Molecular Population Genetics and Diversity through Mutation

Well this is interesting...Good alleles are part of the original created genome and bad alleles are due to mutation, so now you only need to account for good alleles. Well that certainly solves your problem of having to explain multiple alleles - just declare the additional alleles as 'bad' and then they don't count. Heck, you don't even have to know anything about what the alleles actually do because you know that if the allele came about due to mutation it is automatically bad.HBD

So you didn't bother to learn anything about the Runx-2 genes I brought up in Message 275? Runx-2 variants are not defective, they are different. They affect the length of the snout. Is there a "perfect" form for the length of the snout? No, there is variation. Variation is not "bad." The one who is being deceptive is you, Faith. You read a paragraph on Wikipedia about polymorphic alleles and it gives an example of a polymorphic locus that includes a disease allele and you extrapolate that to ALL polymorphic alleles. You are just looking for a reason to dismiss the study I presented and not have to address polymorphic loci. I did not present a study that looked at diseased alleles and the study was about dogs not bacteria or other "icky" organisms.Disease alleles are easy to identify since they produce a distinct phenotype. They also generate a lot of attention since lots of money goes into funding research into diseases. They don't represent ALL alleles out there.Which alleles in the Runx-2 series are the defective alleles and which are the original alleles?Which alleles in the Human ABO gene are the defective alleles and which are the original alleles?You have no way of knowing, but I bet you know for sure that several of them are indeed defective. You won't have phenotypic diversity without genetic diversity. So if there is phenotypic diversity that is a sure clue that there is also genetic diversity. Of course you know this, so I am not sure why you can't grasp the point. I am certainly not the one who has a hard time grasping genetics, Faith. But you are probably right that this discussion is hopeless. You are just incapable of defending your premise with any thing other than denial, obstinance and conjecture. The only argument you actually have is that you KNOW you are right and that evolution is wrong.HBDEdited by herebedragons, : No reason given.

The reality is that your argument is not very well detailed, it is pretty much a vague set of generalizations about a limited range of topics that broadly cover evolution. Little wonder that we "straw man" your arguments. Besides, your complaints about "straw men" is designed to simply avoid having to address the rebuttals. I mean it would be a different thing if you weren't creating caricatures of your own and of the processes you discuss; such as: That is not what the article says. That is your spin on it based on your own person bias. This is disingenuous and even dishonest. There are alleles that cause disease. There are alleles that make on organism less fit in a particular environment. There are alleles that make an organism more fit in a particular environment. There are alleles that have little to no effect on the organism, but are just different. There are alleles that cause morphological changes but that don't really affect fitness much. We have not been deceptive about these facts. Just because you have been trying to define 'allele' in a way that supports your premise is not the fault of any of us. In fact, I have pointed out to you on several occasions that your idea of what alleles are is misinformed.Alleles are different variants of a gene at a specific locus. This is the definition you will find just about everywhere. From that definition it should be abundantly clear that a disease allele is, in fact, an allele.Now, describe which of the Runx-2 alleles is a disease allele; and which of the human ABO gene alleles are disease alleles. Both are polymorphic genes and neither are defined as "disease-causers" as you claim.HBD

If by "stranglehold" you mean that we understand that disease alleles are... alleles, since they actually are alleles. If you are trying to say that we think that "disease alleles" increase diversity and lead to evolutionary progress, well then, that is YOUR strawman representation of what we have been saying.Again, the example I gave you of Runx-2 has no "disease alleles" and you couldn't point to one of them that was... or did you?? LOL. That doesn't address my question at all. Do you know what that reference is for?First of all, it is for a mouse gene, not for a dog gene. This would be an example of a homolog, not a dog allele. I presented a paper on dog alleles.Second, it is a knockout mouse line. (Jargon: knockout means a genetic modification that deletes or otherwise inactivates a specific gene). This is not a natural mutation but a research tool.From the "Mutation description" section:

quote:

---

Allele Type:Targeted (Null/knockout)

​

Mutations: Insertion, Intragenic deletion

​

Mutation details: The P1 promoter and exon 1 were replaced with a neo cassette via homologous recombination. This specifically deleted the Runx2-II isoform and not the Runx2-I isoform. Rt-PCR confirmed the absence of Runx2-II RNA and the presence of Runx2-I RNA.

---

So... my question was NOT is there any kind of mutation that could occur in the gene that would cause disease, it was which of the dog alleles was diseased?HBD

Indeed it probably does regulate the same developmental pathway. BUT... we were not talking about mouse alleles, we were talking about dog alleles. Perhaps you lost track of the line of discussion, which would be understandable... Here is the basic outline of how I remember the discussion going:Faith: claimed that mutation can't add genetic diversity and if it did, it would mess up the breed.HBD: submitted an article describing the Runx-2 gene which has added diversity to the dog "kind" AND has not messed up the breed. In fact, breeders began selecting for the new alleles which changed the look of the breed over the yearsFaith: read an article on Wikipedia that she interpreted as saying ALL polymorphic alleles were disease allelesHBD: asked which of the dog alleles presented in the paper were "disease alleles"Faith: replied with an example of a genetically engineered mouse line where a portion of the Runx-2 gene was knocked out as evidence that all mutations cause "disease alleles":blink:You don't think mice and dogs are in the same kind do you? So why would you present mouse alleles as evidence in a discussion about diversity of dogs? Yes, Runx-2 is involved in the development of canio-facial features. Again, it is a transcription factor (Jargon: a transcription factor is a protein that binds to specific DNA sequences and regulates transcription)(Jargon: transcription is the conversion of DNA to messenger RNA - mRNA) and the mutations described in the paper affect the protein's binding affinity to it's target sequence and thus affects transcription rates. "That gene" is not presented as creating abnormalities, the specific mutation that the researchers put into the gene caused those abnormalities. They deleted an exon, the protein was severely damaged, possibly non-functional - it is called a "knockout mouse" (already explained this jargon term). Researchers uses this technology all the time, it helps identify the function of particular genes and how they interact with other genes.The dog alleles do NOT have the same mutation - not all mutations are created equal. The dog variations are in the microsatellites, the tandem repeats. The number and ratio of repeats varies and affects binding affinity and therefore transcription rates. There probably is a connection. If you look at the bulldog skull, it seems clear that the changes are related to the bulldogs breathing problems. Breeders selected for those traits, didn't they. Thus why breeding is referred to as ARTIFICIAL SELECTION. Traits that in the wild would be detrimental actually give the individuals greater reproductive success - which would mean that the traits in question, despite their seemingly harmful effects, have improved fitness - that is, individuals are selected FOR those traits.The conversation about "what is disease?" actually comes up quite frequently. While it seems as if it should be a straight-forward, easy definition, it turns out to be a bit elusive at times. For example, there is a fungus called Ustilago maydis that causes a "disease" called corn smut. pretty gross, huh? So it would clearly be a disease right? Well it turns out that this corn smut is also a delicacy in some parts. So... is it a disease or a delicacy? I guess it depends on who you ask. If you ask a farmer who is trying to sell corn, it is a disease. If you ask a corn smut canner, it is a delicacy.Same way with the bulldog. I have a friend who has bulldogs and she just loves them, thinks they are so cute. They drove like 200 miles to buy their dogs and paid like $1000 for them. They like the flattened nose. I bet you won't get them to say that their breed is "diseased" or malformed. It is exactly what they want in a breed.So your use of the word "normal" in this context is rather odd. What is "normal?" I guess you should say that only the original "kind" was normal and all other sub-species, breeds, or whatever are degraded somehow. But most people don't see it that way.So bottom line... different is not defective. Genetic diversity has increased in dogs. Humans selected traits they found appealing. Faith doesn't get to define normal when it comes to nature.HBD

Yea, I guess to you everything is sick and diseased. Perhaps breeding programs aren't as good of an analogy to natural systems as you thought they were? No, it's the complexity of the interactions in nature. It's that nature doesn't fit into a nice neat mold that you have envisioned that it should fit into. Wrong. This is your strawman characteriztion One of my favorite professors had a saying: "Biology is the study of plants and their parasites." Think about it Faith, we are all parasites. This is simply not true. Especially in artificial selection systems. Runx-2 is a gene locus. Variations in the sequences at the gene locus are called alleles. These alleles are formed when the sequence of that gene locus changes and is passed on to the offspring. These changes are called mutations. Runx-2 in mice is at a different gene locus. Dogs and mice do not have the same genome. The knockout mouse is used for experimental purposes. This makes no sense. What is the evidence that mutations commonly kill alleles? What does "kill the allele" even mean? Uhmmm... I don't think you understand how genes code for products and what those products do after they have been produced. If you did, I can't imagine why you would say something like this. AlbinismHBD

Right, mutations provided the variability and the breeders determined what variants were desirable. If you remember the picture of the dog skulls I posted a while back the bull terrier is in the middle (B) from 1931 (Top), 1950 (Middle), and 1976 (Bottom).It shows that the changes occurred over a period of 45 years and were incremental. This is important because it shows this wasn't due to a single, large scale mutation but a series of shifts in expression. Another thing that I didn't want to bring up with Faith (but I think you can handle it ) is that often times a undesirable trait will hitchhike along with a desirable trait due to linkage (Jargon: linkage means that genes are located very close to one another on a chromosome and are inherited together) and then end up fixed in the breed. Sometimes these inherited disorders can be bred out by crossbreeding and then backcrossing until the normal allele is fixed in the breed.

quote:

---

Purebred Dalmatian dogs are all homozygous for a mutation in SLC2A9, a gene that encodes a membrane protein involved in uric acid transport [77]. This mutation appears to be closely linked to a locus controlling coloured spot size in the Dalmatian coat and probably rose to high frequency during selection for a distinctive spotting pattern in achieving breed standard. Because of this mutation, Dalmatians are susceptible to hyperuricosuria and formation of urinary calculi that can obstruct the urinary tract (a life threating complication) and which may require surgical removal.

​

To correct this problem, a Dalmatian was outcrossed with a Pointer homozygous for a functional allele at SLC2A9 and then successive backcrosses to the Dalmatian line were performed [78]. As shown in Figure S1 of Bannasch et al. [78], this resulted in dogs that were heterozygous for the mutation (and therefore excreted only low levels of uric acid) but of predominantly Dalmatian genetic background. The backcross dogs descended from the original Dalmatian x Pointer cross have been registered with the American Kennel Club in the United States and meet the breed standard. As seen in Figure 3, after five generations of backcrossing to the original breed, the genetic contribution is 96.9% from this breed while by ten generations it is 99.9%.

---

The challenges of pedigree dog health: approaches to combating inherited diseaseHBDEdited by herebedragons, : No reason given.

Or... you now have a population of plants with pink flowers AND a population of plants with white flowers AND a population with large white flowers with a blue center. So you may have lost the pink allele in the white-flowered version, but that doesn't mean the pink allele is lost completely. And if they won't cross breed, you now have three separate species that originated from a common ancestor by descent with modification. Well, if ALL Chihuahuas bred with cocker spaniels, then yes, the Chihuahua breed would no longer exist. But what if only the Chihuahuas in Southern California were bred with cocker spaniels but the Chihuahuas in the rest of the world were not bred with cocker spaniels, the breed would not be lost. But there are still wild pigeons, right? And why do you consider losing the "wild" traits to be a "cost?" The point is that the traits in the new pigeon "species" were favored for some reason and so they were selected for. Yes, you have lost some traits in your new pigeon breed, but now you have a pigeon that is "better" than the wild breed.While it may be true that diversity has decreased from the wild type to the new breed, there is no reason that variation can't increase in the new breed due to new mutations. Of course if those mutations are undesirable, they will be unlikely to make it into the next generations. However, if they are neutral or of minimal effect they can continue to accumulate until the next selection event, where a desirable trait emerges (such as a blue center in a flower, a flatter, shorter snout in a bulldog, or a peculiar color in the pigeon feathers), and now there will be the wild-type, the first breed and a new breed.Honestly, this is beginning to sound like a slightly more sophisticated version of the "If humans evolved from monkeys then why are there still monkeys?" argument coupled with the no new genetic information argument.HBD

The problem is you seem utterly incapable of considering how your argument fits within the bigger picture. I am not "misrepresenting" your argument, I am considering it in within the larger context, which needs to be done in order for your argument to gain any validity. If that was your WHOLE argument, that would be one thing, but it's not is it? Your whole argument is that the ToE is not a workable theory because speciation requires a reduction in genetic diversity. In response to this, it is completely appropriate to point out that in the big picture, this does not appear to be the case. I pretty much agree with you on the point that speciation results in a reduction in genetic diversity (although I would take issue with saying it MUST result in a reduction, but I will come back to that in a minute). However, you are missing the point that between speciation events (that result in a reduction in genetic diversity) there is a subsequent increase in genetic diversity through several mechanisms.You keep saying this proposed increase would only serve to "ruin" the breed, but isn't that what speciation is; the changing of a population so that they are no longer recognized as the original population? But then you refer to that as "ruined." It seems perfectly acceptable to point out that Chihuahuas are not "ruined" when a subgroup experiences mutations; nor fancy breed pigeons "ruined", nor wild pigeons, nor populations of plants with pink flowers. But I have shown you examples of mutations that mutations that altered breeds in DESIRABLE ways; that is, the breeders found those traits favorable and then selected for them. Which is admitting that genetic diversity can increase between selection events. It is difficult to imagine why you consider a mutation a liability to the breed when it can create a trait that can be selected at a later time. IF the mutation creates an undesirable trait, then yes, it would be a liability and breeders wouldn't use that individual to bred their next generation. Since you say this is the MAIN point, let's consider it directly.1) Consider a population that splits into two identical subpopulations. Each subpopulation (we will call them 'Sub1' and 'Sub2') has identical genetic diversity. 'Sub1' has a mutation in gene 'A' and that mutation is selected for so that one of the original alleles are lost. The population has not had a net loss of genetic diversity since it gained 1 allele and lost 1 allele. 'Sub2' also experiences a mutation but in gene 'B'. It is also selected for by eliminating one of the original alleles. Again, no net loss in genetic diversity. 'Sub1' then has another mutation in a different gene, gene 'C' which is then selected for by eliminating the other allele at that locus. 'Sub2' has a neutral mutation in gene 'D', so other alleles at that locus are not eliminated, so there is a net increase in genetic diversity.The important thing to consider here is that there are now 4 genetic differences between the two subpopulations. If one of those genetic differences causes the two subpopulations to be unable to reproduce, they are then considered separate species - no loss of genetic diversity.This is essentially the scenario Dr. A presented in his graphical sketch in Message 429, and while sure this situation is hypothetical, it at least shows that speciation is theoretically possible without a net loss of genetic diversity.2) Polyploidy is common among plants (some estimates are that up to 80% of all angiosperms are polyploides) and even occurs in animals, although not nearly as commonly. Polyploidy is when the chromosomes fail to segregate properly during meiosis and it results in an increase in the number of chromosomes in the offspring. So while the typical chromosomal situation is diploid (2n), polyploidy results in triploids (3n), tetraploids (4n), hexaploids (6n), octaploids (8n) and even higher numbers. These polyploidy events can result in rapid speciation. Example: Mimulus peregrinus.The cool thing about whole genome duplication is that it provides the organism with two copies of every gene. This means that one of the copies of a gene can accumulate mutations and its function can diverge without having a detrimental effect on the organism since there is at least one functioning gene at all times. I don't know how you could consider whole genome duplication to be a reduction in genetic diversity.3) Horizontal gene transfer (HGT) appears to be fairly common. An example is the sweet potato. Agrobacterium is a genus of bacteria that is capable of injecting genetic material into a host and this genetic material can become incorporated into the host's genome and passed on to the progeny. Agrobacterium uses a piece of transfer DNA (T-DNA) to relocate genetic material into the host. This T-DNA sequence was found in the sweet potato genome. They found the T-DNA insert in every sweet potato variety tested and in none of the wild relatives. In addition, this inserted piece of DNA from Agrobacterium was being expressed! This suggests that the transferred gene(s) contributed to a trait that was selected for early in the domestication of the sweet potato.I don't know how you could consider HGT to be a reduction in genetic diversity.So here are presented 3 reasons why speciation does not REQUIRE a loss in genetic diversity. So while it is correct that selection of new phenotypes will generally result in a loss in diversity, it is not a requirement for divergence (ie. speciation). And the suggestion that the ToE is a failed theory because of that point ignores the processes that increase or maintain genetic diversity. As a final point, your use of the words 'species', 'breed', 'variety', etc. are inconsistent and confusing. Here you seem to be using 'species' as indicating 'kind', as if all populations arising from the original pair are all the same 'species' or 'kind' and differentiated populations are then subspecies. Do you consider all descendants of the original ark pair to be the same species? This type of usage is terribly confusing since those words already have clear meanings. You should stick to using the accepted meanings for those words.HBD