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Author Topic:   Manipulation of DNA by cells?
Taq
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Message 13 of 36 (668780)
07-24-2012 12:27 PM
Reply to: Message 11 by greentwiga
07-23-2012 6:20 PM


Though there are about 2% genetic differences between humans and Chimps, there are many unstated differences in timing.
Those differences in gene regulation are due to differences in DNA sequence. One is strongly related to the other.
Also, humans do not give birth to chimpanzees. Obviously, this is not about the human genome being plastic enough to produce a wide array of variation. So we can not explain the differences between species solely on epigenetic factors. The differences are due to sequence differences that manifest themselves as differences in gene regulation.

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Taq
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Posts: 9972
Joined: 03-06-2009
Member Rating: 5.5


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.
Just a moment...
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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Taq
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Posts: 9972
Joined: 03-06-2009
Member Rating: 5.5


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
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Posts: 9972
Joined: 03-06-2009
Member Rating: 5.5


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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Taq
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Posts: 9972
Joined: 03-06-2009
Member Rating: 5.5


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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Taq
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Posts: 9972
Joined: 03-06-2009
Member Rating: 5.5


(1)
Message 31 of 36 (671027)
08-21-2012 5:18 PM
Reply to: Message 30 by zi ko
08-21-2012 3:52 PM


Re: Meaningless controversy
Fortunatly during last years it became more than evident, that environment forwards to genome information that plays substantial role in life evolution.
Not at all. Ever since we first discovered the molecular mechanisms involved with DNA (early 1960's?) we have understood that the gene pool of a population changes through time due to the transfer of information produced by selection. It is selection that produces the information we see in genomes today.
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?
Evolution? Absolutely yes. The information in genomes is a direct record of past evolutionary events.
Origin of life? Very difficult to say. I think only the broadest strokes can be pulled from modern genomes. For example, we can see a central role for RNA in modern life. It acts in many different roles, from gene regulator to producer of proteins to enzyme. I think this is strong evidence that RNA was the primary player in the first life. RNA can act in all of the roles that are necessary for life, from inheritance to enzymatic reactions.
Edited by Taq, : No reason given.

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 Message 34 by herebedragons, posted 08-22-2012 10:33 AM Taq has replied

  
Taq
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Posts: 9972
Joined: 03-06-2009
Member Rating: 5.5


(1)
Message 33 of 36 (671099)
08-22-2012 10:18 AM
Reply to: Message 32 by zi ko
08-22-2012 9:35 AM


Re: Meaningless controversy
Very intersting. Could RNA role be thought as something like epigenetics, though far more reaching, extented an deeper mechanism?
I don't think so. RNA is short lived in the cell and are regularly degraded through different mechanisms. I really don't see a role for different RNA's in inheritance. In the short term, RNA could definitely regulate gene expression. However, DNA is still the molecule responsible for inheritance in modern organisms. You need to change the DNA sequence to get meaningful evolutionary change.
Edited by Taq, : No reason given.

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Taq
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Posts: 9972
Joined: 03-06-2009
Member Rating: 5.5


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Message 35 of 36 (671111)
08-22-2012 10:56 AM
Reply to: Message 34 by herebedragons
08-22-2012 10:33 AM


Re: RNA world hypothesis
RNA is much less stable than DNA and is prone to hydrolysis. Stable, functional RNA units are usually associated with proteins and involve complex folding patterns as contrasted to DNA structures. Use of RNA as the main storage unit would not be impossible but rather energy intensive, not particularly conducive to early life with lower energy resources (assuming photosynthesis, mitochondria, electron transport and such were not in existence yet)
It is also worth mentioning that RNA's instability in the modern cell is due to RNA degrading enzymes. Given the right environment, RNA can be relatively stable. A reducing environment would obviously be best, and that is what we have in the early Earth. I fully agree that DNA is more stable than RNA.
RNA is not known to self replicate in nature (at least as far as I know) and is instead transcribed from DNA.
That depends on how you look at it. There is not a strict hierarchy in the cell. Does DNA make DNA? No. Proteins make DNA in combination with RNA primers, and it is ribosomal RNA's and tRNA's that make proteins from mRNA's. DNA could be looked at as just a more stable form of RNA that is stored for future use.
As far as the role RNA plays in modern organisms ... without DNA regulation of these processes it is only speculation of what RNA's role would be in early life. It shows that RNA can perform these functions and certainly does play a central role in modern life, but it is unclear that RNA could perform these functions without DNA regulation.
It is RNA and proteins made by RNA that controls gene expression. I would also suspect that RNA's can interact and control their own activity just as proteins can.
Of course, I am make very strong statements here that do breakdown a bit when scrutinize, but I do think that the major themes are there. RNA still plays a central role in the cell. It could be argued that we still live in an RNA World.

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