Home » Intelligent Design » Yet another feather in natural selection’s cap — now Boolean logic! What hasn’t NS accomplished?

Yet another feather in natural selection’s cap — now Boolean logic! What hasn’t NS accomplished?

Mutations Change the Boolean Logic of Gene Regulation
Richard Robinson

DOI: 10.1371/journal.pbio.0040064

Published: March 28, 2006

It is easy to think of a gene acting like a light bulb, switching either on or off, remaining silent, or being transcribed by the RNA-making machinery. The region of DNA that controls the gene’s output is called its regulatory region, and in this simple (and too simplistic) scenario, that region would act like a simple on–off switch.

But the regulatory regions of real genes are more complex, and act more like molecular computers, combining the effects of multiple inputs and calibrating the gene’s output accordingly. The inputs are the various molecules that affect gene activity by binding to sites in the regulatory region. These molecules combine their effects in complex ways. Sometimes the gene remains silent unless both are present. Sometimes they are additive, such that the output when two factors are present is twice the output when only one is present. Sometimes they cancel each other out—in the presence of either, the gene is transcribed, but in the presence of both, it is not.

Thus, the regulatory region acts as a Boolean logic function, whose simple ANDs, ORs, and NOTs combine to determine the output of the gene. In a new study, Avi Mayo, Uri Alon, and colleagues show that mutations in the regulatory region affect this logic function in a simple and well-studied genetic system, the lac operon in Escherichia coli bacteria, whose suite of genes regulate metabolism of lactose.

The authors began by creating multiple strains of bacteria with mutations in the binding sites for the two regulators of the gene, called CRP and LacI, that respond to cyclic AMP and IPTG, an analog of lactose. They analyzed the effect of these mutations on the rate of gene transcription in the presence of varying concentrations of the two inducers. Previously, the authors showed that the function of the unmutated regulatory region was intermediate between a pure “AND gate” (in Boolean parlance) and a pure “OR gate”: that is, at certain concentrations the first regulator AND the second were needed, but at others, one OR the other sufficed. In the mutated strains, they found that some mutations replicated this behavior, while others switched the regulatory region to a more purely AND or purely OR gate, independent of concentration. Some mutations left the regulator almost like a simple light switch, whose on-or-off state depended almost entirely on one, but not the other, regulator.

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21 Responses to Yet another feather in natural selection’s cap — now Boolean logic! What hasn’t NS accomplished?

  1. I have to really laugh at the naivety of the thinking not long ago that genes were everything and the rest was junk. Coding genes are just the tip of the iceberg. In reverse engineering of software, which I’ve done an awful lot of and was a world class expert at, there are easy parts and difficult parts. Reverse engineering the genome proceeds along the same lines. The easy part was the coding genes as there’s a simple lookup table (the genetic code) they follow in specifying amino acid sequences. Once Crick discovered the code we essentially got a free ride in decrypting a fraction of the genome. However that was the easy fraction. In reverse engineering of software this is like pulling out all the ascii strings. They’re easy to recognize as they spell out meaningful things in english, just like genes spell out proteins with known functions. Once you pull out the ascii strings you can then identify the subroutines which point to them and have some idea of what the subroutines are doing because of the string they reference. It starts getting harder there because the subroutines are no longer in english – they’re in machine language. In reverse engineering of software we have the advantage of knowing the machine language but it’s STILL difficult untangling the logic to deduce precise functionality. In the genome, we’re just getting the first glimmers of the machine language and it’s likely to be hideously more complex than any human engineered software and fungible yet malleable from gene to gene and organism to organism. It also appears to be highly fault tolerant. Changing random bits in human engineered software will bring it crashing down most riki tik. In an organism as complex as a person, changing random bits of genetic code often goes unnoticed as the modified function remains close enough to the original to let the organism live a relatively normal life. Not every time of course but surprisingly often. This doesn’t mean the modified bit was junk, it just means we don’t understand how the change subtly effected function. In software reverse engineering there’s often code we find that is never observed executing because we haven’t triggered whatever it is that it does. Sometimes these are functions we haven’t exercised as circumstances haven’t required their use and often they are error recovery routines and we haven’t encountered that error yet. And sometimes it’s just a forgotten bit of code from the past that is still hanging around but is never executed in any circumstance and is termed unexcutable (true junk). Better maintained software is periodically purged of unexcutable code. Genomic equivalents for all these are almost certainties.

    One notable thing remains true. The more of the genome we manage to reverse engineer, the more complex we find it to be. The more complex it is the more unlikely the ability of time and chance to have managed the organizational feat. Of course the tipping point where molecular scale complexity in living things became obviously too much for time and chance to account for was 40 years ago for the more astute and objective among us. For those with a vested interest in not looking like morons for believing the simplistic Darwinian time and chance fairy tale the tipping point hasn’t been reached yet but it’s nearing a bursting point. The more informed boys still clinging to it have a liberty bell of cognitive dissonance ringing in their cranial cavities as we speak. They either reach a tipping point, accept where it leads to quiet the bell, or go nuts. I think it’s too late for some of them and they’ve taken the road less travelled. Their only hope of a normal life from here is through the world of modern mind-manipulating pharmaceuticals to help them cope with a reality that doesn’t fit their fixed mental model of reality i.e. cognitive dissonance. These poor souls will become relics of a mistaken past they cannot part with. Pitiable eccentrics clinging to the genetic equivalent of a flat earth theory. Genomic Luddites. A rotten shame really as many of them are otherwise fairly bright people that might have contributed something useful to the world if they’d just swallowed their pride and admitted their error.

  2. DaveScott: I have to really laugh at the naivety of the thinking not long ago that genes were everything and the rest was junk.

    The man who coined the term “junk DNA”, Susumu Ohno, didn’t believe that non-coding DNA was useless, but rather posited it as a resource for evolutionary experimentation, i.e. junk not trash. As much non-coding DNA is evolutionarily conserved, other hypotheses have been advanced and the search for evidence is ongoing.

    “The noncoding component of the human genome is receiving increased attention from biologists because of its predicted role in regulation of transcription, DNA replication, chromosome pairing, and chromosome condensation.”
    http://www.genome.org/cgi/content/full/11/10/1617

    “Predicted” sounds like a bit of revisionist history to me. I’ve been following this closely for over 30 years now. Junk really meant junk when the term was coined. It’s only in the last decade that the prevailing attitude has been changing. Here’s Nobel winning geneticist Walter Gilbert of Harvard talking about prevailing thought in this 1994 NYT article: Keys Emerge To Mystery Of ‘Junk’ DNA By NATALIE ANGIER Published: June 28, 1994

    “I don’t believe in junk DNA,” said Dr. Walter Gilbert of Harvard University, a pre-eminent theoretician of the human genome. “I’ve long believed that the attitude that all information is contained in the coding regions is very shortsighted, reflecting a protein chemist’s bias of looking at DNA.” Coding regions may make the proteins that are dear to a chemist’s heart; but true biologists, he added, know that much of the exquisite control over these proteins is held offstage, nested within the noncoding junk.

  3. “A rotten shame really as many of them are otherwise fairly bright people that might have contributed something useful to the world if they’d just swallowed their pride and admitted their error.”

    This makes me wonder: suppose that some event causes all evolutionists to wake up tomorrow with their pride in their stomachs and as supporters of ID. No more ‘genomic luddites’.

    Now what?

    How would their day to day research change? What research programs would they initiate that they aren’t following now? How would the paper that’s referred to in the original post be written differently? I’m curious about what the practical effects would be if scientists adopted ID.

    Give me a concrete example of what you mean by an “evolutionist” research program. I’m curious about what practical benefits there are in any “evolutionist” research programs to begin with. My opinion is that there is no practical benefit that comes from presuming that bacteria somehow morphed into mammals via time & chance and constructing phylogenetic trees with everything placed just-so in a presumably historically accurate manner has no practical benefit either. -ds

  4. DaveScot, you’re a genius and technically qualified to comment while I am not. But I’ll take an intuitive stab at this. Creating a mutation to prove what random natural selection is capable of doing is contradictory. Wouldn’t one need to prove this hypothesis by observing evidence that already exists in a natural state?

    Intuition is the highest form of thought. Without it we’d be plodding predictable calculating machines. Your intuition is serving you well in this case I think. Artificial mutations are tests only. The proof of the pudding in whether nature actually works the same way as the in vitro tests indicate is always by confirmation in a natural setting. Sometimes it’s difficult or impossible to do this and that’s the bane of the study of evolution in the distant past. It attempts to reconstruct unwitnessed, unrepeatable events in the remote past where most of the physical evidence has been long destroyed and nothing remains but imprints in rocks. It’s 9 parts speculation and 1 part observation. Not to be confused with experimental biology which is the study of living tissue where speculation can be confirmed by observation and experiment.-ds

  5. I wonder if RM/NS can prove NP is P…

  6. For those interested, I wrote about how complex logic inhibits evolutionary potential a little while back. The introduction is YEC-specific, but the rest is applicable to anyone evaluating the algorithmic potential for change in biological systems.

  7. DaveScot said: “Give me a concrete example of what you mean by an “evolutionist” research program. I’m curious about what practical benefits there are in any “evolutionist” research programs to begin with.”

    I’m not claiming that there is an evolutionist research program. In fact, I’m willing to assume arguendo that there is not. But my question was about what would change on a practical level if all the supporters of evolution were to wake up tomorrow as ID supporters.

    One practical benefit is they wouldn’t have to waste time trying to gratuitously fit the word “evolution” into everything they publish in order to get the tacit approval of influential senior scientists, who are predominantly atheists, who might not otherwise view the work or the author favorably. Fitting the word evolution into scientific papers is sort of like a salute in the military – an act of obeisance enforced to keep the underlings in line and aware of who’s in charge. -ds

  8. DaveScott, your discussion about reverse engineering of software merits its own thread rather than being lost in this one.

    I very much agree with the “junk DNA ain’t junk” chatter in this thread. Certainly gene regulation is the greater part of what defines a body.

    You are very correct when you suggest that at some point the “tipping point” will be reached for the scientific community in general. This is how it must be. With the way that evolution has weived itself into the social fabric of society, I wonder what sort of upheaval will result.

  9. bfast

    I’ll think about an article comparing and contrasting the study of genomes with reverse engineering of software. Thanks for the suggestion.

    In regard to what’s buried in the genome here’s food for thought – how are instinctive behaviors encoded? Animals have all kinds of complex behaviors that don’t need to be learned. The behaviors are malleable over time and heritable. So those behaviors must be somehow stored in the heritable information inside reproductive cells. The knowledge of how to crow like a rooster and pick up corn with his pecker is contained in every egg destined to hatch into a rooster. No one has a clue yet how this happens. I suggested long ago that means and method of encoding of instinctive behaviors will eventually be discovered in non-coding DNA sequences.

  10. …pick up corn with his pecker…

    I have learned something new today.

    And I am giggling uncontrollably.

  11. Talk about your random mutations.

  12. Dave, not to derail this good thread, but I agree wholeheartedly with your observation at comment #7.
    It’s always been my own private joke to read popular science articles and predict how they will work the word “evolution” in. They usually do, even if they have to tag it in at the end, sort of a “by the way, in case you doubted it, we believe in evolution”.
    It always reads to me like a gratuitous tip of the cap to get an article by the censors.
    But of course, I am not a scientist.

  13. DaveScott,
    I agree with you that instinctive behavior must be passed on in the genes somehow. Certainly animals that have been hatched from eggs, and kept isolated from their kind but which still produce the instinctive behaviors proves that instinct is somehow encoded.

    I have also thought about our distaste for rats. This distaste seems to be particularly strong amongst people of European descent. If I understand my European history correctly, rats used to be beloved animals which people used to be entertained by, and feed. Then came the black plague. Now we seem to have an instinctive distataste for rats. One possibility, of course, is that those who liked rats died, so the “gene” for disliking rats rose to the surface. However, I find that somewhat unlikely. In truth, our distaste for rats seems awfully Lamaracian.

    A quick google browse indicates a belief that there are “instinct genes”, however if genes are defined as portions of DNA which code to proteins, and there’s only about 20,000 of ‘em in me, I doubt if too many are available to code instincts. Further, if the above, then there must also be instinct proteins. Sheut, I should be able to take an instinct pill. I suspect, however, that you are right that instinct is coded into the “non-coding” or “junk” DNA, of course making all of that DNA necessary, rather than junk.

    Alas, more DNA does something, therefore we really are more complex, and our understood complexity is already mind-blowing. Considering that there’s only 600,000,000 years from the development of our phylum until now, RM+NS had better be awfully good at it to get us there.

    If RM+NS is that good at developing complex working systems, someone is going to come up with a good genetic algorithm, and us software developers are going to be out of business.

    It’s kind of hard to imagine instinct being driven by coding genes which is why I like it as an example of what we don’t know about non-coding DNA. Instinct is really just front-loaded knowledge. One might reasonably wonder what the actual and theoretical maximum extents of front-loaded knowledge might be. The way higher animal brains work is they construct a model of reality that’s informed and kept current by the senses. Before the brain sends any conscious action commands to voluntary muscles it runs the action through the model to see what the result is likely to be. Some bits of the model evidently come pre-loaded with important information. Like the mating dance of a bird. Attracting a mate is important, so the model comes preconfigured with information about how to perform the dance and what the likely result will be. Humans don’t seem to have a lot of instinctive behaviors but have more capacity for learned behaviors than any other animal. There’s probably a tradeoff due to storage space limitations in the genome. Space that stores preconfigured model information in other animals in us is used to describe brain anatomy and organization that results in higher capability for abstract thought while making us more vulnerable when young as we have a less functional model of reality at the start. Still we have some important stuff prewired in our model. The suckling instinct is one. A baby knows what that nipple is for, how to find it, and how to operate a symphony of muscles in turning the head, knowing the feeling of finding the nipple, sucking, and swallowing. This simple act requires more in the model than one might think at first blush. It’s little wonder that only 2% of our genome is used for protein coding. How to organize those proteins into a functional animal with a highly organized brain front-loaded with a minimal model of reality and behaviors important to survival… it’s a miracle (if I may use the word without being accused of turning ID into religion) that all this can be accomplished with a genome that’s only a few billion base pairs long. Positing that most of it is wasted space is just plain stoopid. -ds

  14. “One practical benefit is they wouldn’t have to waste time trying to gratuitously fit the word “evolution” into everything they publish in order to get the tacit approval of influential senior scientists, who are predominantly atheists, who might not otherwise view the work or the author favorably.”

    Okay, so they can save some ink. But I’m still not sure that I see how their day-to-day activities would change. Let’s take the article that Dembski referenced as an example (which is not, as the post title suggests, making the claim that natural selection developed Boolean logic).

    Suppose for the moment that the researchers who wrote the article were supporters of ID (I’m presuming they are examples of the ‘genomic luddites’ you mentioned, though I could be wrong). What would they have done differently, if anything, in their research? Would they even have carried out that research? Would they have presented their results differently? You’ve implied that ‘time and chance’ is incapable of explaining the complexity of genetic structure. Okay. Suppose the authors had agreed with that. Would their research program look any different in any significant way, and if so, how?

    I can’t answer this unless you give me a specific example of a research program. -ds

  15. Does taking junk DNA into account drop our similarity to monkeys from 98% to a low-enough level that scientists will soon be able to tell us apart?

    I can’t answer this question unless you give me some specific individuals. For instance, George of the Jungle’s friend A.P.E. will likely never be distinguishable from Professor P.Z. Meyers. We can only ask so much of science then we must take things on faith. -ds

  16. A couple of idle comments:

    First, I believe there are some genes that if knocked out cause changes in what is thought to be instinctual behavior. The example I am thinking of is mounting behavior in mice or rats. I believe there are others so somehow the proteins affect what most would consider some instinctive behaviors.

    Second, I grew to really like rats so I doubt there is any selection going on here but pure socialization. My son brought one home from college and we all were apprehensive about it at first. We went through some typical cliché transitions. First, just pet it; second hold it for a minute; third feed it a grape etc. To make the story short, we became quite fond of the rat and the next Christmas my son gave one to me as a present. They are very smart, have soft fur and if treated well from the beginning they can be friendly pets. We have lots of rat stories but the reason we stopped having one as a pet is they die like clockwork at about 2 years.

    Hamsters are more easily loveable than rats. The long naked tails on the rats I think triggers an instinctual revulsion in people descended from survivors of the Black Death. Hams hardly have any tail at all. Plus they’re just adorable when they stuff their cheeks with so much food it stretches all the way back to the base of their ribs. Unfortunately they don’t live any longer than rats. Instinctual behaviors are undoubtedly easily derailable by protein abnormalities. A deadly abnormality will derail all behaviors! A rat with a malfunctioning sex-related hormone for example would probably not be likely to engage in normal sexual activities. However, that’s akin to saying gasoline controls the behavior of automobile drivers. It does in a way, but not in a nuanced way. All it does is makes driving impossible without it. -ds

  17. Just a wild guess-but some of this “junk DNA” may sit idly by until it’s “time” for another macroevolutionary saltation, and when that moment comes, these codes suddenly come alive and help coordinate a constructive (and, key word, directed) change in the genome, producing a new genus that is viable, structurally sound, and adapted to survive. I like this vague idea better than that of undirected genetic change that can produce nothing. If lowly atoms and molecules are governed by the dizzying complexity of quantum mechanics, then surely genetic change that’s expected to produce any utility must be governed as well by (still largely undiscovered) guiding principles “underlaid” by some form of undefined intelligence.

    Your idea is far less vague than the notion that time and chance sculpted all the life we see. So I wouldn’t hold that against it. See if you can find any evidence that doesn’t fit your wild guess. There’s none that I know of. Evolution appears to be stopped. It may be stopped forever having run its course to completion. The period of great fecundity is certainly over. A distinct new species has not emerged in recorded history and there hasn’t been a new genus in millions of years. Read the papers on the sidebar under John Davison. -ds

  18. Dave,

    We said that the rat had two problems, its “rep” which it obviously deserved and its long tail which as you said tends to repulse at first. I find it hard to believe that the repulsion, which we all had in our family at first, is genetic in the sense that it reflected selection from those who survived the Black Death. That would imply that those who survived were those who kept away from rats instinctively as opposed to those who might have had some anti-body to the disease. I tend to lean to the latter.

    We have repulsive reactions to a lot of animals, snakes, most insects, worms etc. and these may be genetic in some way. But looking at how people’s reaction to the rats changed over time I would think a lot of it is socialization. There is a joke about why lawyers are replacing rats as the animal of choice in lab experiments. One of the answers is that you do not get attached to lawyers.

    Interesting article about the Black Death. Thanks for pointing it out.

  19. What I mean by a ‘research program’, in very general terms, is a set of questions, some possible answers (or hypotheses) to those questions, and methods developed to establish the validity of the answers or test the hypotheses. With respect to the paper referenced by Dembski, the authors outline their program:

    Here, we ask which changes in a CRIF can be caused by a few point mutations in the regulatory region and which changes cannot. This question is related to the way in which the input function can be shaped by evolutionary selection [1]. It is believed that gene networks can “learn” new computations on an evolutionary timescale by means of mutations [22–25]. Changes are mainly due to point mutations, gene duplications, and rearrangements [26–28]. The degree to which mutations can change the computation, without ruining the essential function, may be termed “plasticity” [1,29–32]. The larger the plasticity, the more readily a network can learn new computations in a new environment.

    To address this, we study the plasticity of the lac input function. We measured the effects of point mutations in the lac promoter region on its input function. We find that the lac input function is quite plastic: even a few point mutations can significantly change the CRIF, leading to input functions that resemble pure AND gates, OR gates, and single-input switches. A mathematical model explains these results and lets us predict which types of gates can and cannot be obtained with point mutations.

    So we have the question: which changes in a CRIF can be caused by a few point mutations in the regulatory regions and which changes cannot?

    We have some answers: they show that it takes only a few point mutations to produce diverse CRIF and that these input functions are similar to some Boolean types of logic gates. Their experimental results also suggest that some input functions are not realizable.

    And we have the methods: they outline their experimental methodology and also a mathematical model to predict the kinds of changes possible.

    Now, part of their discussion for why this question would be interesting is related to background assumptions about evolutionary processes. Based on this, I assume that the researchers are at least nominal supporters of modern evolutionary theory.

    So I’ll restate my question: if the authors were supporters of Intelligent Design, what would they have done differently, if anything? Would their questions be different? Their answers? Their methodology? What effect would being an ID supporter have on day-to-day research activity exemplified by this article?

    Thank you providing a specific research program. Nothing at all would change in this. This is experimental biology, they are reverse engineering living tissue. Good stuff. This experimental work is not informed in the least little bit by the notion that RM+NS can change bacteria into baboons in 3 billion years. Thanks for asking. Next! -ds

  20. Okay, here’s ‘next’: What research program would change, and in what way, if the people carrying it out were to adopt ID? Again, I’m referring to the day-to-day activities of the researchers.

    How about if I let Phillip Skell answer your question? Emeritus Professor of Biology John Davison chimes in at the first comment too. Read this. Thanks for asking. -ds

  21. I read what I could of the Skell article (the rest is behind a subscription wall). But the article is irrelevant to my question since I am not claiming that the theory of evolution is in any way necessary or even useful to biological research. However, it does suggest that I reframe the issue slightly:

    1) Is ID in any way necessary to carrying out research in biology?

    2) Even if it is not necessary, does ID provide anything useful to biological research? If so, what?

    A design theoretic view of biological systems should help in targeting research towards fruitful areas and accelerating discovery. Reverse engineering of intelligently designed systems would be the paradigm instead of unraveling the result of random events. Of course we can’t know until there is actually a paradigm change. -ds

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