Problems with Chromosomal Evolution - From Circular to Linear

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 HERETo 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 protein
2. 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 endcapsThe 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,
JTThis message has been edited by JT, 08-20-2004 03:29 PMThis message has been edited by JT, 08-22-2004 08:26 PMThis message has been edited by JT, 08-23-2004 11:49 AM

Circular chromosomes have no ends which need to be protected, so do not need telomeres, and thus do not need telomerase. 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." 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. It is my contention that in the case of this system, it would have had to come about in one fell swoop. 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.

Thanks. From http://www.ym.edu.tw/ig/cwc/end_troubles/End_Troubles.htm:

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Perhaps the most prominent issue is how a linear bacterial chromosome is replicated...The main issue is at the termini, which normal replicating machinery cannot fully replicate.[emphasis mine]

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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:

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The molecular details by which telomere resolution occurs remain to be established. Our data indicate, however, that the target site for the reaction is specific: an inverted repeat of the same size and base composition as the lp17 left telomere, but with an unrelated sequence, was completely inactive in telomere resolution. - From http://embojournal.npgjournals.com/...ontent/full/20/12/3229

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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. 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

In the opening post, I said: 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.

Thanks Ifen.

That makes sense. I restored the deleted portion and added a bracketed statement explaining the error.

Yeah, that would be annoying in an infuriating way. Nosy's post was slightly terse, but I completely understand why now. No hammer felt...

[deleted repeat post]This message has been edited by JT, 08-23-2004 12:35 PM

Thanks. If a circular chromosome broke, one of two things would happen to the cell: either it would survive, or it would die. There is no better/worse, faster/slower, it is pass/fail. If an enzyme was present which was not functional, even if it was extremely close, the cell would still die. There would be no co-evolution - since the cell would die if the enzyme was not working all the way, there would be no selective pressures able to keep around almost functional proteins.Also, if a line of cells (without the mechanisms necessary to maintain a linear chromosome) had the tendency to convert to linear chromosomes and die, they would soon lose that trait via natural slection. NS would simply kill any cells which had the trait, and soon there would be a purebred strain of firmly circular cells. There is no evidence for this type of system - it is purely speculative (to the best of my knowledge). That could have happened, hypothetically, but there are still a couple problems. That still doesn't solve the problem of how a chromosomal protection system was created, it just pushes it back further on the timeline.Second, once the cells had developed circular chromosomes, natural selection would favor cells which cut the production of the useless enzymes, freeing up valuable resources for other needs. By the time linear chromosomes came again, the system for maintaining them would have degraded substantially or disappeared, and would likely not work. And I look forward to your response.

Looks like we cross posted. Does my post cover your argument enough? If not, I can be more thorough.

Good luck moving! We'll be awaiting your return. I'll try to do that, and the example you came up with is an interesting possibility that I need to think about...(I'll post about it when I've thought it through satisfactorily)

No apology needed. M-w online defines "terse" as: "1 : smoothly elegant 2 : devoid of superfluity," both of which are good things. I didn't feel chastised, just corrected.

Could you quote some more of the article which supports that (I don't have access to the full article)? The part you quoted only said that the reaction mechanism was "similar," not that the proteins are identical. (I'm not trying to be pedantic - the context probably makes the meaning of that statement very clear, but without the context it is unclear) Arggh! I made the same stupid mistake twice in a row. I will not do that again. But you are probably right; there are quite possibly telomere resolvases that are not site specific.

If linear chromosomes evolved from circular chromosomes, it would have happened like that. What I am saying is that an occurence like that would be by complete chance - there could not be a gradual evolution of a system of preservation. If such a system was not present in full functionality when a cell's chromosome became linear, the cell would die.Are you saying that even if the system was complex, it would have had enough chances to develop that odds are it would have? Several things here; first, the protection system still would have had to evolve, which I think is implausible. If the protection of a linear chromosome is at its simplest a complex system, it evolving in the first cell with DNA is even more implausible than it evolving in a line of cells already having DNA. All you are doing is pushing the timeline back - it is not an explanation of how linear chromosomal protection could have evolved.Second, even if such a system was present in extremely early cells, the chances of it surviving very long after it stopped being needed is low. Cells that didn't have to create/maintain the useless system would be less pressed for resources, and the system would soon degrade into non-functionality.Well, I'm glad I only missed properly covering two points from your post. Two isn't a very big number, anyway... Cool.

I don't think it is a red herring, it is integral to some things. Here is an (exagerated) example: There is a certain protein composed of 100,000,000 amino acids, and it is somehow known that it could not have evolved in more than 1 generation (I am not claiming the stuff with telomeres is near that, this example is hugely exagerated). What would that make you think about evolution, and why? But in cells there is not a simple gradient from simple to complex - an enzyme either works or it doesn't. Natural selection sees no difference between "not working" and "almost working." Enzymes are hurdles - they cannot be taken by small amounts; the whole thing has to be cleared in one jump. I'm aware of that. Exactly - and I think that the systems in question couldn't have gotten from non-existent to working, and would have been discarded.