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Author Topic:   Manipulation of DNA by cells?
Dr Jack
Member (Idle past 147 days)
Posts: 3507
From: Leicester, England
Joined: 07-14-2003


Message 16 of 36 (669455)
07-30-2012 6:57 AM
Reply to: Message 15 by shadow71
07-29-2012 9:05 PM


Do these processes, that deliberately alter the structure of the genome, indicate in some way a purposeful process?

What do you mean by a purposeful process?

It isn't just something that happens, it's a vital part of how the immune system functions. The random recombination produces a "library" of antibodies that will bind to almost any pathogen.


This message is a reply to:
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Replies to this message:
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Taq
Member
Posts: 7670
Joined: 03-06-2009
Member Rating: 4.5


Message 17 of 36 (669489)
07-30-2012 12:58 PM
Reply to: Message 15 by shadow71
07-29-2012 9:05 PM


Do these processes, that deliberately alter the structure of the genome, indicate in some way a purposeful process?

I think it could be said that the ability to produce random mutations is an evolved function in all species. For example, the binding site of polymerases are looser than they need to be. This results in a random mutations.

quote:
We describe the use of a series of gradually expanded thymine nucleobase analogs in probing steric effects in DNA polymerase efficiency and fidelity. In these nonpolar compounds, the base size was increased incrementally over a 1.0- range by use of variably sized atoms (H, F, Cl, Br, and I) to replace the oxygen molecules of thymine. Kinetics studies with DNA Pol I (Klenow fragment, exonuclease-deficient) in vitro showed that replication efficiency opposite adenine increased through the series, reaching a peak at the chlorinated compound. Efficiency then dropped markedly as a steric tightness limit was apparently reached. Importantly, fidelity also followed this trend, with the fidelity maximum at dichlorotoluene, the largest compound that fits without apparent repulsion. The fidelity at this point approached that of wild-type thymine. Surprisingly, the maximum fidelity and efficiency was found at a base pair size significantly larger than the natural size. Parallel bypass and mutagenesis experiments were then carried out in vivo with a bacterial assay for replication. The cellular results were virtually the same as those seen in solution. The results provide direct evidence for the importance of a tight steric fit on DNA replication fidelity. In addition, the results suggest that even high-fidelity replicative enzymes have more steric room than necessary, possibly to allow for an evolutionarily advantageous mutation rate.
http://www.pnas.org/content/102/44/15803.long

With antibody production, we see the same thing. The random admixture between different gene sets to produce a single antibody results in a vast library of bindings sites. This is an advantageous system, so it is selected for.


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shadow71
Member (Idle past 976 days)
Posts: 706
From: Joliet, il, USA
Joined: 08-31-2010


Message 18 of 36 (669596)
07-31-2012 11:25 AM
Reply to: Message 16 by Dr Jack
07-30-2012 6:57 AM


Mr Jack writes:

It isn't just something that happens, it's a vital part of how the immune system functions. The random recombination produces a "library" of antibodies that will bind to almost any pathogen.

My question is are these "library" of antibodies binding to a pathogen in a random manner or some type of directed manner?


This message is a reply to:
 Message 16 by Dr Jack, posted 07-30-2012 6:57 AM Dr Jack has responded

Replies to this message:
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shadow71
Member (Idle past 976 days)
Posts: 706
From: Joliet, il, USA
Joined: 08-31-2010


Message 19 of 36 (669597)
07-31-2012 11:28 AM
Reply to: Message 17 by Taq
07-30-2012 12:58 PM


Taq writes:

With antibody production, we see the same thing. The random admixture between different gene sets to produce a single antibody results in a vast library of bindings sites. This is an advantageous system, so it is selected for.

When you say "selected for" are you saying these are directed functions for fitness?
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Taq
Member
Posts: 7670
Joined: 03-06-2009
Member Rating: 4.5


Message 20 of 36 (669606)
07-31-2012 12:24 PM
Reply to: Message 19 by shadow71
07-31-2012 11:28 AM


When you say "selected for" are you saying these are directed functions for fitness?

No, I am not. What I am saying is that individuals with mutations that increase polymerase fidelity are not as fit as those with polymerases with less fidelity. This is not directed function. This is evolved function.


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Taq
Member
Posts: 7670
Joined: 03-06-2009
Member Rating: 4.5


Message 21 of 36 (669607)
07-31-2012 12:32 PM
Reply to: Message 18 by shadow71
07-31-2012 11:25 AM


My question is are these "library" of antibodies binding to a pathogen in a random manner or some type of directed manner?

Binding is a physical process. It is no more directed than hydrogen is directed to bind to oxygen.

This system also follows evolutionary principles. First, you should read up on V(D)J recombination:

http://en.wikipedia.org/wiki/V(D)J_recombination

This is how the B-cell library is formed. Each B-cell clone expresses a different antibody that was formed from a random shuffle of the V, D, and J components. If one of these antibodies binds to a pathogen then the B-cell is turned on. It will start to divide into more cells and pump out massive amounts of that antibody. So what we have is a random step followed by a selection step, just like evolution.

What does NOT happen is a directed process. The B-cell does not find an antigen and then specifically combine the V, D, and J segments so that they will produce an antibody able to bind the antigen. Instead, the mature B-cell has the only antibody it will ever express before exposure to the antigen.

Edited by Taq, : No reason given.


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Dr Jack
Member (Idle past 147 days)
Posts: 3507
From: Leicester, England
Joined: 07-14-2003


Message 22 of 36 (669686)
08-01-2012 2:07 PM
Reply to: Message 18 by shadow71
07-31-2012 11:25 AM


My question is are these "library" of antibodies binding to a pathogen in a random manner or some type of directed manner?

A random manner; that's the brilliance of the system. If it worked in a fixed manner it would only work against pathogens previously encountered at sufficient levels to drive evolution of immune responses to them. By randomly recombining elements it covers a much greater epitope space.


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shadow71
Member (Idle past 976 days)
Posts: 706
From: Joliet, il, USA
Joined: 08-31-2010


Message 23 of 36 (669689)
08-01-2012 2:25 PM
Reply to: Message 21 by Taq
07-31-2012 12:32 PM


From the wiki segement writes:

(D)J recombination, also known as somatic recombination, is a mechanism of genetic recombination in the early stages of immunoglobulin (Ig) and T cell receptors (TCR) production of the immune system. V(D)J recombination takes place in the primary lymphoid tissue (the bone marrow for B cells, and Thymus for T cells).V(D)J recombination nearly randomly combines Variable, Diverse, and Joining gene segments of vertebrates, and because of its randomness in choosing different genes, is able to diversely encode proteins to match antigens from bacteria, viruses, parasites, dysfunctional cells such as tumor cells,[1] and pollens.

Shapiro in his book "Evolution: a view from the 21st century", defines natural genetic engineering as follows:

"The collective set of biochemical capabilities that cells have to restructure their genomes by cleaving, splicing, and synthesizing DNA chains. much as we do in modern biotechnology."

It seems to me that they are both describing the same process.

I am very much amazed that even though the process is said to be random, it appears that it is in fact a process that places the necessary genes where they are needed. Am I way off base on this?

The wiki artice says "nearly randomly combines..."
Why the "nearly" observation? Is it more than random?


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Dr Jack
Member (Idle past 147 days)
Posts: 3507
From: Leicester, England
Joined: 07-14-2003


(2)
Message 24 of 36 (669742)
08-02-2012 6:27 AM
Reply to: Message 23 by shadow71
08-01-2012 2:25 PM


I am very much amazed that even though the process is said to be random, it appears that it is in fact a process that places the necessary genes where they are needed. Am I way off base on this?

Say I want to generate a random registration number. It consists of two letter, the numbers 0, 1, 5 or 6, another number 0-9, and a sequence of three letters.

I get my bag of scrabble tiles out for the letters, and pull out two. Then I take some Rummikub tiles pick out just the numbers 1, 5, 6 and 10 (counting 10 at 0), put them in a bag and pick one out a random. Next, I pop the numbers 1-10 in and pick out another, finally I pick three more scrabble tiles out.

Wow: BH07 LUA - I've just generated a numberplate at random, but all the letters and numbers are in the right order and its a perfectly correct and valid numberplate.

Things can be random while still being structured. Random does not mean anything goes.


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Replies to this message:
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shadow71
Member (Idle past 976 days)
Posts: 706
From: Joliet, il, USA
Joined: 08-31-2010


Message 25 of 36 (669778)
08-02-2012 4:15 PM
Reply to: Message 24 by Dr Jack
08-02-2012 6:27 AM


Mr Jack writes:

Wow: BH07 LUA - I've just generated a numberplate at random, but all the letters and numbers are in the right order and its a perfectly correct and valid numberplate.

Is your numberplate going to give you access to the computer site that requires a password?

It seems the random genes will give the needed access.


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 Message 24 by Dr Jack, posted 08-02-2012 6:27 AM Dr Jack has responded

Replies to this message:
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Dr Jack
Member (Idle past 147 days)
Posts: 3507
From: Leicester, England
Joined: 07-14-2003


Message 26 of 36 (669782)
08-02-2012 5:26 PM
Reply to: Message 25 by shadow71
08-02-2012 4:15 PM


If I make enough of them, yes, it will. And this is, essentially, the principal behind the immune system. Random recombination produces vast numbers of different antibodies, so that when a novel pathogen enters the body chances are that one of the vast number of random antibodies will recognise the pathogen. The body then identifies this fact and mass produces the antibody.
This message is a reply to:
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Replies to this message:
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shadow71
Member (Idle past 976 days)
Posts: 706
From: Joliet, il, USA
Joined: 08-31-2010


Message 27 of 36 (669813)
08-03-2012 8:30 AM
Reply to: Message 26 by Dr Jack
08-02-2012 5:26 PM


Mr Jack writes:

Random recombination produces vast numbers of different antibodies, so that when a novel pathogen enters the body chances are that one of the vast number of random antibodies will recognise the pathogen. The body then identifies this fact and mass produces the antibody.

When you say "chances are..." is that a random chance or is the body in some way "programmed" to recognise the pathogen?

Programmed may be a bad choice of words, but it is the best I can come up with at this time.

Also how does the body then produce the necessary antibody? It would seem that this could not be random, but "programmed" in some way.

I am not trying to be difficult. I think you may know my philsophy, that of "Creation Continium" per the Roman Catholic church, and that there is in fact a cause for all these wonderous events.


This message is a reply to:
 Message 26 by Dr Jack, posted 08-02-2012 5:26 PM Dr Jack has responded

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Dr Jack
Member (Idle past 147 days)
Posts: 3507
From: Leicester, England
Joined: 07-14-2003


Message 28 of 36 (669840)
08-03-2012 5:36 PM
Reply to: Message 27 by shadow71
08-03-2012 8:30 AM


The body's immune system doesn't carry any specific defences against any pathogen by default. It simply produces a sufficient range of antibodies to detect almost anything. Antibodies can be raised to recognise almost any protein (actually a small part of it) based on random recombination of a small number of pieces.

I'm afraid I can't remember off-hand how the body identifies and clones the antibodies needed in response to an attack. Hopefully another poster can fill you in.


This message is a reply to:
 Message 27 by shadow71, posted 08-03-2012 8:30 AM shadow71 has not yet responded

  
Taq
Member
Posts: 7670
Joined: 03-06-2009
Member Rating: 4.5


Message 29 of 36 (669979)
08-07-2012 11:48 AM
Reply to: Message 27 by shadow71
08-03-2012 8:30 AM


When you say "chances are..." is that a random chance or is the body in some way "programmed" to recognise the pathogen?

Chances are that one of the randomly arranged antibodies will bind to a portion of the pathogen allowing the immune system to recognize it as a foreign body.

Also how does the body then produce the necessary antibody? It would seem that this could not be random, but "programmed" in some way.

Selection would be a better description. The library of antibodies are expressed on the surface of B-cells with each B-cell producing one random arrangement of the V(D)J genes. If something binds to that antibody then that B-cell is "turned on". It will start to rapidly divide to produce more B-cells like itself and pump out massive amounts of the antibody into the bloodstream. There are also different types of antibodies (IgM, IgG, IgA) that are expressed at different times and in different parts of the body. IgM usually comes up first while IgG comes up later and offers long term immunity.


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zi ko
Member (Idle past 1662 days)
Posts: 578
Joined: 01-18-2011


Message 30 of 36 (671019)
08-21-2012 3:52 PM


Meaningless controversy
It is strange.For very long time the two different shools of thought (evolutionists and creationists) are fighting each other,in the wrong field, where no logical verdict can be drown.The only result is just tension between them.
Fortunatly during last years it became more than evident, that environment forwards to genome information that plays substantial role in life evolution. We see this role to increase each day thanks to cellular biology research.
This fact does not negate evolution theory, or its basic ideas ( e.g random mutations, n. selection), but surely decreases its size of participation in creating life divergence. Nature is quite clever not to use any possible useful mechanism for life preservation and advance of evolution. And information flow together with random mutations and n. selection are so useful things no to be used.
The real and critical question lies here: is this information, arriving from natural laws, able to give the answers needed to explain life appearance and then life evolution? Or something more is needed?

Edited by zi ko, : No reason given.


'If that much-spoken 'evidence" of followers of random mutations is this 'some evidence' of Panda, then there is a serious matter of credibility in this forum.

Replies to this message:
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