Questions on "Random" Mutations

Imagine your whole life run in reverse.1) You as you are now; an adult human being composed of billions of cells that, individually, contain your entire genome. As your cells age and are exposed to elements in your environment that damage DNA (which we call mutagens), some cells accrue changes to that copy of your genome that makes them different from other cells. Some of these differences can cause diseases like cancer. Some cells become so damaged that your body sends them a chemical "self-destruct" signal, and they die. As your cells die, they are replaced by new cells formed from old ones by mitosis.2) All your body's cells - including the gametes produced by your genitals - are descended through mitosis from the original single cell that, at one point, implanted itself in your mother's uterus and began to gestate.3) That cell is the result of a fusion of two cells, one donated by each of your parents. Each cell contributes one half each of 23 pairs of homologous chromosomes. The 23rd chromosome donated by your father determined your sex. The cell donated by your mother contributes a small city of cellular organelles, including mitochondria, which have their own "private" genetics.4) While the physical organs that produce gametes differ between the sexes, the process of gamete formation is similar. A special kind of stem cell undergoes mitosis, then undergoes a special form of cell division where half of the chromosomes go one way and the other half go the other way. (This is called meiosis.) These produce gametes with one each of 23 pairs of your parent's chromosomes, assorted randomly.For your mother, this process occurred about 500 times in her embryonic ovaries, before she was even born. For your father, this process happened roughly 1.5 million times every day.5) and so on for your parents, and their parents, etc.The long and the short of this is that there's really two different kinds of mutations. The mutations that happen during Part 4 are passed onto you if that's one of the cells that combines to form you, and then they're replicated into every cell in your body, including the gametes that you produce (and thus, stand a chance of being passed on to your offspring.) We call these germline mutations.Mutations that accrue after your fertilization, when your zygotic self began to produce the rest of your body's cells through mitosis, aren't shared by your entire body. Mutations that happen when you're an adult (usually somewhere near the surface of your skin, as a result of radiation) are limited to that cell, typically. Since your gametes don't share the same mutation, you can't pass these mutations on to your offspring. We call these somatic mutations.Mutations can occur in your gamete-producing cells. Like somatic mutations they're not shared by the rest of your cells but they can be passed on to your offspring. These are somatic mutations to you and germline mutations to your offspring.Since your germline mutations are shared by all your body's cells, these mutations can result in characteristics we can observe at the macro level. For instance, a mutation that prevents your body from producing a certain kind of pigment results in albinism.Somatic mutations typically don't result in macro-observable changes, but occasionally they cause localized problems, like tumors.I guess the take-home message here is that, in the same way you have a family tree, your body's cells have their own family tree; and like the way all species have a single common ancestor, your body's cells have a single common ancestor, as well.

In humans, embryo stage is considered to begin around the zygote implants in the uterine lining, at which point the original zygotic cell has undergone enough cell division to form an inner and outer cell mass; the inner mass develops into the embryo and the outer mass forms such auxiliary structures as the placenta. Differentiation. Cells in the body perform a wide variety of different functions, depending on how they've differentiated. But ultimately all the body's cells are daughters of a "stock" of relatively-undifferentiated cells called "stem" cells.If you imagine a "family tree of cells", these progenitor cells are the root, or the stem, hence the name. Indeed. It's even less likely than your scenario would indicate, because there's a "crossing-over" effect that sometimes happens in meiosis that I omitted. The long and the short of it is that homologous chromosomes occasionally exchange sequences, and that produces even further genetic variation in offspring. About that, yes. (As is usually the case with biology the "real" story is a little more complicated than the simple models we talk about, but let's save that for later.) If you consider the X/Y chromosomes, you can see this principle in action - half of your offspring should get your Y chromosome and be male, and half should get your X chromosome and be female. (The mother, of course, always passes on one of her two X chromosomes.) And it's well-known that the human race breaks down roughly half male and half female. If we were to add up all the mutations present in your current adult body, from every cell, we would indeed find that you have a lot more somatic mutations than germline mutations, but that's not because your gametes have less genes; it's because your body has a lot less gametes than somatic cells.If you can imagine an ultraviolet ray from the sun heading towards you, it could theoretically shoot right through the nucleus of any one of your body's cells, but most likely, it's going to hit the nucleus of a cell in your skin - because that's what's closest to the sun, obviously. That ray makes a chemical change to your DNA that may or may not be repaired.The odds that its going to hit a cell in your testes is fairly low, and the odds that the cell in your testes is a sperm cell is even lower.But not non-zero. And the result could be a genetic change that you pass on to your offspring. Consider how many ultraviolet photons are streaming out of the sun per second, and you start to get an idea of what kind of assault the genetics of your body are under, every moment of your life. Certain chemicals, certain products of your own metabolism, denatured forms of certain enzymes, errors that occur during DNA replication, etc. DNA is a fairly fragile molecule. Most of the time it's stored in a highly coiled, stable state within your nuclei - packed away like a wedding dress - but it has to be "unpacked" to be read (for replication or transcription) and at that time, it's more vulnerable to damage. Factors that cause mutations, we call "mutagens." Mutagen - WikipediaI don't think there's a comprehensive list here, but this will give you some idea of what kind of mutagens exist. There's also a certain level of "background" mutation that exists because the mechanism of DNA replication that occurs during mitosis is not perfect, and it occasionally introduces errors into the daughter DNA.

Oops, yeah, typo. It actually is non-zero.

Oh, gosh, let me look it up...Yeah, that's what I thought. Blastocyst stage, about 4-5 days post-fertilization. I guess I was unclear. I meant this as an example of it decreasing the odds of your existence, as defined by your genome - since chromosomal crossing increases the number of potentially different gametes. Well, obviously she's going to resemble your mother more than you in the sense that she's a woman and you're not.But really it depends on whether or not a characteristic in question - like, say, whether she has "your eyes" or your mother's - inhabits the X chromosome. The X doesn't actually have a whole lot of genes, it actually has the least genetic density (that is, number of genes compared to total length) of any chromosome.A couple of genetic diseases are linked to the X chromosome. Without getting too off-topic, the most noteworthy is probably color-blindness, a nominally recessive trait. Unfortunately, because a man who inherits the recessive trait on his X chromosome only has the one chromosome, he is invariably color-blind. Male-pattern baldness follows the same pattern of inheritance, which is why you'll sometimes hear people tell you to look to your mother's father to see if you'll inherit it. (Your grandfather passed his single X to your mother with baldness "on it", and she stands a 50% chance of having passed it onto you.) They don't chain up. They exist in a normal cell as 46 individual lengths of DNA, all tangled up with each other like a ball of spaghetti. Typically they're the last chromosome pair listed in a karyotype:But that's just a convention that cytologists use, not a representation of biological reality. The long and the short of it is this - if not for mutations, all organisms would be clones of each other, genetically identical. Mutation is the sole original source of all genetic diversity - remember, diversity just means "individuals being different than each other." Mutation is ultimately responsible for all variation between individuals. The reason you are not my identical twin is because of mutations - not just your own, but the scores of mutations you inherited, all the way up your direct lineage. If Ambrose has some proof of it taking "five mutations per new feature", it's not presented in the article. Regardless, new function from single mutations is not unheard of. And if you're not used to thinking in terms of exponential population growth, this:

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Since only one mutation per 1,000 is non-harmful (Davis, 66), there would be only one non-harmful mutation in a population of 10,000 such cells. The odds that this one non-harmful mutation would affect a particular gene, however, is 1 in 10,000 (since there are 10,000 genes). Therefore, one would need a population of 100,000,000 cells before one of them would be expected to possess a non-harmful mutation of a specific gene.

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might sound like a steep hill to climb, until you realize that a population of E. coli doubling in size every half-hour hits well over 1 billion individuals in about fifteen hours.You, yourself, carry about 300 germline mutations that are specific to you, plus who knows how many mutations from each of your parents (and a countless number of somatic mutations, mostly in your skin. Use sunscreen.) So clearly there's no shortage of mutational variety in our genomes. Over several billion years of living things that's an incomprehensible number of genetic variations.

Actually most cells in the body can't replicate themselves. As part of the differentiation process, they often lose unneeded organelles. For instance, red blood cells have no nucleus.Some cells in the body are constantly replicating - bone marrow cells, hair follicles, the outer layer of your skin, the inner layer of your gastrointestinal tract. Yeah, 46 such strands. Each chromosome is a seperate strand. The only difference between you and the spider is the content and arrangement of your genetics."Moby Dick" and "Pride and Prejudice" are two very different novels, but consider the fact that they're both written with the same 26 letters of the English language.The genetic alphabet is only four "letters" long. The most surprising discovery of the human genome project is that the entire human genome is only about 15,000 genes. What I'm saying is, it doesn't take a great deal of genetic information to represent the difference between you and the spider. Yeah, but we find livers in every single multicellular organism above the level of a sponge; the intestine is simply a tube. The basic roundworm has an intestine, and it just passed it on down.The basic cell already has functions for filtering and disposing of waste, as well as for storing energy. So the function of the liver doesn't seem like a big mutational stretch.If you're wondering what gene it takes to specify a liver, I don't know myself. That would be a question of evolutionary developmentology, I think. Every single one of your body's cells, including each of your gametes. Of course, your gametes have mutations of their own that could be potentially passed on as well.Mutations all over the place, that's what I'm trying to get across.

Yeah, but not a whole order of magnitude more. For instance, compared to the 15,000 genes in the human genome, E. coli has something like 4000 genes.It takes surprisingly little genetic information, apparently, to describe the difference between you and bacteria. Cells are always gathering exterior material while they're alive, because their metabolic processes require a constant influx of food energy and raw materials. The cellular membrane isn't just a piece of Saran wrap holding the cell together; it's studded with little protein "doors" that only work one way. Some of them allow wastes to leave and some of them allow food to enter.So materials are always on their way in, and as you found out in that other thread, everybody's body - from the spider to you - is essentially made out of exactly the same thing. Sugars, proteins, fats. (These are all examples of macromolecules - large molecules that, like DNA, are made up of combinations of smaller, repeating constituent molecules.) PZ Myers is a evo-devo biologist from my hometown, and he writes a blog about politics and science. During the school year he also posts about genetics and developmentology, and I've found those posts very fascinating and accessible to the layperson. So that could be one more recourse for you: pharyngula | ScienceBlogs

If the phrase was actually "evolutionary developmental biology", then it would be "evo-dev-bio", now wouldn't it?Yet, that's not what they call it. Which makes it pretty clear that the field abbreviated as "evo-devo", expanded, would be "evolutionary developmentology", and it should be additionally obvious to anybody with a brain that "developmentology" would be "the study of development."So, you know, stuff it.

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