is a highly controlled cellular activity in which random mutations do not play a part, as I explained in the first essay.* So far in my postings I have been using the phrase 'increase cellular efficiency' but this phrase is somewhat misleading. This is the teleological, purposeful interpretation of what a cell selects for in a Eureka Event.Life is a physical process, and like all physical processes is subject to the Laws of ThermodynamicsA cell does not 'strive' to increase its efficiency; a cell selects test proteins that decrease cellular inefficiency in accordance with the Second Law of Thermodynamics. ”Increasing cellular efficiency’ is observationally equivalent to ”decreasing cellular inefficiency’.The difference between life and most other physical processes is that life decreases its inefficiency by systematically accumulating complexity. The process has been continuing for so long that life has become mind-bogglingly complex while continually decreasing its inefficiency.Nova

Then doesn't the whole system get selected out right away? A gene that encodes these trial genes, or however you want to refer to them, connotes an immediate drop in inefficiency; trial and error is not efficient. The two things I don't understand are1) what the mechanism of selection is; and
2) the mechanism for lateral gene transfer between the cells of an organism. Within the tissues there's a sort of cell heredity, if you want to look at somatic cells as a sort of "population"; but there's limited gene flow between "populations." Cells of one tissue maturation do not give rise to maturations of other tissues; some mature tissue types don't give rise to any cells at all. So all this is stem cell activity? Out-compete how? Out-compete for what?Competition as a selective pressure requires initial conditions that Darwin outlined - each generation must reproduce beyond the carrying capacity of its environment. Otherwise, there's no competition. When cells are replicating beyond the capacity of their environment, we have a term for that - it's called "cancer."Since we observe that cells are not usually cancerous, we know that they're not competing. Rather, normal cells respond to physiological cues that co-ordinate their replication so as not to unfairly draw resources. Less efficient in one single somatic cell? That's not going to cause enough of a physiological change to cause selection. There's nothing to select, there. You misunderstood. By "kind of mutation", I meant to refer to the process of generation of these "test protiens", which as far as I can understand, you believe to be random. Did I literally mean that you were referring to the process of genetic mutation held to be at the heart of scientific evolution? No, of course not. I've understood that much, at least. I think I've got the hang of what you're talking about. "Cellular efficiency" being a sort of catch-all term for the characteristics of a cell and its metabolism that would allow it to take greater or lesser advantage of the resources avaliable to it.But really, what need is there for your model? The capacity of random genetic mutation has been established as sufficient to account, and more importantly, we've actually observed that process in operation. This "experimentor gene" idea has no evidentiary support whatsoever beyond all the data that Darwinian evolution explains much more simply.