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Author
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Topic: "Junk DNA" as Cannon Fodder
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Frances
Member
Member # 169
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posted 06. September 2002 12:23
John's suggestions seem to be unnecessarily hostile and I wonder if John could review the posting rules for this forum?
Yet the hostility also encourages me in my argument since John's response has not done anything to address the issues raised. Your own posting is quite clear: the overall mutation rate per base pair remains fixed, so how can adding more basepairs make a difference?
Elend has raised most of the relevant issues (once again), perhaps John could be encouraged to focus on them this time and not on the messengers?
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John Bracht
Member
Member # 5
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posted 06. September 2002 19:31
Hi Frances, Elend,
My last message was not intended to be hostile, and was rather expressing some frustration I had that you guys seemed to be totally ignoring the points I made in my initial post, and making arguments I had already countered. I felt you guys were wasting my time and hadn't read my arguments carefully. I still get the impression that you don't really get what I was trying to explain, so I'll try to explain it more carefully (perhaps the problem was more in my explanation than in your understanding).
I was trying to get at the idea that there are really 2 kinds of mutation: replication-based mutation (when the wrong base gets inserted during DNA replication) versus chemical/radiation-based mutagenesis (when some sort of external environmental factor penetrates the nucleus and alters a base on the DNA). Of course, the first one will be entirely base-pair-dependent, since as one adds more DNA that has to be replicated, of course one will incur more mutations.
The second kind of mutation, I argue, is not base-pair-dependent, for the most part. Elend argues that as one increases the total amount of DNA, one also increases the "target" that the mutagenesis can impact and thus we get more mutations overall.
This is true, in some sense. If we approximate the shape of the nucleus as a sphere, we can think about the size of the nucleus (diameter) as being roughly the size of the "target" the mutagenesis will see. So imagine a ray of ionizing radiation that is shooting toward the cell. If it is within the "circle" it sees as the nucleus, it might mutate some DNA. But if it entirely misses the nucleus, it obviously can't mutate anything. Likewise, we might suppose that chemical mutagensis must diffuse into the cell and then find the nucleus, and the probability of that happening is greater if the nucleus is bigger.
We know that the equation for the volume of a sphere is V=4/3pi(r)^3. Solving for radius, we get r=cuberoot(3V/4pi). Thus, if we double the volume of the nucleus, we increase the radius of the cell by the cube root of 2. That's not very much: around 1.26. So when we increase the amount of DNA in the nucleus, it has a negligible effect on the size of the "target" for the mutagen to find.
However, imagine that you're the mutagen, and you've managed to find a nucleus whose DNA has been doubled with "junk" DNA. You have to randomly pick a spot to mutate that DNA--and it's become harder to mutate a gene relative to a cell lacking "junk" DNA. Chances are, you're going to end up mutating a piece of "junk" DNA instead of a gene.
I hope this helps explain my ideas here. Much of this is more of an intuition than anything I know with certainty (after all, this board is for novel intuitions and ideas!) and it's possible that I'm very, very wrong with these ideas. But they seem to make some sense, and I just want to explore them with you guys. I do appreciate the fact that you're trying to engage my ideas (even if I sometimes get frustrated when people seem to just be replying without having really understood my argument). I apologize for any hurt feelings, and I thank everyone who wants to comment on these ideas!
John
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Art
Member
Member # 179
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posted 06. September 2002 22:33
Two points:
1. John, have you actually compared the volume of, say, 10^6 bp of DNA with that of 10^9 bp? How does this compare with the typical size of a bacterial cell or eukaryotic nucleus?
2. Radiation, and to an extent chemical mutations, have much more dramatic effects than do replication-associated "mistakes". Of particular concern are chromosomal breaks. Increasing "junk DNA" is likely to exacerbate this problem, not protect a genome against it.
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nobody
Member
Member # 145
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posted 07. September 2002 03:14
quote:
1. I've done some research into Alu sequences, and had already learned of about 3 or 4 definite functions these sequence perform,
2. so I'm a little surprised that they were considered "junk" DNA in the article
John
1. What are some of the other functions?
2. They were careful to use the heading So-Called Junk DNA. That's a good start.
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charlie d.
Member
Member # 159
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posted 07. September 2002 10:13
May I just point out that repetitive DNA elements, Alus and LINEs in particular, are in fact responsible for genomic rearragements causing dozens of diseases, from heritable conditions (here, here, or here, to just stick to the most recent literature) to cancer?
While I feel John's hypothesis that the genotoxic effect of some mutagens (low-level chemical carcinogens, probably not radiation) might indeed be diminished by an excess of "sponge" DNA is scientifically testable (the fact that it's probably been explored already does not detract from the idea, IMO), I think it's kind of ludicrous to dwell hyperbolically on the "wonders of "junk" DNA design" when, if indeed it were designed, the manufacturer would be held liable in any US court for marketing an obviously defective product to consumers. I also notice a not-too-subtle contradiction in claiming on one side that junk DNA acts as mere "cannon fodder", a mutagen floor mop, while also wondering about its hypothetical highly sophisticated functions.
Given the inherent mutagenicity of much of "junk" DNA, an easily much better "cannon foder" design would have been non-repetitive, non-mobile DNA elements organized in entirely separate chromosomes, to avoid internal deletions, translocation, and transposition-mediated mutagenesis. Or maybe even non-DNA elements, such as dispensable, abundant nuclear proteins with high affinity for chemical carcinogens. Indeed, a productive design-based line of research could be precisely how to improve on the pitiful vulnerability of our genomes: transgenic humans with mutagen-shield proteins in their cells may not be far away!
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Art
Member
Member # 179
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posted 07. September 2002 13:31
For John's information, here's a list of genome sizes that I found. It may be a little dated, but it should still help in fleshing out the proposition that junk DNA correlates in some way with exposure to mutagens.
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Organism Genome size
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Amoeba dubia 670,000,000,000
Amoeba proteus 290,000,000,000
Ophioglossum petiolatum 160,000,000,000
Protopterus aethiopicus 139,000,000,000
Fritillaria assyriaca 124,900,000,000
Lilium longiflorum 90,000,000,000
Amphiuma means 84,000,000,000
Necturus maculosus 81,300,000,000
Pinus resinosa 68,000,000,000
Lilium formosanum 36,000,000,000
Coscinodiscus asteromphalus 25,000,000,000
Triturus cristatus 20,600,000,000
Allium cepa 18,000,000,000
Schistocerca gregaria 9,300,000,000
Paramecium caudatum 8,600,000,000
Bufo bufo 6,900,000,000
Scyliorhinus stellatus 6,000,000,000
Orycteropus afer 5,763,500,000
Leuascus cephalus 5,400,000,000
Peromyscus eremiticus 5,294,700,000
Tarsius syrichta 5,151,600,000
Cercopithecus cephus 5,141,700,000
Cercopithecus nigroviridis 5,117,100,000
Zea mays 5,000,000,000
Hordeum vulgare 5,000,000,000
Thomomys townsendii 4,934,500,000
Cercopithecus neglectus 4,796,300,000
Dypodomys ordii monoensis 4,658,200,000
Isodon macrourus 4,589,100,000
Isodon obesulus 4,554,500,000
Cercopithecus aethiops griseoviridis 4,490,400,000
Thomomys bottae 4,485,500,000
Parameles nasuta 4,426,200,000
Macropus robustus 4,396,600,000
Parameles gunni 4,357,200,000
Cercopithecus nictitans 4,342,400,000
Thomomys umbrinus 4,317,700,000
Octodon degus 4,263,400,000
Nasalis larvatus 4,258,500,000
Didelphis azarae azarae 4,238,700,000
Dypodomys spectabilis spectabilis 4,214,100,000
Tylacomys lagotis 4,209,100,000
Dypodomys ordii compactus 4,174,600,000
Macropus giganteus 4,154,800,000
Lasiorhinus latifrons 4,145,000,000
Lutreolina crassicaudata paranasalis 4,140,000,000
Galago senegalensis 4,130,200,000
Cercopithecus cynosurus 4,130,200,000
Monodelphis dimidiata 4,115,400,000
Sciurus carolinensis 4,105,500,000
Dypodomys spectabilis baileyi 4,105,500,000
Cercopithecus aethiops aethiops 4,075,900,000
Phascolomis mitchelli 4,071,000,000
Dypodomys agilis perplexus 4,066,000,000
Pongo pygmaeus 4,046,300,000
Potorous tridactilys 4,026,600,000
Marmosa pusilla 4,026,600,000
Peromyscus maniculatus 4,006,800,000
Terrapene carolina 4,000,000,000
Marmosa agilis chacoensis 3,977,200,000
Cercopithecus sabaeus 3,962,400,000
Cebus albifrons 3,927,900,000
Peromyscus crinitus 3,922,900,000
Galago crass.crassicaudatu 3,922,900,000
Gerbillus pyramidum 3,913,100,000
Cercopithecus aethiops tantalus 3,898,300,000
Galago alleni 3,878,500,000
Didelphis marsupialis aurita 3,848,900,000
Ctenomys conoveri 3,848,900,000
Cebus capucinus 3,829,200,000
Ctenomys leucodon 3,824,200,000
Nicotiana tabaccum 3,800,000,000
Pan troglodytes 3,799,600,000
Dypodomys deserti deserti 3,770,000,000
Phascolarctus cinereus 3,765,000,000
Ornitorhynchus anatinus 3,725,500,000
Ctenomys freter 3,715,700,000
Ctenomys boliviensis 3,715,700,000
Symphalangus syndactylus 3,705,800,000
Cercocebus aterrimus 3,705,800,000
Cercocebus atys 3,691,000,000
Ctenomys steinbachi 3,681,100,000
Alouatta caraja 3,676,200,000
Lemur mongoz coronatus 3,656,500,000
Dypodomys heermani californicus 3,656,500,000
Bos taurus 3,651,500,000
Cebus apella 3,631,800,000
Mesocricetus auratus 3,621,900,000
Gerbillus campestris 3,621,900,000
Cercopithecus talapoin 3,617,000,000
Erinaceus europaeus 3,612,100,000
Pongo pygmaeus 3,607,100,000
Macaca silenus 3,582,400,000
Ellobius fuscocapillus 3,582,400,000
Pan troglodytes 3,577,500,000
Ateles belzebuth 3,577,500,000
Alouatta villosa 3,577,500,000
Colobus polykomos 3,562,700,000
Sminthopsis crassicaudata 3,557,800,000
Dasyurops maculatus 3,557,800,000
Cercatetus nanus 3,557,800,000
Cercatetus concinnus 3,557,800,000
Cricetulus griseus 3,547,900,000
Macaca mulatta 3,543,000,000
Nycticebus coucang 3,533,100,000
Gorilla gorilla 3,523,200,000
Ctenomys lewisi 3,513,400,000
Macaca nemestrina 3,508,400,000
Macaca fuscata 3,508,400,000
Tachyglossus aculeatus 3,498,600,000
Sarcophilus arrisi 3,498,600,000
Lagothrix lagothricha 3,493,600,000
Papio hamadryas 3,478,800,000
Dypodomys merriami merriami 3,473,900,000
Oryctolagus cuniculus 3,469,000,000
Erythrocebus patas 3,469,000,000
Cercocebus galeritus 3,464,000,000
Mus musculus 3,454,200,000
Macaca sylvana 3,454,200,000
Papio sphinx 3,449,200,000
Dypodomys microps 3,439,300,000
Cebuella pygmaea 3,439,300,000
Hylobates agilis 3,429,500,000
Chalomys laucha 3,424,500,000
Ateles paniscus 3,424,500,000
Macaca arctoides 3,409,700,000
Macaca fascicularis 3,404,800,000
Homo sapiens 3,400,000,000
Macaca nigra 3,399,900,000
Dypodomys panamintinus leucogenys 3,399,900,000
Cavia porcellus 3,399,900,000
Callithrix jacchus 3,385,100,000
Macaca maura 3,380,100,000
Apodemus sylvaticus 3,360,400,000
Canis familiaris 3,355,500,000
Cebus nigrivittatus 3,350,500,000
Microtus agrestis 3,330,800,000
Tupaia glis 3,325,900,000
Equus caballus 3,311,000,000
Raja montagui 3,300,000,000
Hylobates muelleri muelleri 3,296,200,000
Muntiacus muntjak muntjak 3,281,400,000
Saimiri sciureus 3,251,800,000
Perodicticus potto potto 3,251,800,000
Ovis aries 3,251,800,000
Perodicticus potto edwardsi 3,246,900,000
Hapalemur griseus griseus 3,242,000,000
Hylobates klossi 3,222,200,000
Holochilus vulpinus 3,217,300,000
Ateles geoffroy 3,207,400,000
Lepilemur mustelinus 3,202,500,000
Lama glama 3,202,500,000
Hapalemur simus 3,202,500,000
Hapalemur gr.occidentalis 3,202,500,000
Galago crass.argentatus 3,202,500,000
Lama vicugna 3,197,600,000
Capra hircus 3,197,600,000
Hylobates moloch 3,192,600,000
Hylobates lar 3,192,600,000
Apodemus flavicollis 3,177,800,000
Lama huanacus 3,163,000,000
Hapalemur gr.olivaceus 3,138,300,000
Clethrionomys rufocans 3,138,300,000
Hapalemur gr.alaotrensis 3,133,400,000
Ctenomys opimus 3,118,600,000
Akodon xantorhinus 3,118,600,000
Sus scrofa 3,108,700,000
Xenopus laevis 3,100,000,000
Rattus rattus 3,093,900,000
Lemur macaco rufus 3,084,100,000
Muntiacus reevesi 3,074,200,000
Microcebus murinus 3,074,200,000
Lemur catta 3,069,300,000
Apodemus agrari 3,069,300,000
Chalomys musculinus 3,059,400,000
Lemur mongoz mongoz 3,049,500,000
Lemur macaco fulvus 3,049,500,000
Chincilla laniger 3,029,800,000
Akodon olivaceus 3,010,000,000
Ellobius lutescens 2,990,300,000
Neotoma floridana 2,955,800,000
Microtus montanus 2,955,800,000
Ellobius talpinus 2,955,800,000
Dypodomys heermani tularensis 2,955,800,000
Bolomys obscurus 2,945,900,000
Camelus dromedarius 2,926,200,000
Rattus norvegicus 2,900,000,000
Tadarida brasiliensis 2,896,600,000
Akodon molinae 2,876,800,000
Chalomys laucha laucha 2,862,000,000
Cabreramys sp. 2,847,200,000
Clethrionomys rutilus 2,842,300,000
Microtus arvalis 2,837,300,000
Arvicola terrestris 2,837,300,000
Camelus bactrianus 2,817,600,000
Meriones unguiculatus 2,807,700,000
Phyllotis griseoflavus 2,797,900,000
Eligmontia sp. 2,792,900,000
Scapteromys aquaticus 2,768,300,000
Peromyscus floridanus 2,768,300,000
Clethrionomys glereolus 2,768,300,000
Oryzomys nigripes flavescens 2,763,300,000
Chalomys callosus callosus 2,763,300,000
Akodon mollis 2,728,800,000
Loligo loligo 2,700,000,000
Limulus polyphemus 2,700,000,000
Carcarias obscurus 2,700,000,000
Microtus ochragaster 2,699,200,000
Akodon dolores 2,694,200,000
Microtus longicaudatus 2,659,700,000
Oxymycteris rufus platensis 2,630,100,000
Caiman crocodylus 2,600,000,000
Acomys cahirinus 2,585,700,000
Microtus subterraneus 2,546,200,000
Thomomys talpoides 2,536,300,000
Eumops perotis perotis 2,536,300,000
Muntiacus muntjak vaginalis 2,521,500,000
Microtus oregoni 2,511,700,000
Parascaris equorum 2,500,000,000
Natrix natrix 2,500,000,000
Microtus pennsylvanicus 2,477,100,000
Microtus duodecimcostatus 2,477,100,000
Microtus oeconomus 2,437,600,000
Microtus californicus 2,432,700,000
Akodon azarae 2,393,200,000
Callicebus cupreus 2,264,900,000
Pipistrellus kuhli 2,260,000,000
Callicebus torquatus 2,225,500,000
Eptesicus fuscus 2,220,500,000
Pteropus giganteus 2,186,000,000
Barbastella barbastellus 2,171,200,000
Thomomys monticola 2,136,600,000
Myotis myotis 2,116,900,000
Boa constrictor 2,100,000,000
Pipistrellus savii 1,973,800,000
Rhinolophus ferrumequinum 1,929,400,000
Lampreta planeri 1,900,000,000
Danio rerio 1,900,000,000
Myotis mistacinus 1,899,800,000
Rhinolophus hipposideros 1,894,800,000
Rhinolophus euryale 1,840,600,000
Myotis capaccinii 1,820,800,000
Aplysia californica 1,800,000,000
Miniopterus schreibensi 1,707,300,000
Python reticulatus 1,700,000,000
Cyprinus carpio 1,700,000,000
Erysiphe cichoracearum 1,500,000,000
Cerebratulus 1,400,000,000
Spisula solidissima 1,200,000,000
Gallus gallus 1,200,000,000
Glycine max 1,115,000,000
Strongylocentrotus purpuratus 900,000,000
Musca domestica 900,000,000
Crassostrea virginica 700,000,000
Aurelia aurita 700,000,000
Lycopersicon esculentum 655,000,000
Oryza sativa 400,000,000
Medicago truncatula 400,000,000
Fugu rubripes 400,000,000
Tetraodon nigroviridis 350,000,000
Schistosoma mansoni 270,000,000
Sarcocystis cruzi 201,000,000
Tetrahymena pyriformis 200,000,000
Prosimulium multidentatum 200,000,000
Ciona intestinalis 200,000,000
Chironomus tentans 200,000,000
Paramecium aurelia 190,000,000
Drosophila melanogaster 180,000,000
Chlamydomonas reinhardtii 100,000,000
Caenorhabditis elegans 100,000,000
Brugia malayi 100,000,000
Arabidopsis thaliana 100,000,000
Toxoplasma gondii 89,000,000
Eimeria tenella 70,000,000
Eimeria acervulina 70,000,000
Trypanosoma brucei 35,000,000
Navicola pelliculosa 35,000,000
Dictyostelium discoideum 34,000,000
Emericella nidulans 31,000,000
Aspergillus nidulans 31,000,000
Plasmodium falciparum 25,000,000
Plasmodium berghei 25,000,000
Entamoeba histolytica 20,000,000
Schizosaccharomyces pombe 14,000,000
Saccharomyces cerevisiae 12,067,280
Giardia lamblia 12,000,000
Giardia intestinalis 12,000,000
Escherichia coli 4,639,221
Mycobacterium tuberculosis 4,397,000
Bacillus subtilis 4,170,000
Synechocystis sp. strain PCC6803 3,573,470
Mycobacterium leprae 2,800,000
Haemophilus influenzae 1,830,137
Helicobacter pylori 1,667,867
Methanococcus jannaschii 1,664,974
Borrelia garinii 953,000
Borrelia afzelii 948,000
Borrelia burgdorferi 946,000
Mycoplasma pneumoniae 816,394
Mycoplasma genitalium 580,000
Human immunodeficiency virus type 1 9,750
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I'll let John (and others) match these names with more commonly-understood identifications.
If the moderator thinks it more appropriate to replace this list with a link, here it is:
http://www.cbs.dtu.dk/databases/DOGS/abbr_table.bysize.txt
I'd note that, to a first approximation, larger eukaryotic genome sizes will correlate with higher repetitive DNA contents. Thus, as an example, Arabidopsis probably has 10-20% repetitive DNA, and the difference between Arabidopsis (10^8 bp) and tobacco (Nicotiana tabacum, 3.8x10^9 bp) is almost entirely "junk DNA".
Art
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Frances
Member
Member # 169
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posted 07. September 2002 17:48
Hi John,
Thanks for your response. Let me try to explain to you what I believe to be mistaken in your argument about radiation. You suggest that a larger genome would not be affected proportionally. What if the genome is twice as long? Seems to me that the genome is now exposed to twice the radiation.
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Elend
Member
Member # 326
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posted 08. September 2002 05:22
Frances to John
quote:
What if the genome is twice as long? Seems to me that the genome is now exposed to twice the radiation.
I think John already tried to address that issue here: (btw, thanks John for the explanatory post)
quote:
We know that the equation for the volume of a sphere is V=4/3pi(r)^3. Solving for radius, we get r=cuberoot(3V/4pi). Thus, if we double the volume of the nucleus, we increase the radius of the cell by the cube root of 2. That's not very much: around 1.26. So when we increase the amount of DNA in the nucleus, it has a negligible effect on the size of the "target" for the mutagen to find.
I wouldn't say is negligible though. It simply depends sub-liniarily (cubic root of length) on the DNA size. But I have to say that I am not sure if one should consider the volume of the sphere ("cell") as a target or the area of the sphere - case in which the dependency is square root. This is not significant here.
YET: The same dependency applies to both "junk" and coding DNA. Assuming that radiation can be described as a uniform probability function over space, the volume occupied by the coding DNA does not change as the "junk" DNA varies. This means that the absolute number of mutations in the coding DNA does not change.
Now if one could somehow show that the "junk" DNA shields the coding DNA from mutations (say the "target" is the sphere surface, and "junk" DNA is more likely found at the exterior of this volume) then that would indeed be something interesting.
John said:
quote:
However, imagine that you're the mutagen, and you've managed to find a nucleus whose DNA has been doubled with "junk" DNA. You have to randomly pick a spot to mutate that DNA--and it's become harder to mutate a gene relative to a cell lacking "junk" DNA. Chances are, you're going to end up mutating a piece of "junk" DNA instead of a gene.
That is true for one specific mutagen. But for the case of radiation, once the target grows, more mutagens reach the DNA - as said before the number of mutations in the coding DNA hardly changes. "Junk" DNA has effect only on mutagens that target at cell level (are there any such mutagens?) - say a constant number per cell (viruses, chemical?).
[ 08 September 2002, 05:32: Message edited by: Elend ]
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peroxisome
unregistered
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posted 08. September 2002 07:26
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What if the genome is twice as long? Seems to me that the genome is now exposed to twice the radiation.
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quote:
We know that the equation for the volume of a sphere is V=4/3pi(r)^3. Solving for radius, we get r=cuberoot(3V/4pi). Thus, if we double the volume of the nucleus, we increase the radius of the cell by the cube root of 2. That's not very much: around 1.26. So when we increase the amount of DNA in the nucleus, it has a negligible effect on the size of the "target" for the mutagen to find.
This strikes me as bizarre. In fact, the volume of the DNA doubles, when the amount of DNA doubles. This is a linear relationship.
You are correct to point out the relationship between the volume of a sphere and increase in radius, but it seems to me to be of doubtful relevance. After all, when you double the volume of a sphere, you have doubled the volume of the sphere, and the effect on radius is neither here nor there.
Biologically, it is less helpful than that, especially in eukaryotes, because "junk DNA" is normally packed and inaccessible, whereas active DNA is open to attack.
The point previously made by charlie d. about the inherent problems associated with "junk DNA" have some force. Indeed, I believe that there is thought that "junk DNA" evolved because of the selective advantage it provides through enhancing DNA mutagenesis.
per
edit: typos, phat phingerz
[ 08 September 2002, 07:29: Message edited by: peroxisome ]
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Leonid Andreev
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Member # 282
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posted 09. September 2002 04:33
John’s idea is sound in itself. If you own two houses, chances that you will find yourself in need of a shelter after an accidental fire are twice less. However, while human-beings may afford having more than one house, the Nature cannot afford the extravagance of synthesizing and maintaining a wealth of “junk DNA” simply to be able to make up for possible mutations. One can easily suggest hundreds of better ways for offsetting mutagenic effects that the Nature could effectively employ. At least, there is no doubt that Deinococcus radiodurans, a record-breaker in ionization radiation resistance, with its DNA consisting of over three thousand genes and three million base pairs, has a powerful DNA reparation mechanism and does not use a “junk DNA” hedging. I would say that the concept proposed by John serves well to explaining the effect but not the cause.
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Elend
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Member # 326
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posted 09. September 2002 04:56
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If you own two houses, chances that you will find yourself in need of a shelter after an accidental fire are twice less.
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Excuse me, but that is a bad analogy. First, we are locked in our "coding DNA" house. If the accident happends, we burn. Second, if you own N houses, the chances of having an accidental fire in any of them increases N fold. ![[Frown]](frown.gif) In any case our "coding DNA" house (us included) is not safer. Simple probabilistic calculus gives no advantage for "junk DNA". One needs to look deeper at the actual properties of the system to draw adequate conclusions.
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Leonid Andreev
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Member # 282
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posted 09. September 2002 13:47
Elend,
1. First of all, you obviously misread my analogy as it was not about a probability of an accidental fire – it was about the probability of losing BOTH homes to an accidental fire. These are two different things, as I understand it.
2. The fact of our being locked in our “coding DNA” house should not rob us of common sense and logical thinking: John’s idea is absolutely sound and effective, although collateral.
3. There is no “simple probabilistic calculus” for DNA. As you have justly noted, “one needs to look deeper at the actual properties of the system to draw adequate conclusions”.
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Leonid Andreev
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Member # 282
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posted 09. September 2002 17:16
Since this discussion has been dwelling mostly on probability issues, leaving aside the biological aspects of the problem, I thought that it would be appropriate if I offer an explanation to “junk DNA” from a purely biological standpoint, which may also give a fresh slant to the discussion. Some bits of the whole concept were disclosed by me in print some 15-20 years ago, but here I will present an evolutionist’s brief on the phenomenon of “junk DNA”. My flatness and lack of substantiation or references is solely due to considerations of brevity, which may be even for better as it will allow keeping a tight focus of the problem.
Let me start with a thesis which should not seem to be groundless. It concerns the role of biological membrane lipids. At a population level, lipid synthesis occurs in a quasi-equilibrium mode in such a way that a ratio between particular lipids depends on ratios between coenzymes and cofactors that are involved in lipid biosynthesis (cf. for example, Andreev, L. et al. In: The Staphylococci. J. Jeljaszewicz (Ed.). Gustav Fisher Verlag, Stuttgart, New York, pp. 151-155, 1985; Andreev, L. In: Rapid Methods and Automation in Microbiology and Immunology. K.-O. Habermehl (Ed.), Springer Verlag, Berlin, Heidelberg, New York, pp. 265-273, 1985.). These include the ratios between: oxidized and reduced pyridine-nucleotides; acetylcoenzyme A and free coenzyme A; methionine and homocysteine; as well as their analogs – carriers of C1 fragments, leucine, isoleucine and valine, and respective deaminized derivatives that serve as sources for synthesis of iso- and antheiso-fatty acids. When continued, this list would include most of the substances known as vitamins. Built into membrane, lipids convey the information about contents of co-enzymes and cofactors in cytosol to membrane proteins which are responsible for most of the construction and destruction functions needed to support life. Thus lipids facilitate the adjustment of their activity to a level and composition of low-molecular intermediaries of membrane enzymatic processes. Membrane lipids are known to be capable to alter the activity of membrane proteins by means of conformational effects and thus to ensure strict coordination between cytosol composition and biological membrane activity. For instance, iso- and anteiso-fatty acids interact, through the effect of London’s quantum mechanical forces, with valeic, leucinic and iso-leucinic residues of membrane proteins. This explains why a lipid composition of most prokaryotes strictly depends on a physiological condition of a cell population.
Let us see what the above means in the context of cells of rapid-growing Gram-negative simple shape bacteria. As bacteria have no endoplasmic reticulum, we can assume that membrane proteins are exposed, through lipids, to the same effect determined by the ratio between co-enzymes and cofactors, which, due to diffusion occurring at biological growth temperatures, are equally represented throughout the intracellular space. Therefore, membrane proteins join into membrane protein ensembles that are evenly distributed on a cytoplasmic membrane, which may make them easily detectable with freeze-etching electronic microscopy. A reasonably uniform individual set of membrane proteins includes proteins whose functions are antipodal in the view of the physicochemical requirements; hence they provide low output but bear a high potential efficiency. This is characteristic of cells of such bacteria as, for instance, cholera, plague, coliform bacteria, rapid-growing Pseudomonas, as well as some other groups of bacteria which, given enough substrate and adaptation, are capable for explosive growth..
An alternative organization of enzymatic processes in membrane is inherent in so-called oligotrophs – extremely slowly growing Gram-negative bacteria with optimal growth in nutrient-limited conditions. Their cells commonly have a complex, elaborate structure. Examples of oligotrophic organisms are: stalked bacteria, prostecobacteria, hyphomicrobial and other morphologically differentiated bacteria capable for growth on media with limited nutrients (as well as in natural environments). An increase in growth substrate concentration results in expressed involutional changes: stopping of growth, lysis, etc. Rather than relying on a total capacity of membrane enzymatic processes, as in the earlier discussed case, these bacteria need a high metabolic efficiency and the ability to fully utilize those scarce amounts of substrate that are available in ecological niches which they inhabit. Unlike E. coli and V. cholera, oligotrophs have no OmpF-type outer membrane porins that allow the passive diffusion of substrates across the outer membrane. They have energy-gated outer membrane channels for specific substrates.
The organization of membrane enzymatic processes in oligotrophic slowly-growing bacteria is conceptually different from that of rapid-growing bacteria. Their membranes have vast sections that perform solo in carrying out highly specialized functions, and that is why they grow slowly – as various functions are spatially separated, and their coordination requires having special mechanisms in place. Many of specialized sections of oligotroph membranes, such as, for instance, the sections responsible for transport and ATP aerobic synthesis, require opposite physical conditions of membranes. Thus, we are speaking of two types of system: one is well-managed but poorly regulated, another is poorly managed but highly regulated. In rough outline, the whole world of prokaryotes may be described as a sort of fuzzy band bounded with bacteria with the afore-mentioned opposite living systems. Practically any taxonomically homogenous genus of bacteria can be presented as a series constrained by slow-growing and rapid-growing species. For instance, in Pseudomonas genus, P. aeruginosa is, in fact, oligotrophic, although it does not exactly meet the criteria for oligotrophs.
Oligotrophs present that rare case in biology when purely physical notions can do the job of explaining such a purely biological quality of organisms as morphogenesis. By creating lateral cavities (buds, prosteca, etc.) in the cytoplasmic space, bacteria acquire a possibility to create diffusion resistance in the intraplasmic space and thus to achieve the required functional accordance between activities of specific membrane sections and concentration of low-molecular metabolites in respective parts of cytosol. However, having this evolutionary improvement in place took its toll on oligotrophs’ strength, resulting in asthenia: extreme oligotrophs’ growth may take tens of days even in optimal conditions.
The path between Scylla and Charibda of prototrophs and oligotrophs is used by eukaryotes. It consists in creation of endoplasmic membrane compartments that allow for reaching the maximum accordance between specific membranes and the circumambient pool of low-molecular metabolites. This path became possible due to: the emergence of endoplasmic reticulum, the resulting autonomism of energy-providing membrane sections in the form of autonomous energy-producing systems – mitochondria, and – as a final phase of construction of a new in kind biological system – emergence of a nuclear membrane that bounded the DNA. (It would be logical to assume that the first eukaryote came from the most asthenic oligotrophs.)
Unlike prokaryotes, eukaryotes represent a system where the complementarity principle cannot be implemented in regulation and management: a gene expression has to be coordinated with activities in all of those biochemical and biophysical compartments where the respective gene-coded agent’s activity will be expressed. Given the complexity of compartmentalization in eukaryotic cells, this process is extremely complicated. That is why the Nature has provided each gene or group of functionally close genes with a “support staff” – the so-called repetitive DNA – to carry out basic, trivial functions of activation of the involved systems. However, repetitive DNA cannot be isolated into a separate block, as a specialty of a “support staff” for particular genes is based on a combination of varied basic trivial functions. Thus, when we say “junk DNA”, we, in fact, are referring to a vitally important management team that provides for successful operation of subordinate genes. This explains why a eukaryote genome cannot function at a circular DNA level.
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charlie d.
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Member # 159
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posted 09. September 2002 18:11
Leonid:
how would your hypothesis explain eukaryotes, even metazoa, with extremely compact genomes (e.g. fugu)? The question is not whether some repetitive DNA elements, or non-coding DNA in general, have a function (obviously some do), but why our genome is >90% made of it. Do we need all 3 gigabasepairs of repetitive/non-genic DNA? If so, how does the pufferfish do without? If not, why do we have it and not the pufferfish?
[ 09 September 2002, 18:28: Message edited by: charlie d. ]
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Leonid Andreev
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Member # 282
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posted 09. September 2002 21:22
Charlie,
In most bacteria, yeasts and other eukaryotes, the ratio between proteome and genome is close to 1. In humans, the ratio is much higher, which should result in exponential growth of repetitive DNA if it indeed plays the role explained in my hypothesis. My previous posting does not pursue exploring an issue of why a human genome is only an order of magnitude larger and more complex than that of fungi and smaller than that of pufferfish. One cannot get the understanding of a mechanism quality by counting its parts.
[ 09 September 2002, 21:23: Message edited by: Leonid Andreev ]
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