“The sequence,” whatever you mean by that, is irrelevant in this experiment.
Do you have any idea how clueless your writing is at this point? We are discussing antibodies that bind to antigens, not “sequences that bind to B cells.”
Have you ever considered the idea that your inability to describe things accurately might just reflect a major lack of understanding on your part, or do you just blow through that arrogantly and claim that you understand all this biology better than people who spend their working lives studying it?
The experiment doesn’t bother with FI. It directly and quantitatively measures function F, so we don’t have to argue about your beloved proxy. Isn’t that great, Bill? Doesn’t that get you excited about learning more, instead of flailing around and inventing reasons not to learn?
It has most of the sequence, not functional information. Most of the sequence required is there.
Functional information is an abstraction that relates only to some minimum level of function, the sequence is an actual molecule, and you keep getting the two confused.
In that case, the transition from the system without FI to the system with FI would not at all require the infusion of an amount of information equal to the FI of the working system but only the infusion of the low amount of information that is still missing for performing the function.
Yeah I’m afraid that’s just wrong. The process of recombination or mutation is what creates the FI, and it goes from zero when it is nonfunctional, to however much -log2 of the fraction of functional to nonfunctional sequences is.
To illustrate this point, let’s take the example of cystic fibrosis. Cystic fibrosis is caused by mutations in both copies of the CFTR gene. Imagine that one of the copie of the CFTR gene of a given patient is characterized by a single mutation resulting in say a Phe to Pro transition at position 508 of the protein and that this change in the protein completely abolishes it’s function.
Imagine now that to cure this patient, the physicians decide to correct the mutation, reversing the Pro into a Phe at position 508. Thanks to gene editing technologies, such a thing may not be science fiction anymore.
In the above situation, the FI of the defective protein would be zero, for the protein doesn’t perform its function. But I hope it is clear for everyone here that the defective protein has already almost all the specific bits of information in place for performing the function so that the amount of information that must be infuse by the physicians to cure the patient is only 4,3 bits at most.
It has the sequence, not the functional information. You are again confusing sequence with functional information. I’m sorry but you can’t use FI and not abide by the rules of how the concept is defined, then you’re using some other concept of information. You’re apparently simply using the measure to be -log2 of 20 times sequence length, regardless of whether it is functional or not.
Well then evolution can create arbitrary amounts of information, because it’s just a matter of getting more sequence. Duplicate away.
I see you’re replying. I hope that you can explain your complete lack of interest in an experiment that will directly test your hypothesis, without even getting into FI, because it measures F directly.
Why don’t you want to even think about learning the truth, or at least a far better approximation of it than your empty, ever-changing assertions?
I want to interject here that it is generally not appropriate to publicly question people faith, intelligence, motives, etc. as they are subjective and personal, and frankly it’s just rude.
If someone says something silly, generally it is unnecessary to point out that it is silly. Simply give better information and let the reader see the silliness for themselves.
If someone is ignorant, give them helpful information and offer to help them learn, don’t scold them for their ignorance.
Don’t assume everyone who is on the “other side” is an enemy and that everything they say is a trap or is to score points. Alternatively, be willing to engage with people who believe differently as that is often where both sides will learn something new.
Let’s, again, focus on the science and not get sucked into unhelpful personal attacks and dismissiveness. Passions run high, but cooler heads make a more lasting impact.
In @colewd’s defense George, there is a difference between God having “no interest” and God occasionally doing something miraculous in the history of life. I believe @colewd, in general, has no problem with providence and God working through natural laws. I suspect he just thinks it’s not only providence and natural law that has gotten us to this point.
In response, I will note that Gil’s and Bill’s relentlessly silly evasions have provided nothing but evidence that they lack faith in their assertions. The evidence they have provided is in the form of frantically moving the goalposts, falsely stating their assumptions as facts, and misrepresenting (pretty obviously deliberately) what I have written, all of which are far more rude than anything I am doing.
That doesn’t work.
Multiple studies have shown that simply giving information simply fails to change anyone’s mind about something that is so central to her/his identity; nonintuitively, it makes them dig further into silliness. This is about arrogance and ego, not information. They are literally making up information to justify their fear of looking for correct information!
In my opinion, it is far better to lead someone through the process of checking what they simply think might be true against reality–the scientific method.
Bill and Gil are incredibly ignorant about the subjects on which they pontificate. I am offering to help them learn and they are avoiding learning. That is obvious, even to you.
I agree that we should focus on the science. That means empirically testing hypotheses. Gil and Bill are doing anything but science.
I would say that the function of VDJ recombination is to produce a repertoire of antibodies with enough diversity so that the immune system can mount a B cell response against nearly any possible foreign antigen it may encounter. Now, if you experimentally delete several V or D or J segment of a hematopoietic stem cell, you will reduce the diversity of the antibody repertoire, hence reduce the ability of the IS to recognize a large diversity of antigens. And the more segments you will delete, the more you will make the immune system sluggish. This I think demonstrates that a large part of the functional information present within the naive B cell compartiment preexists in the stem cells.
Gil, let’s go through this and get more specific and quantitative.
That’s only part of the picture, as I hypothesize that somatic hypermutation is far more functionally important than you want it to be.
Let’s test that hypothesis and yours at the same time. Let’s specify a very relevant antigenic challenge: a real viral infection. Do you agree that it is an appropriate test of function?
Good so far, but “several” is disappointingly, but predictably, vague.
How many? There is the heavy chain array and two light chain arrays: lambda and kappa.
What does your hypothesis predict if we completely inactivate the kappa light-chain array so that no kappa light chains can be made?
No, Gil. YOUR HYPOTHESIS PREDICTS a reduced diversity of the antibody repertoire. Please try to be just a bit more modest and state hypotheses as hypotheses, not as facts.
Science requires the humility to consider the question, “What will I observe if I’m wrong?” Do you have enough humility to do that?
Yes. That’s another prediction of the hypothesis.
You’re being way too fuzzy here. How many segments and how sluggish? We know the numbers of segments and we can quantitate the antibody response, so those adjectives are unnecessary.
It would demonstrate that if it was true, but all you’ve offered is assertions and fuzzy adjectives. Can you try to be a bit more humble and refrain from falsely presenting your hypotheses as facts?
Let’s test it together, clearly stating hypotheses as hypotheses, predictions as predictions, and using actual numbers, not vague adjectives, n’est-ce pas?
I believe that hypermutation works as a mechanism of the immune system. The experiment is nice but it will have little impact either way as far as showing that FI can be created de novo by cellular mechanisms. If this is not your claim as you intimated earlier we have common ground.
I think you should stop using the term functional information(FI) incorrectly, and just stick with “sequence-information” or something like that, and define it (as you appear to do) merely as -log2 of alphabet size multiplied by sequence length. Since apparently the function of the sequence is irrelevant to whether you think it has information.
It really makes it very difficult to communicate meaningfully here if you insist on using different terms interchangeably. It is potentially very misleading, since depending on how you define and use the concepts, they can have radically different implications.
Please try to be consistent, and stick with a single definition and make it clear when you’re using just “information” or “sequence-information”, that this is NOT EQUIVALENT to Functional Information(FI) as defined by Hazen et al 2007.
I fully support this proposal for a test. It would be able to tell us if the function can only be found because the information is “mostly”/“largely” already present. Surely if we delete “most” of that information, finding a successful immunoglobulin molecule would be practically hopeless?
Of course, it would be really helpful if Gil would more accurately define just what his vague references to “most” or “largely” is.
@gbrooks9, well, I don’t want to speak for @colewd, he can answer himself. However, I think I can offer some possibilities for Christians who are attracted to YEC/OEC/ID.
I think for many Christians there is a sense that when God reveals himself supernaturally he vindicates their belief and faith. I think for many (maybe most), the idea of God working through the ordinary means of evolution is a bit of an anti-climatic let down compared to the undeniable power of God literally speaking the universe and life into existence in the (relative) blink of an eye. Scientific, objective, proof of that radically unnatural beginning to the universe would vindicate the Christian and call the atheist to account for rejecting the obvious evidence for God’s existence and power.
I think for many Christians the grounding of their faith is primarily in the Bible, and therefore things like matching biblical texts with modern science and archeology are so vital as it provides evidence for inerrancy and divine authorship. For many of these Christians, objective evidence for inerrancy proves divine authorship which in turn proves Jesus was raised from the dead. If Genesis is not true (plain reading backed up by scientific findings) then why should we believe all that Jesus stuff? An origin story that is scientifically indistinguishable from the one the atheists tell would be unthinkable. Ironically, science is critical for these folks because they are using it to defend special revelation.
I think for many Christians, the idea of universal common descent is a bit weird and unpleasant. As one person in my summer book club put it, “people and Neanderthals I get, but people being related to lizards, that’s just weird”. I think it’s tough for people to balance being a part of nature and yet so obviously different. The fact that we distinguish between “natural” and “human-derived” (climate change, food, medicine, etc.) gives an idea of this innate feeling that we are somehow different. For the Christian a logical conclusion is that somehow we were made different. God using ordinary means, especially evolution, seems counter to that intuition. Think about how much harder it is to figure out the nature of the Imago Dei when there is no clear line in the sand between our origins and that of a pet or farm animal. For a long time the Image of God was naturally equated with those properties that separated mankind from the animals.
It is exactly what I said for I explicitly recognized that a system (or a sequence) unable to perform the function has zero FI.
If most of the sequence required is there, it means that it has almost all the necessary bits of information to implement the function.
I really don’t understand your feud here. @gpuccio has learned us that « FI is a property of the function, the minimal number of specific bits necessary to implement the function ». A given sequence of aa can or cannot implement the function. If it can, it means that it has all the specific bits necessary to perform the function. If it can’t, it means that one or more bits is missing. In my example of the CFTR mutant, the right aa is missing at position 508, meaning that the mutant CFTR lack 4,3 bits to perform the function.
You’re wrong here. To see this, please consider my example of the mutant CFTR gene. Would you say that by reversing the Pro into a Phe at position 508 the physicians would have generate an amount of information equal to the FI of the functional CFTR?
Function is a possible attribute of a sequence. Indeed and again, a sequence can implement a function or not. If it can, then it has all the FI, ie, all the specific bits necessary to implement the function.
You are building a straw man for I have never equated FI with sequence information in the sense you are using it here. Sorry to tell you that, but I am starting to wonder whether you are arguing in good faith on these matters. Hope I’m wrong.
Which means that FI can arise almost all at once from the final changes in a process of blind, random “searches” thru sequence space. That appears to be the opposite of what you are claiming.
