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Member (Idle past 5626 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 | |||||||||||||||||||
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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Loudmouth Inactive Member |
quote: I think someone mentioned stem-loops earlier, but I found an article (not primary) that discussed this process. In this article Dr. de Lange speaks about the use of telomeric loops (t-loops) as a means of stopping degradation of linear DNA. This type of end protection does not require telomerase or any enzymes at all. The mechanism relies on DNA bending back on itself forming a type of stem-loop. A few excerpts from the article:
But things started out very simply, de Lange says. She suggests that tiny structures called telomeric-loops (t-loops), which she and her collaborators discovered four years ago, are actually remnants of the original telomere system that served to protect the ends of the first linear chromosomes found in early microorganisms. The investigators have shown that without these little loops, cells mistake the exposed chromosome ends for sites of DNA damage and when they attempt to repair them, the cells die. If the chromosomes of a microorganism, such as the bacterium that gave rise to eukaryotes, were linear, a t-loop could easily be formed from just a few repeats at the end of the chromosome, de Lange says. All the enzymes to make t-loops were already available; they were used for regular DNA replication in bacteria. When E. coli is replicating its DNA, occasionally the newly synthesized fork collapses, leaving the end of the new DNA hanging out of a half-replicated E. coli genome. So it would seem that the telomeres and telomerases were not necessary for the formation of linear DNA. Also, de Lange also mentions that telomerases could have developed later as a more effecient and dynamic system (control by committee as de Lange puts it). Also, we see other solutions in higher taxa, such as in Drosophila.
Annu Rev Genet. 2003;37:485-511. Retrotransposons provide an evolutionarily robust non-telomerase mechanism to maintain telomeres. Pardue ML, DeBaryshe PG. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. mlpardue@mit.edu Telomere molecular biology is far more complex than originally thought. Understanding biological systems is aided by study of evolutionary variants, and Drosophila telomeres are remarkable variants. Drosophila lack telomerase and the arrays of simple repeats generated by telomerase in almost all other organisms; instead, Drosophila telomeres are long tandem arrays of two non-LTR retrotransposons, HeT-A and TART. These are the first transposable elements found to have a bona fide role in cell structure, revealing an unexpected link between telomeres and what is generally considered to be parasitic DNA. In addition to providing insight into the cellular functions performed by telomeres, analysis of HeT-A and TART is providing insight into the evolution of chromosomes, retrotransposons, and retroviruses. Recent studies show that retrotransposon telomeres constitute a robust system for maintaining chromosome ends. These telomeres are now known to predate the separation of extant Drosophila species, allowing ample time for elements and hosts to coevolve interesting mechanisms. emphasis mine The fruit fly actually uses viral genetic sequences to insert repetitive sequences at the end of their linear DNA. This is more evidence that telomerases are not needed and other solutions exist. My conclusion is that assuming telomeres and telomerases are NECESSARY for linear DNA formation is not a correct assumption. Two other systems are found within nature, and possibly more exist that have not yet been discovered. Also, with a t-loop system in place it is very possible that another system was able to coevolve and replace the less ellegant system. As metazoans evolved they needed to control cell replication to prevent certain tissue types from dominating the organism. This requires a level of control not seen in the t-loop system, but is seen within a telomerase control system.
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Loudmouth Inactive Member |
quote: And this sort of jump has been observed. Take the nylong bug, for example. A one base insertion caused a frame shift that resulted in a functional enzyme that cleaved one of the byproducts of nylon production (reference). So actually new enzymes with novel activity are able to arise in a one-time mutational event. You are correct in stating that natural selection can not select between "not working" and "almost working" (which are actually the same thing) but it can select against "suddenly working" and "not working". Given this example, it is quite possible that the first telomerase could have arisen from one single mutation that was not planned and accidental just as we have observed in the nylon bug.
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Loudmouth Inactive Member |
quote: The host cell could use the viral long tandem repeats (LTR's) through retrotrasposition to solve the problem of end deletion in linear DNA replication. A similar mechanism is used in Drosophila, although the whole viral genes are used instead of LTR's.
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Loudmouth Inactive Member |
quote: There are some tantalizing hints that this work has been done, but I haven't been able to find free access to any of the primary literature as of yet. From The Rockefeller University » testpost for LDAP authorlogin :
E. coli has a mechanism to deal with this. Enzymes take the extruded DNA and reinsert it back into the genome. This reaction is similar to the formation of a t-loop. Through regular DNA synthesis, you have the chance to extend the end of the inserted DNA in the t-loop, just as the telomerase enzyme does, de Lange says. All you need to get this primitive telomere system to work are a few repeats at the end of the linear DNA. As proof of this notion, de Lange points to several proteins that currently act at telomeres that have evolved from the enzymes in E. coli that are involved in replication restart events. There are also prokaryotic relics of this system de Lange calls them living fossils in which linear chromosomes have repeats of varying sequences and sizes at their ends. These living fossils survive with linear chromosomes because they have miniature t-loops, de Lange says. And from de Lange's Rockefeller university page The Rockefeller University : (this is just a snippet, the whole description is worth a read)
Our long-term goal is to understand how the human telomeric complex executes its two main functions: to protect chromosome ends and mediate their replication. Telomeres shield chromosome ends from extensive degradation and fusion and allow cells to discriminate between broken DNA and natural chromosome ends, thus ensuring that DNA damage checkpoints are not activated in undamaged cells. Our research is aimed at determining how cells distinguish natural chromosome ends from DNA breaks and what happens when telomere protection is lost. . . The protection of chromosome ends is mainly executed by TRF2, a TRF1-related telomeric DNA-binding factor. TRF2 recruits additional proteins to the telomere, including the TRF2 interacting protein hRap1 and the Mre11 recombination repair complex. Loss of TRF2 leads to immediate deprotection of chromosome ends as evidenced by the loss of the telomeric 3'-tail and fusion of chromosome ends. . . We found that removal of TRF2 from human telomeres and the ensuing deprotection of chromosome ends induced immediate premature senescence, even though the telomeric tracts remained intact. This premature senescence was indistinguishable from replicative senescence and could be mediated by either the p53 or the p16/RB pathways. Telomere deprotection also induced a growth arrest and senescent morphology in mouse cells. de Lange seems to be the most active researcher on the evolution of early telomere systems and human telomere control, at least during my brief searches. I have found some of her papers but they are not free-access. I could order through my job, but it really wouldn't be that ethical. I will keep looking, but I thought it might go faster if two people were looking down the same path. If anyone else has access to more of de Lange's work feel free to post it here.
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