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Member (Idle past 5618 days) Posts: 239 From: Upper Portion, Left Coast, United States Joined: |
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Author | Topic: Problems with Chromosomal Evolution - From Circular to Linear | |||||||||||||||||||||||||||||||||
jt Member (Idle past 5618 days) Posts: 239 From: Upper Portion, Left Coast, United States Joined: |
Several people have asked me to start a thread about problems for the theory of evolution in the area of genetics. At the risk of biting off more than I can chew, here goes...
There is a large gap between the chromosomal structures of prokaryotes (cells without nuclei) and eukaryotes (cells with nuclei) that I maintain cannot be bridged by the theory of evolution. There are many huge differences in transcription, storage, etc., but for the sake of a narrow topic (and because I know little about those other things) I will restrict this topic to one of the simplest differences, the shape. A prokaryotic chromosome consists of a circular strand of DNA, while a eukaryotic chromosome is a linear strand of DNA. The actual shape isn’t very important, but what it entails is. (note: If you know what a telomere is, what telomerase does, and the function of a telomere cap, you can skip the next 7 paragraphs) Every time a linear chromosome is replicated, some of the DNA on each end is destroyed. Without some form of protection, a linear chromosome deteriorates rapidly and quickly becomes useless. When that happens, the cell is unable to repair itself and soon dies. Linear chromosomes do exist, though, and have protection in the form of telomeres. A telomere is a section of DNA at the end of a linear chromosome made up of a large number of repeats of a small sequence of base pairs (for example, in humans the sequence is TTAGGG). This DNA acts as a sort of buffer zone for the rest of the chromosome; it is destroyed in place of vital segments. If the protection system were that simple, the line of cells would last a little longer, but not by much. If the telomeres are being destroyed from both ends, it is only a matter of time before they are completely used up and the rest of the chromosome starts being destroyed. This problem is solved in the form of an enzyme, telomerase, which lengthens telomeres once they have deteriorated. Telomerase is a complex protein (complex protein is redundant, because all proteins are complex, but it sounds better than just saying protein) made up of several subunits with different purposes. There is a RNA-transcriptase subunit which copies the telomere sequence, and there is at least on other subunit that is attracted to/identifies the protein caps of telomeres. Telomerase needs regulation, though. If it was left on its own, it would continually add useless DNA as fast as it could, using up a vast amount of nucleic acids, burdening the cell’s production. Also, all of the huge amount of DNA would be copied to all daughter cells, which would then add to it and have to copy it to their daughters, etc. Fairly rapidly the cells would be unable to support themselves. Protein caps are the last part of the protective system. At the very end of the chromosome, at the end of the telomere segment, is a protein (Pot1) that serves two purposes. First, to provide a substance telomerase can identify; second, to provide protection to the telomere tip. Experiments have shown that cells cannot survive without this additional protection, the chromosome rapidly deteriorates. This cap is removed during replication of the chromosome, and then put back once replication is complete. The attraction function of the cap is also vital. Without something for telomerase to identify, it would be unable to find the end of the chromosome to repair it. The chromosome would be protected from normal wear and tear, but would still be eventually destroyed by replication. IF YOU SKIPPED READING ABOVE, START AGAIN HERE To go from circular DNA to linear DNA is not something that could take more than a single generation to happen — if it didn’t happen all at once, the cell would die, and there would be no further generations. Here is a list of the minimum required to go from circular to linear chromosomal structure: 1. The creation of telomerase, a complex protein2. The creation of a protein that binds to the ends of telomeres 3. Regulatory mechanisms for telomerase 4. Modification of the DNA replication system to enable it to remove/replace telomere endcaps The creation of at least two proteins, the creation of a regulatory system, and the suitable modification of the DNA replication system by a single set of mutations is highly incredible. The chances of mutations occurring such that those would all work is nearly impossible. That is not all, though. Say that all those mutations did take place, and the DNA was such that the next daughter cell would have functional, stable linear chromosomes. That would take thousands of mutations concentrated in only a few genes. That is far, far beyond what is even remotely normal for rates of mutation. That extremely high rate of mutations can only be explained one of two ways: either the DNA copying mechanism broke and went berserk (to use scientific terminology), or there was an extremely powerful mutagen present. In both cases, the mutations would not be restricted to the genes in question, but would affect the replication of the entire chromosome. There is no way the daughter cell could survive with DNA corrupted that badly. But even, miraculously, if the daughter cell did survive, it would not long be able to survive the mutagen or berserk DNA synthases. Well, say all of that did occur. Circular chromosomes are much more stable than linear chromosomes. What would have caused natural selection to favor the new mutant, and cause it to evolve into all higher forms of life (all multicellular organisms have linear chromosomes), while keeping the safer, circular DNA confined to single celled organisms? And if that much change can happen in a single generation, why do yeast and humans (both eukaryotes, but far apart on the evolutionary ladder) use the exact same proteins to maintain their chromosomes? (Did evolution just stop?) Why do the even have similar chromosomal structures? [edited in: after posting this I learned that telomerase is the name for a family of proteins, not a specific protein. I am thus retracting the three previous questions from debate] Awaiting replies,JT This message has been edited by JT, 08-20-2004 03:29 PM This message has been edited by JT, 08-22-2004 08:26 PM This message has been edited by JT, 08-23-2004 11:49 AM
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AdminNosy Administrator Posts: 4754 From: Vancouver, BC, Canada Joined: |
Thread moved here from the Proposed New Topics forum.
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Loudmouth Inactive Member |
JT,
Just a couple points. Firstly, if the telomerase existed before linear DNA, then the bridge is easily constructed. This would allow unlimited cell division. In mutlicellular systems, the telomerase is turned off in order to stop cancerous growth, so actually it would make sense if the telomerase was around before linear DNA. The origin of the telomerase could have been a DNA polymerase or a mutated DNA repair mechanism originally used to fill in gaps within circular DNA. It wouldn't be that difficult for the telomerase to move from filling in gaps to DNA elongation. Next, it is very possible that protein caps were not necessary in a simpler linear DNA system. This seems to be a redundant system, which is what we see a lot within evolved systems. That is, a simple system will work for a simple organism, but once you are regulating tissue production and other more complex developmental pathways it becomes necessary to have more complex on/off systems. Also, a protein signalling cascade could have also evolved to magnify certain signals, such as is seen in the evolution of the blood clotting cascade. The mistake I see in your reasoning is assuming that the nuclear systems we see today came about in one fell swoop. This is not the case, as can be seen in structures that actually fossilize. For instance, the development of tetrapody (walking on land) can be observed in the fossil record and what we see is that the first land walkers were pretty clumsy and the limb system was pretty simple. However, later on in the fossil record (eg mammals) the development of land walking is quite complex and fine tuned. We would expect the same thing with cell biology, small changes that result in very complex and fine tuned systems over time. Therefore, it is your challenge to prove that a simpler system for linear DNA has never existed. I know this is impossible to do, but it is your argument that no such system ever existed.
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pink sasquatch Member (Idle past 6045 days) Posts: 1567 Joined: |
Hey JT-
Nice opening post, and definitely a point of worthy discussion I haven't seen mentioned in the forum before. One thing you have to consider when you think about the evolution of a biological process or structure, (in this case linear chromosomes), is the simplest form of that process, and not the process as it exists in a mammalian cell. In this case, linear chromosomes exist in some viruses and bacteria, without the complex telomere maintenance you describe above. In some cases, repeated and palindromic sequences at the end of these chromosomes fold into complex hairpin loop structures (they fold back on themselves and bind complementary sequence) to protect free strand ends. (Searching for "linear bacterial chromosome" at http://www.pubmed.org should give you lots of interesting abstracts to look at).
Thus it appears that the sequence itself is sufficient to protect the end of a linear chromosome in some situations, without any protein involvement. In certain bacteria, the chromosomes are unstable/reversible, in that they commonly go from circular to linear and back again.(reference) While such instability is negative in one sense, it also serves as a mechanism to "accelerate" evolution, since it provides more opportunities for rearrangements and duplications. Also, the fact that many simple linear chromosomes use palindromic hairpin loops as simple telomeres supports a plausible course of evolution for the linear chromosome. The palindromic sequence could have arisen within the stability of the circular chromosome (perhaps from a small duplication event), allowing for potential hairpin loops to form. Subsequent breakage of the circular chromosome near such loops would result in a linear chromosome having a "telomere" before it was even linear... There are still many points that deserve to be discussed from your opening post, but complex telomere maintenance does not appear to be required for linear chromosomes.
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jt Member (Idle past 5618 days) Posts: 239 From: Upper Portion, Left Coast, United States Joined: |
In mutlicellular systems, the telomerase is turned off in order to stop cancerous growth, so actually it would make sense if the telomerase was around before linear DNA. Circular chromosomes have no ends which need to be protected, so do not need telomeres, and thus do not need telomerase.
The origin of the telomerase could have been a DNA polymerase or a mutated DNA repair mechanism originally used to fill in gaps within circular DNA. I think what you mean is DNA polymerase 1 (if not, please correct me). DNA polymerase 1 removes RNA primers during replication, leaving a gap in one of the strings composing the double helix. It then uses its capabilities as a polymerase to fill the gap, using the pattern the DNA strand gives it. The only overlap between these two enzymes are the polymerase subunits, which are substantially different. Telomerase creates DNA following an RNA pattern embedded in its reverse transcriptase protein, while DNA polymerase 1 creates DNA following an external DNA pattern. In addition, telomerase has at least two more, highly specialized protein subunits aside of its polymerase subunit. These subunits have very little to no overlap. (note: in my opening post, I referred to the enzyme telomerase as a "protein," but it is actually composed of several proteins and an RNA segment) Also, nearly everywhere I have found a detailed description of telomerase, its polymerase protein (which is the only protein in the enzyme which could have much overlap with DNA polymerase 1) is described with words such as "novel" and "unusual." If it was even slightly similar to DNA synthase 1 that would be common knowledge, and if it was even remotely similar to other synthases it would not be called "unusual."
Next, it is very possible that protein caps were not necessary in a simpler linear DNA system. Pink Sasquatch went into more detail on this, and I am researching that and will reply to his formulationof this argument in my response to his post.
The mistake I see in your reasoning is assuming that the nuclear systems we see today came about in one fell swoop. It is my contention that in the case of this system, it would have had to come about in one fell swoop.
Therefore, it is your challenge to prove that a simpler system for linear DNA has never existed. Hairpin telomeres might be the simiplest system possible, or at least the simplest system known. I am researching those in response to Pink Sasquatch's post. I cannot prove that a simpler system has never existed, but I think it would be possible to show that the existence of a simpler system is improbable or unknown today. Pink Sasquatch, I am researching in order to respond to your post, but it will be at least tommorrow (probably) before I reply to it.
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lfen Member (Idle past 4699 days) Posts: 2189 From: Oregon Joined: |
JT
Just wanted to say that this is a very well done topic. I'm very impressed. I quite expect I'll learn a lot following this. I doubt I'll have anything to offer. lfen
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RAZD Member (Idle past 1427 days) Posts: 20714 From: the other end of the sidewalk Joined: |
Nice topic. The only comments I have to add are:
(1) That breaks in the circular chromosome would occur leading to repeated attempts at linear chromosome arrangements. These could just keep happening until a process co-evolves that allows it to survive. (2) It could be argued that the original replication system would have used a linear system (see discussion of RNA replication), and thus have developed a primitive solution to the end problem before finding the more stable circular system, and that this would have continued to be available when such breaks occured as in (1) above. Remember that you are dealing with differential survival rates and those that do it better faster have more replicating survivors. I look forward to the next post Thanks. This message has been edited by RAZD, 08-21-2004 12:10 AM we are limited in our ability to understand by our ability to understand RebelAAmerican.Zen[Deist
{{{Buddha walks off laughing with joy}}}
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jt Member (Idle past 5618 days) Posts: 239 From: Upper Portion, Left Coast, United States Joined: |
Nice opening post Thanks.
Thus it appears that the sequence itself is sufficient to protect the end of a linear chromosome in some situations, without any protein involvement. From http://www.ym.edu.tw/ig/cwc/end_troubles/End_Troubles.htm:
quote: Hairpin telomeres cannot be replicated with normal DNA synthases, they need a special enzyme, telomere resolvase (source), to replicate and appropriately fold them. This enzyme is very picky - it only works on certain palindromic sequences:
quote: For a circular chromosome to become linear and use hairpin telomeres, it would not only need telomere resolvase, but a terminal palindromic sequence which exactly matched the size and pattern of that for which the enzyme was coded. It is extremely implausible that something like that could happen in one generation.
In certain bacteria, the chromosomes are unstable/reversible, in that they commonly go from circular to linear and back again. Streptomyces (with linear chromosomes) have two types of telomeres - one has a protein cap, the other is a hairpin. They thus need telomerase and telomere resolvase. When they become circular, they retain those enzymes, and the regulatory systems for them. Returning to a linear state doesn't need anything new, it is simply a different shape. RAZD - I'm working on your post, I'll get my reply to you probably tommorrow. This message has been edited by JT, 08-22-2004 07:57 PM
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jt Member (Idle past 5618 days) Posts: 239 From: Upper Portion, Left Coast, United States Joined: |
In the opening post, I said:
And if that much change can happen in a single generation, why do yeast and humans (both eukaryotes, but far apart on the evolutionary ladder) use the exact same proteins to maintain their chromosomes? (Did evolution just stop?) I thought that "telomerase" meant a specific protein, but I now know it means any protein which elongates telomeres. Yeast and humans both use telomerase, but not the same telomerase. I am deleting that part of the post.
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jt Member (Idle past 5618 days) Posts: 239 From: Upper Portion, Left Coast, United States Joined: |
Thanks Ifen.
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Wounded King Member Posts: 4149 From: Cincinnati, Ohio, USA Joined: |
Hairpin telomeres cannot be replicated with normal DNA synthases, they need a special enzyme, telomere resolvase (source), to replicate and appropriately fold them. I read your source and I think there are a few salient points to note. Firstly telomere resolvase' is, like 'telomerase' a descriptive title for whatever protein is actually performing the telomere resolution. Among the proteins they identify as capable of this is a topoisomerase, hadly an unknown. Similarly the specific E. coli phage TelN resolvase they identify is said to
function through a reaction mechanism similar to that of Type IB topoisomerases and tyrosine recombinases and has structural similarity to the integrase/ tyrosine recombinase proteins. Other proteins clearly exist which can resolve the cruciform Holliday junctions. The embo J. paper you go on to discuss may well be talking about a totally different 'telomere resolvase' it need not be the same as in the source paper, a similar possible confusion as to that between human and yeast telomerase. While the paper says that the resolvase is a site-specific recombinase rather than a general Holliday junction resolvase it is surely relevant to note that a general Holliday junction resolvase might well preform the samme basic function and be a very suitable substrate for a site specific enzyme to evolve from. TTFN, WK
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Peter Member (Idle past 1501 days) Posts: 2161 From: Cambridgeshire, UK. Joined: |
Maybe both types of cell evolved from a common ancestral
strain that no longer exists. The step then would not be from one to another, but fromunkown X to Eu & Pro caryotes. Just a thought, I mean, it was a couple billion years agowasn't it?
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Wounded King Member Posts: 4149 From: Cincinnati, Ohio, USA Joined: |
This is obviously true for modern prokaryotes and eukaryotes but due to the differences mainly being due to structures the eukaryota are thought to have gained, most specifically the nucleus. Since the ancestor must either have had or not had a nucleus it must have been either pro- or eu- karyotic and the prokaryotic state is neccessarily the more primitive, although it is not neccessarily impossible that a prokaryotic bacteria could subsequently be derived from a eukaryotic ancestor.
TTFN, WK
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AdminNosy Administrator Posts: 4754 From: Vancouver, BC, Canada Joined: |
Please don't just delete. You may move the selected part and note that you have found it is in error. If you make content changes to a post then following posts may become incomprehensible.
You have a good OP and the topic is interesting others may want to follow from post 1. Please protect the integrity of the thread.
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crashfrog Member (Idle past 1489 days) Posts: 19762 From: Silver Spring, MD Joined: |
Just to clarify for Nosy, we used to have this guy here who would exessively and dishonestly redact his posts after people had responded to the things he had deleted. It's ok for you to edit after the fact to reflect things you've learned, and I think the way you did it was ok (but I'm no admin), but it's probably best that your original text survive in some form, as people might have responded to it already.
Nosy's message might have been a bit perfunctory, and I think he's nervous about redacting opening posts because, as I said, there was this guy here who we had big problems with. He's not trying to bring the hammer down, I'm sure; just trying to prevent that problem from happening again, because it was kind of a big deal at the time.
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