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Old 01-17-2002, 01:50 PM   #21
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Quote:
Originally posted by tribalbeeyatch:
<strong>I can't tell whether everybody is trying to say the same thing or there is some disagreement here. A frameshift within a gene will profoundly alter that gene, but other genes up or downstream of the frameshift will still be in frame with their start codons, so they will still be expressed normally.</strong>
Unless of course, those other genes are in an operon whose expression depends on the expression of the (now mutated) first gene. Then they wouldn't be expessed normally (if at all). But, you are correct, their reading frames would not be affected by the mutation in the other nearby gene.
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Old 01-17-2002, 01:54 PM   #22
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In many cases the defect is either repaired or the cell dies:

From The New England Journal of Medicine: volume 343, 1566-68, November,2000:

Quote:
Errors in DNA that arise during normal replication of the molecule (nucleotide mismatches) or that are induced by ionizing radiation or genotoxic drugs can cause mutations in coding sequences or breaks in double-stranded chromosomal DNA. If the nucleotide mismatch is not repaired before a round of DNA replication occurs, that mutation is transmitted to daughter cells. An unrepaired break in double-stranded DNA can cause a mitotic catastrophe when the cell attempts to segregate broken chromosomes. Studies of yeast have identified genes that sense damaged DNA and cause the arrest of the cell cycle, which allows time for the molecular defect to be repaired. These genes operate at several specific "checkpoints" in the cell cycle as a means of ensuring genomic integrity before DNA is synthesized.
Also, base changes or deletions in somatic cell lines will not be transmitted to off-spring, whereas germ-line changes may be if the mutation is compatible with survival and reproduction.

A base deletion in the cell of an eye could be transmitted to future generations of that cell line but not to the off-spring of the organism itself.

[ January 17, 2002: Message edited by: rbochnermd ]</p>
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Old 01-17-2002, 03:06 PM   #23
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Quote:
Originally posted by:davidH

Yo, what would happen if one base in that cell was removed? Like from anywhere along the strand.
Would that change the whole DNA strand? Like change all the bases in 3s?
I'm sure there must be something to stop that happening you know what it is?
Thanks.
&lt;nitpick&gt;
While everyone is giving great answers as to what would happen in a gene, it seems everyone has overlooked the fact that he's asking about a single base being removed from the entire genome.

Even correcting for a base pair removal, I don't think it would affect the functionality of a cell all that much. While the entire genome of a multi-cellular organism , isn't only 2% to 3% of the genes that are used? So, unless the base pair deletion occured in that crittical 2 to 3 percent, IN a promoter/enhancer or sequence which coded for a protien, the deletion really wouldn't matter.
&lt;/nitpick&gt;

-Liana
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Old 01-17-2002, 03:59 PM   #24
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The point is, if a frameshift occurs, it scrambles the rest of that particular sequence. Where there were start/stop codons are now those for amino acids, and vice versa, and all code for different amino acids now.
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Old 01-17-2002, 04:09 PM   #25
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Quote:
Originally posted by CodeMason:
<strong>The point is, if a frameshift occurs, it scrambles the rest of that particular sequence. Where there were start/stop codons are now those for amino acids, and vice versa, and all code for different amino acids now.</strong>
Again, I'm not sure that everybody is on the same page here. When you say "the rest of that particular sequence", are you referring to the rest of a gene in which the frameshift occurs or the rest of the chromosome? The former is true, but the latter isn't.
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Old 01-17-2002, 04:21 PM   #26
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Quote:
Originally posted by davidH:
<strong>Wow that's quite alot of bases in a cell!

Yo, what would happen if one base in that cell was removed? Like from anywhere along the strand.
Would that change the whole DNA strand? Like change all the bases in 3s?
I'm sure there must be something to stop that happening you know what it is?
Thanks.</strong>
Poor, poor David. All these people telling you the wrong things. Actually, everyone is on the right track, just minus a lot of details. First of all, there is what's known in molecular biology as an open reading frame (ORF). ORFs are segements of DNA that code for proteins, and it is only within an ORF that an indertion/deletion is going to make a profound difference in function, by virute of a frameshift. In prokaryotes, something around 90% of the genome consists of ORFs; the rest is mostly promoters, operators, and other regulatory sequences. Though an insertion/deletion in one of these regions might affect how that region functions, it will not cause a drastic frameshift in any proteins. In fact, it's possible that such insertions/deletions might change the regulatory structure in such a way as to make the organism better adapted. And there are other sequences, like introns (rare but not non-existant in prokaryotes) and spacers between genes that are inconsequential.

In eukaryotes, a much, much smaller percentage of the genome consists of ORFs. In yeast, it's about 68%; in the malarial parasite, 33%; in C. elegans (a roundworm) 27%; in C. intestinalis (an invertebrate chordate) about 13%. In humans, it's much smaller, only a few % I think but I can't find a reference off hand. All of the extra DNA here that does not consist of ORFs is what is often termed "junk" DNA, which is a misleading term because it doesn't do justice to what we know about this DNA. Much of it is in the form of introns. Introns are "intergenic" sequences that separate ORFs known as "exons". A gene is typically made up of many exons, and these exons are spliced together after the introns are removed to make a mature transcript that will code for a protein. So to get back to your question, if an insertion/deletion occurs in an intron, it will usually make no difference. If it occurs in an exon, it will cause a frameshift in the part of the protein downstream from that particular exon, which may be a little, or it may be a lot. But it will have no effect on any other proteins. Now the thing is, introns are usually much bigger than the exons, depending on who you're talking about. In those cases above, much of the difference in ORF percentage is due to the fact that more "advanced" organisms tend to have longer introns. In most cases, the intron/exon structure is the same in humans, for example, as it is in these other organisms, (it's because we're related by common descent in case you didn't know) but the introns in humans are much longer. This is presumably because fast replicating organisms like yeast have great selective pressure to remove this extra DNA, whereas we don't. (I hope you're paying attention, because there's going to be a test on Monday.)

Another way in which this is manifest is with repetitious sequences. Not to go into too much detail with this one, but most repetitious sequences are capable of making copies of themselves, either directly or indirectly, and inserting the new copy into the genome more or less at random. A very large percentage of our DNA, and that of most other mammals, consists of these repetitious sequences. In fact, you can contruct a phylogeny based upon them, and the tree you get is the same one that is based on morphology. (Something to think about: since these sequences insert more or less at random over time, how could humans and apes have most of the same ones in the same places if not by recent common descent?) As with introns, repetitious sequences are more common in "advanced" organisms, again presumably because faster replicators have much more selective pressure to remove them.

Now, back to your question, if the insertion/deletion occurs within an intron or a repitious sequence (and there is other "junk" too) then it will be very unlikely to have an effect on a protein coding ORF, and therefore, no effect on the organism. (And for you pendants out there, yes, it could occur in an origin of replication, a promoter sequence, the TATA box, etc. -- but these sequences are puny). And since as you can see that the DNA of most "big" organisms like ourselves contain only a small % of ORFs, then a single insertion/deletion event is unlikely to do anything at all. And even if it does, the effects might be minimal if it occurs in one of the last exons in a gene.

I'm sorry if I've confused you, but it's this sort of thing that you need to know in great detail if you ever want to make genetic arguments against evolution. In fact, the strongest evidence for evolution comes from this sort of knowledge. I have never heard a creationist even try to argue in terms that showed that he knew the first thing about molecular genetics; it's usually just some simplistic and ill-defined nonsense about "information".

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Old 01-17-2002, 05:23 PM   #27
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Correct me if I'm wrong, but I thought it went like this...
The yellow base is the one to be deleted.

Therefore radically altering all following information on that chromosome.

[Edit: The images are now broken, so I just removed them.]

[ January 19, 2002: Message edited by: CodeMason ]</p>
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Old 01-17-2002, 05:39 PM   #28
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CodeMason,

There are a couple of problems with your depiction. First off, I think that you've labeled your introns and exons backwards. Introns are the non-coding portions of a gene. Secondly, genes are expressed from any of the three reading frames. They aren't all in frame with eachother, just with their start codons. Even if a frameshift occurs within the protein-coding portion of a gene, other genes will still be in frame with their respective promoters.
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Old 01-17-2002, 05:55 PM   #29
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Yes, I did mixed up introns and exons, sorry.

So, are you saying, if have an intron sequence of CCA TGC, the gene would actually start in the middle because of the "ATG" in a certain frame?
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Old 01-17-2002, 06:13 PM   #30
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Basically, yes. The start codon defines the reading frame for that particular gene (or pseudogene depending on whether the appropriate promoter elements are in place).
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