Y.E.C. Model: Was there rapid evolution and speciation post flood?

NosyNed is trying to accommodate your objection to the definition to "allele", but I believe it will just cause confusion. "Allele" has a definition and you can't change it. An allele is any unique nucleotide sequence for a gene. Some alleles produce different proteins and functions, some don't, but they're all alleles. Just to emphasize the point, this is an incorrect definition of allele. An allele is any unique nucleotide sequence at a gene locus. It does not need to code for a different protein to be a different allele. When a mutation causes a new and unique nucleotide sequence then it is a new allele, whether it codes for a new protein or not.The nucleotide sequence of an allele is divided into nucleotide triplets called codons. Each 3-nucleotide codon codes for an amino acid that will be added in sequence to the protein as it is constructed. This table from Wikipedia shows which codons create which amino acids (it's big and very legible if you expand it): Since you've said it one more time I want to emphasize one more time that this is incorrect. A different nucleotide sequence is a different allele, whether it produces a different protein or not. Because most of the genome is non-coding, most mutations occur in non-coding regions and are therefore neutral. But mutations that occur in coding regions are *not* "predominantly neutral." As you can see in the chart above, most single nucleotide mutations will result in different amino acids and therefore different proteins.--Percy

I tried to read this paper but found it outside my pay grade. It might help if you could boil the paper down into something less technically dense. I don't think this diagram will be understood without some provided background about what "peptide antigen binding" is and so forth. I kind of get it because I slogged through the first quarter or so of that paper, but I could do with some clarification, too.--Percy

Putting my ignorance on full display, I found this paragraph particularly difficult:

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Because of the polygeny of the MHC, every person will express at least three different antigen-presenting MHC class I molecules and three (or sometimes four) MHC class II molecules on his or her cells. In fact, the number of different MHC molecules expressed on the cells of most people is greater because of the extreme polymorphism of the MHC and the codominant expression of MHC gene products.

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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:

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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.

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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

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

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

I'll reply to your Message 248 and Message 249 in this single message.

Taq:

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The genomic region has been sequenced and you can find the map here:

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Complete sequence and gene map of a human major histocompatibility complex | Nature

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Here's the image for reference: About this from the comment beneath the figure:

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As will be the case for the rest of the human genome, the MHC reference sequence is a composite of different haplotypes.

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What is a haplotype? The Wikipedia article on Haplotype offers several definitions.What does the little symbol between curly braces mean?

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However, in regions with known differences in gene content...

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Does this mean that for some loci different people can have different genes instead of different alleles? 96 of the 224 genes are actually pseudogenes, which Wikipedia defines as disabled or only partially functioning. Here's the list of alleles:

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Polymorphismⁱ
The following alleles of HLA-DPB1 are known: DPB1*01:01, DPB1*01:02, DPB1*02:01, DPB1*02:02, DPB1*02:03, DPB1*03:01, DPB1*03:02, DPB1*04:01, DPB1*04:02, DPB1*04:03, DPB1*05:01, DPB1*05:02, DPB1*06:01, DPB1*06:02, DPB1*08:01, DPB1*08:02, DPB1*09:01, DPB1*09:02, DPB1*10:01, DPB1*10:02, DPB1*11:01, DPB1*11:02, DPB1*13:01, DPB1*13:02, DPB1*14:01, DPB1*14:02, DPB1*15:01, DPB1*15:02, DPB1*16:01, DPB1*16:02, DPB1*17:01, DPB1*17:02, DPB1*18:01, DPB1*18:02, DPB1*19:01, DPB1*19:02, DPB1*20:01, DPB1*20:02, DPB1*21:01, DPB1*21:02, DPB1*22:01, DPB1*22:02, DPB1*23:01, DPB1*24:01, DPB1*24:02, DPB1*25:01, DPB1*25:02, DPB1*26:01, DPB1*26:02, DPB1*27:01, DPB1*28:01, DPB1*29:01, DPB1*30:01, DPB1*31:01, DPB1*32:01, DPB1*33:01, DPB1*34:01, DPB1*35:01, DPB1*36:01, DPB1*37:01, DPB1*38:01, DPB1*39:01, DPB1*40:01, DPB1*41:01, DPB1*44:01, DPB1*45:01, DPB1*46:01, DPB1*47:01, DPB1*48:01, DPB1*49:01, DPB1*50:01, DPB1*51:01, DPB1*52:01, DPB1*53:01, DPB1*54:01, DPB1*55:01, DPB1*56:01, DPB1*57:01, DPB1*58:01, DPB1*59:01, DPB1*60:01, DPB1*62:01, DPB1*63:01, DPB1*65:01, DPB1*66:01, DPB1*67:01, DPB1*68:01, DPB1*69:01, DPB1*70:01, DPB1*71:01, DPB1*72:01, DPB1*73:01, DPB1*74:01, DPB1*75:01, DPB1*76:01, DPB1*77:01, DPB1*78:01, DPB1*79:01, DPB1*80:01, DPB1*81:01, DPB1*82:01, DPB1*83:01, DPB1*84:01, DPB1*85:01, DPB1*86:01, DPB1*87:01, DPB1*88:01, DPB1*89:01, DPB1*90:01, DPB1*91:01, DPB1*92:01, DPB1*93:01, DPB1*94:01, DPB1*95:01, DPB1*96:01, DPB1*97:01, DPB1*98:01 and DPB1*99:01. The sequence shown is that of DPB1*04:01.

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There are 118 (good "quick count" by you).Faith is asking how we know which alleles produce unique proteins that do something different.--Percy

I'm still trying to decode this paragraph from the book:

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Because of the polygeny of the MHC, every person will express at least three different antigen-presenting MHC class I molecules and three (or sometimes four) MHC class II molecules on his or her cells. In fact, the number of different MHC molecules expressed on the cells of most people is greater because of the extreme polymorphism of the MHC and the codominant expression of MHC gene products.

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Just for reference, here's the diagram listing all the genes of the MHC complex: Let's break that paragraph down. First it says, "every person will express at least three different antigen-presenting MHC class I molecules." If there are over a hundred class I MHC genes, why do people express only "three different antigen-presenting MHC class I molecules"? Shouldn't most people be expressing many, many different molecules, sometimes as many as 200, depending upon the degree of heterozygosity.Then it says, "three (or sometimes four) MHC class II molecules." If there are around 60 class II MYC genes, why do people express only "three (or sometimes four)" MHC class II molecules. Shouldn't most people be expressing many, many different molecules, sometimes as many as 120, depending the degree of heterozygosity.Then after giving these very precise numbers of "three (or sometimes four)" it continues on to contradict itself and say "the number of different MHC molecules expressed on the cells of most people is greater." So who knows what to think?Now before you reply let me quote some of what you say about this paragraph: So you agree that it's more than "three (or sometimes four)", and the paragraph concludes by stating that it's more, but then why did they ever give figures like "three (or sometimes four)". And am I right in stating that it should be much, much more than this paragraph states or implies?This quote from the book is an important piece of the information Faith is looking for:

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Most polymorphic genes encode proteins that vary by only one or a few amino acids, whereas the different allelic variants of MHC proteins differ by up to 20 amino acids. The extensive polymorphism of the MHC proteins has almost certainly evolved to outflank the evasive strategies of pathogens.

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So it is a fact that the MHC complex has over a couple hundred genes that taken together have thousands of different alleles that produce very different proteins. The question Faith has to address is how this happened in just six thousand years starting with a maximum of four alleles per gene in the population (I know Faith is claiming there were only two alleles per gene, but she's never supported this statement). Yes, I understand, but I'm looking for the data that proves this view. Faith now has to accept that the MHC complex has hundreds even thousands of unique alleles that produce unique proteins, but she still doesn't have the frequency data, and she doesn't understand why that data indicate that it would have taken much more than six thousand years.--Percy

God would have had to change the X chromosome to a Y, so we know he made at least some genetic changes when he made Eve. It doesn't seem possible to know from just the Bible what specific genetic changes God made, so that seems to argue that the possibility of a maximum of 4 alleles per gene has to be considered, not ruled off the table.--Percy

The two strands are mirror images of each other. A always pairs with T, and C always pairs with G. When DNA replicates by splitting the two strands, that's how identical copies form.AbE: I see this question has already been answered in better detail - apologies.One question I've sometimes wondered about, and maybe someone here has an answer, is how geneticists decide which half of the paired DNA strands to list. For example, if they provide this short DNA sequence: They could just as easily have provided the sequence of the other strand: Which to choose?--PercyEdited by Percy, : AbE.

I guess I must have misunderstood what an "antigen presenting molecule" is. I was assuming from context that it was a synonym for a protein coded for by one of the MHC genes. Now that I know that is wrong, let me try again. Looking this up at Wikipedia I found "antigen presenting cell," but not "antigen presenting molecule." Wikipedia says that an "antigen presenting cell" is one that...well, never mind, this is getting complicated, and I'm not even sure I'm on the right track. Can you boil this down for me? If only 3 class I genes are involved, and only 3 (sometimes 4) class II genes, then now I'm confused why Taq gave me a diagram and an Excel list of all the MHC genes.But anyway, if we're only talking about 6 or 7 genes then it would be helpful to know the names of the genes, the number of alleles for each one in the population, and how we know that the alleles produce unique proteins. Okay, that gives us as many as 14 "antigen presenting molecules" for a single individual.--Percy

Before replying I want to first thank everyone trying to explain this to me, even if I didn't reply to each message. We're arguing to Faith that there are more alleles that produce functionally different proteins with significant frequencies in the population than could have arisen since Adam and Eve, and I've been inquiring about the data that proves this point, but if I've gone off track in one area maybe I've gone off track in others, too. Am I right about the point we're trying to make to Faith? If so, has the data I'm looking for been presented? If so, could someone point me to it?--Percy

My understanding is that Faith accepts this argument. She believes that Adam and Eve together contributed at most two alleles for each gene, and that any gene today that has more than two alleles has experienced mutations, but she believes the alleles neutral, performing the same functions as the original two alleles.Efforts have been to persuade Faith of two things:

• That the frequency of the alleles indicates strong selection and therefore different function. Faith rejects this argument, arguing that if the alleles did the same thing as existing alleles then they would also have strong selection.
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• That there has not been enough time since Adam and Eve to create the distribution of alleles we observe in the human population.

I'm seeking the evidence that proves these two points. It may have been presented already, but not in a form I understand.This might have been mentioned already, but this was new to me: the MHC complex and the HLA complex are the same thing.--Percy

Don't you mean that the peptides bound to the proteins produced by the alleles? I tried to read the paper you referenced in Message 270 (HLA Class I Alleles Are Associated with Peptide-Binding Repertoires of Different Size, Affinity, and Immunogenicity) and found it impenetrable. Right. Explaining again, in Faith's view Adam and Eve contributed at most two alleles for each gene, and since creation any new alleles must be neutral and not perform any new function. But since the analysis in the paper reveals many more than two differently functional alleles for each gene, Faith must be wrong.The problem is that I can't understand the paper well enough to see how it supports this point.--Percy

I'm gradually picking up some terminology. Is it correct to say the MHC complex of proteins is produced by the HLA complex of genes? Asking the same question I asked Taq, why do you say that the alleles bind to peptides, instead of that proteins produced by the alleles bind to the peptides? And what we need is evidence that many more that two alleles of the same gene have different functions in that they bind to different pathogen peptides. When you say "floating around" I think you mean "floating around in the population?" If so, then for contagious pathogens this could be deemed a form of what is called herd immunity? As I mentioned to Taq, I found the paper impenetrable. I didn't find this paper any easier to digest. Quoting from your Message 271: I don't know the definitions for "repertoire" and "supertype". It isn't just the definitions but the context. I don't mean to appear helpless, but I have limited free time for figuring all this out on my own.--Percy

What's actually pretty clear is that evidence has been presented that we don't understand. Taq and Bluegenes suggested these two papers:

• HLA Class I Alleles Are Associated with Peptide-Binding Repertoires of Different Size, Affinity, and Immunogenicity
  
• Functional classification of class II human leukocyte antigen (HLA) molecules reveals seven different supertypes and a surprising degree of repertoire sharing across supertypes

Once we understand the relevant portions of these papers we can judge the evidence. Or perhaps more easily understood evidence will be presented.--Percy