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Author | Topic: Y.E.C. Model: Was there rapid evolution and speciation post flood? | |||||||||||||||||||||||||||||||||||||||||||||||
Taq Member Posts: 10044 Joined: Member Rating: 5.3 |
Faith writes: I can't call a mutation a mutation, I have to call it an allele, so I can't point out that mutations are usually neutral, second deleterious, so I can't dispute the argument that I have to account for alleles that Adam and Eve didn't have on the ground that they are just neutral mutations; No one is stopping you from saying that some alleles are detrimental, so I really don't understand what the problem is. If you want to plant your flag on the hill labeled "mutations don't happen", go for it. However, such a position is rather hard to defend being that we can directly observe mutations happening. Alleles is just another way of saying that mutations happen. If you don't object to the observation that mutations happen, then why object to the observation that mutations produce new alleles?
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Percy Member Posts: 22480 From: New Hampshire Joined: Member Rating: 4.8
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Putting my ignorance on full display, I found this paragraph particularly difficult:
quote: If I hadn't just looked it up earlier this morning I wouldn't remember what the MHC complex was - we've talked about several different genes, and to me they're still just alphabet soup. The terms polygeny and antigen are unfamiliar. I don't know what "class I" and "class II" molecules are. I think the sentence you emphasized contains the information Faith questions most:
quote: Faith doesn't accept that a high frequency means selection. She thinks all these alleles code for mostly the same proteins and so don't provide any additional benefit beyond the two she believes were contributed by Adam and Eve. She thinks it's just assumed that these alleles code for different proteins, not observed. Do you have any evidence that the alleles code for different proteins? One potential problem I see for the MHC example is that MHC is a complex of genes, not a single gene. When the article refers to "more than 200 alleles" it means across all the genes of the complex. How many genes is that? Looking this up in Wikipedia (Major histocompatibility complex) I see that its chromosome region contains 240 genes, half of which have "known immune functions." Half of 240 is 120, and since each gene has two alleles, one from each parent, that's 240 potential different alleles. Since Adam and Eve contributed two alleles for each of these 120 genes, that's more than enough to account for the "more than 200 alleles" that are currently observed. --Percy
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PaulK Member Posts: 17825 Joined: Member Rating: 2.2 |
quote: The question then is how does the frequency increase ? Faith resorts to - her word - flimflam - to try to cover up the frequencies but never honestly addresses the issue.
quote: No. It specifically states:
There are more than 200 alleles of some human MHC class I and class II genes, each allele being present at a relatively high frequency in the population. It pretty clearly refers to individual genes - "some genes" can hardly mean the whole of the complex. Edited by PaulK, : No reason given.
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Taq Member Posts: 10044 Joined: Member Rating: 5.3
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Percy writes: If I hadn't just looked it up earlier this morning I wouldn't remember what the MHC complex was - we've talked about several different genes, and to me they're still just alphabet soup. The terms polygeny and antigen are unfamiliar. I don't know what "class I" and "class II" molecules are. The Major Histocompatibility Complex (MHC) is a complex of over 200 separate genes. That is, there is a region in your genome made up of over 200 genes that produce all of your MHC proteins. Think of it like a car manufacturer that makes over 200 different models. These models can be grouped into about 3 main categories: cars, pickups, and SUV's. Those are like the 3 MHC groups, of which MHC I and MHC II have been studied the most. They are grouped into these classes due to the type of immunity they are involved in, be it bacterial pathogens (MHC II) or cancer (MHC I). The wide variety of MHC molecules allow them to bind to many different foreign and misformed proteins/molecules and present them on the outside of the immune cell. This allows T-cells to interact with the presented antigen and respond accordingly, either releasing cytokines to amp up the immune system to fight off infection or killing of a cell that is presenting the wrong proteins (cancer/tissue rejection).
When the article refers to "more than 200 alleles" it means across all the genes of the complex. That's not accurate. For any single gene in the complex there can be hundreds or even thousands of alleles. For example, one of the genes in the complex is HLA-DRB1. Again, that is just a single gene. For that single gene there are hundreds if not thousands of different alleles.
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Percy Member Posts: 22480 From: New Hampshire Joined: Member Rating: 4.8 |
PaulK writes: quote: No. It specifically states:
There are more than 200 alleles of some human MHC class I and class II genes, each allele being present at a relatively high frequency in the population. It pretty clearly refers to individual genes - "some genes" can hardly mean the whole of the complex. Good point, but can more consistent figures be nailed down? Taq just responded that some genes of the complex "have hundreds or even thousands of alleles" all by themselves. --Percy
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Percy Member Posts: 22480 From: New Hampshire Joined: Member Rating: 4.8 |
Taq writes: When the article refers to "more than 200 alleles" it means across all the genes of the complex. That's not accurate. For any single gene in the complex there can be hundreds or even thousands of alleles. For example, one of the genes in the complex is HLA-DRB1. Again, that is just a single gene. For that single gene there are hundreds if not thousands of different alleles. How do you reconcile "more than 200 alleles" across MHC I and MHC II with possibly "hundreds or even thousands" for a single gene? --Percy
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PaulK Member Posts: 17825 Joined: Member Rating: 2.2 |
"More than two hundred" is sufficient for "hundreds". The "thousands" could conceivably be more recent and accurate figures.
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Taq Member Posts: 10044 Joined: Member Rating: 5.3 |
Percy writes: Good point, but can more consistent figures be nailed down? Taq just responded that some genes of the complex "have hundreds or even thousands of alleles" all by themselves. The genomic region has been sequenced and you can find the map here: Complete sequence and gene map of a human major histocompatibility complex | Nature Excel spreadsheet containing all 224 genes here: http://www.nature.com/...01/n6756/extref/401921a0.table1.xls If you look at the function column you will notice that not all of the genes code for actual MHC proteins (i.e. antigen presenting proteins). There are a few chaperone and and protein modifying proteins in there, such as heat shock proteins and kinases. So not all of the genes in the MHC region are directly related to immunity. We can pick one of the MHC II molecules at random from the Excel list: HLA-DPB1. If you do a search for that molecule at Uniprot you get this page: UniProt If you scroll down to polymorphisms, it lists about 120 known alleles for the gene, at least by my quick count.
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Taq Member Posts: 10044 Joined: Member Rating: 5.3 |
Percy writes: How do you reconcile "more than 200 alleles" across MHC I and MHC II with possibly "hundreds or even thousands" for a single gene? Using our car manufacturing analogy from before, the MHC region is analogous to a single car manufacturer. Each gene in the region is a single vehicle model. Each vehicle model can have different trim packages, paint color, and so on. Each variant of the single type of vehicle is an allele in the analogy. There are 224 car models in the MHC region. Each car model can possibly have just a few different variants, but some are known for having hundreds to thousands of variants. Does this make sense? Edited by Taq, : No reason given.
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jar Member (Idle past 416 days) Posts: 34026 From: Texas!! Joined: |
Taq writes: Using our car manufacturing analogy from before, the MHC region is analogous to a single car manufacturer. Each gene in the region is a single vehicle model. Each vehicle model can have different trim packages, paint color, and so on. Each variant of the single type of vehicle is an allele in the analogy. There are 224 car models in the MHC region. Each car model can possibly have just a few different variants, but some are known for having hundreds to thousands of variants. Does this make sense? Following along with that analogy, some car models were sold fully equipped and with very few options. Other models from the same maker were marketed at the basic functionality level with a very long list of additional options that could be selected. In the latter case it was almost possible for each car sold to be unique.
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Taq Member Posts: 10044 Joined: Member Rating: 5.3 |
PaulK writes: "More than two hundred" is sufficient for "hundreds". The "thousands" could conceivably be more recent and accurate figures. The most up to date resource I could find is this one: HLA Nomenclature @ hla.alleles.org For HLA-DRB1 they have 2,058 alleles listed.
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Faith  Suspended Member (Idle past 1466 days) Posts: 35298 From: Nevada, USA Joined: |
Here's the quote that keeps being passed along from bluegenes' post on the MHC genes:
There are more than 200 alleles of some human MHC class I and class II genes, each allele being present at a relatively high frequency in the population. What I would like to know is what constitutes a "relatively high frequency in the population?" There are, what, about seven billion of us now? Say a single allele has 1000 variants (not a mere 200). I'm sure they wouldn't be evenly distributed in the population, but if they were neutral mutations one of the variants could be possessed by seven million* of us. Is that a high frequency? That would be the average frequency of the occurrence of a neutral mutation in the population if there were a thousand variants that were all neutral mutations. It would vary quite a bit having to do with where it first appeared so you should find higher frequencies in populations in that area, and of course drift. So, to repeat the question: What constitutes a "relatively high frequency in the population?" Edited by Faith, : No reason given. Edited by Faith, : No reason given. Edited by Faith, : No reason given. Edited by Faith, : No reason given. Edited by Faith, : No reason given. Edited by Faith, : No reason given. Edited by Faith, : No reason given.
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PaulK Member Posts: 17825 Joined: Member Rating: 2.2 |
quote: As I said earlier the frequency should tend to remain about the same for neutral drift. By chance some alleles will become more frequent but slowly. The absolute numbers would tend to track population change - starting when the mutation occurred. So even 1% would be quite surprisingly high - even allowing for multiple generations. You would need a very small population when the original mutation occurred for that to be the original frequency.
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Percy Member Posts: 22480 From: New Hampshire Joined: Member Rating: 4.8 |
I'll reply to your Message 248 and Message 249 in this single message.
Taq: Here's the image for reference:
About this from the comment beneath the figure:
quote: What is a haplotype? The Wikipedia article on Haplotype offers several definitions. What does the little symbol between curly braces mean?
quote: Does this mean that for some loci different people can have different genes instead of different alleles?
Excel spreadsheet containing all 224 genes here: http://www.nature.com/...01/n6756/extref/401921a0.table1.xls 96 of the 224 genes are actually pseudogenes, which Wikipedia defines as disabled or only partially functioning.
We can pick one of the MHC II molecules at random from the Excel list: HLA-DPB1. If you do a search for that molecule at Uniprot you get this page: UniProt If you scroll down to polymorphisms, it lists about 120 known alleles for the gene, at least by my quick count. Here's the list of alleles:
quote: There are 118 (good "quick count" by you). Faith is asking how we know which alleles produce unique proteins that do something different. --Percy
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bluegenes Member (Idle past 2499 days) Posts: 3119 From: U.K. Joined: |
Percy writes: Putting my ignorance on full display, I found this paragraph particularly difficult:
quote: Translation: Because there are several genes that produce different molecules that detect, bind to, and "present" foreign bodies (to killer T-cells or other killers which get rid of them) in both classes (the difference in the classes doesn't matter for our discussion), at least 6 or 7 different such molecules will be expressed in the cells of all people. In fact, the number (of different foreign body detecting + presenting molecules) expressed in the cells of most people is greater because of the very large amount of different alleles (coding sequences) on most of these genes (meaning the two copies of each gene per. individual are very likely to be different =heterozygosity) and the fact that all alleles are codominant (the products of both are expressed - neither is recessive). Better? Or worse? The variance in alleles on the same genes is advantageous (it increases the range of foreign bodies that can be detected), so variance itself is under positive selection.
Percy writes: If I hadn't just looked it up earlier this morning I wouldn't remember what the MHC complex was - we've talked about several different genes, and to me they're still just alphabet soup. The terms polygeny and antigen are unfamiliar. I don't know what "class I" and "class II" molecules are. There are several genes (polygeny) that produce the proteins that detect and present "poisonous" foreign bodies (antigens) to anti-bodies. (Forget classes for now).
Percy writes: I think the sentence you emphasized contains the information Faith questions most:
quote: Faith doesn't accept that a high frequency means selection. She thinks all these alleles code for mostly the same proteins and so don't provide any additional benefit beyond the two she believes were contributed by Adam and Eve. She thinks it's just assumed that these alleles code for different proteins, not observed. Do you have any evidence that the alleles code for different proteins? Yes. It does actually state that indirectly in the second sentence of the bit you quoted above.
quote: I quoted another extract from the same paper (actually, a book) in Message 189quote: Don't worry about things like the disgusting sounding "endoplasmic reticulum", but I hope you get the gist. The "T cells" are pathogen killers which act on signals from these varying alleles. It's the famous "evolutionary arms race" that's being described.
Percy writes: One potential problem I see for the MHC example is that MHC is a complex of genes, not a single gene. When the article refers to "more than 200 alleles" it means across all the genes of the complex. No. It means more than 200 on some individual genes.
Percy writes: How many genes is that? Looking this up in Wikipedia (Major histocompatibility complex) I see that its chromosome region contains 240 genes, half of which have "known immune functions." Half of 240 is 120, and since each gene has two alleles, one from each parent, that's 240 potential different alleles. Since Adam and Eve contributed two alleles for each of these 120 genes, that's more than enough to account for the "more than 200 alleles" that are currently observed. No. There are more than 200 on some individual genes. Adam and Eve: maximum possible 4. Drift on neutral alleles might give anything from 0 to 4 more in a sample of 100 individuals on any given gene (modern individuals would differ from A&E on about 1% of all coding loci) giving a likely maximum of 8 (average 5 if A&E had 4). These would typically differ by a single point mutation from A&E originals. The sample of 120 Cubans I posted earlier had 19 different alleles on HLA -A (one gene). So, are you beginning to understand why I'm saying that the YECs need to include mutation and positive selection into their model?
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