Questions on "Random" Mutations

Hi taylor, Random things are not necessarily unpredictable. For example a coin toss might give a random result, but we are able to predict, with narrow confidence intervals, the number of heads obtained after a few thousand tosses. Similarly, completely nonrandom processes are not necessarily predictable, chaotic systems being a good example. One often hears the phrase "random with respect to fitness". The random shuffling that you are thinking of is probably recombination, which is not a form of mutation but generates genetic diversity by its effects on redistributing diploid alleles within two haploid genomes. Remember you have a maternal and paternal copy of each chromosome. Imagine there are two genes on the maternal chromosome, called A and B. On the paternal chromosome you have a and b (lower case reflecting slightly different versions or alleles of the genetic sequence). When the paternal and maternal chromosomes align with each other during meiosis, some crossing over can occur. One of your sperm or eggs might end up with the combination A-b while another might end up with a-B. Neither of these combinations was present in either of your parents. Thus, recombination can increase genetic diversity by giving rise to new allele combinations in the offspring. Obviously recombination generally occurs during the production of sper m or eggs.As for physical causes of mutations, you are correct that factors such as radiation (including sunshine), toxins, etc. are involved. Obviously, if a mutation is going to be passed on to your offspring it must occur in the germ line (that is, in the sperm or eggs). The vast majority of mutations occur in our somatic cells (simply because we have more of them) and whether these are beneficial, neutral or cause diseases such as cancer, out children will not benefit or suffer from them. For this reason it is often believed that most mutations of evolutionary importance occur in the cell cycles involved in gamete production, before the embyo even exists.In principle, however, mutations occurring in the developing embryo might also be passed into the germ line. For example, when the embryo has only single cell, any mutation occurring in its genome will inevitably end up in the sex cells (which must develop from that single cell at some point). In a two-cell embryo there is a 50% chance of the mutation ending up in the sex cells. In a four-cell embryo the chance is 25%. Since the growth of cell number in an embryo increases at an exponential rate, I would expect that the chances of a somatic mutation ending up in the sex cells becomes vanishingly small quite quickly. After that, only mutations occurring directly in the sex cells will be relevant to evolution.An important form of nonrandomness in mutations is the result of the chemistry of nucleotides. Apparently it is energetically more feasible for mutations to convert from purines->purines or pyrimidines->pyrimidines than it is for mutations to convert from purines->pyrimidines or vice versa. For this reason, mutations like C->T or A->G tend to be several times more common than mutations like A->T. The mutation C->T is by far the most common single point mutation in the human genome. But these mutations are still "random" in the sense that the number of mutations from each class that occur over some period of time is a random variable drawn from some sort of probability distribution. The only thing to note is that each class of mutation has a probability distribution with its own characteristic mean rate.Another important kind of non-randomness results from the existence of "mutation hot spots" on each chromosome. Apparently some chromosomal regions accumulate mutations more rapidly than others. Regions with high levels of G and C nucleotides also tend to mutate less often. The number of potential mutations is, I suppose, limited by the size of your genome. But in practice mutation events are so rare that they are not constrained in this way. Developmental constraints, as you suggest are more important. You can see a list of developmental genetic diseases (and some photos) at this link. As you might imagine, mutations that badly disrupt the developmental system of an organism will likely compromise future reproductive output severely. However developmental processes are quite plastic - they can often adapt to minor and even major disruptions of the developmental program. In her book "Developmental plasticity and evolution" Mary-Jane West-Eberhard describes a bipedal goat whose developmental system was able to accommodate a genetic or environmental disruption to its front leg formation, resulting in upright walking! So it's probably more correct to say that the number of functional mutations is limited by the extent to which the developmental program of the organism can accommodate peturbations. I'll see if I can find the photo of the goat and post it here - it's quite cool.As to your last point, I don't see why we would expect "more evolved" animals to have more plastic developmental programs. In fact we might as well expect the opposite, with an animal becoming more and more adapted to some specific niche from which it cannot depart without catastrophic consequences. Nature doesn't care about being ridiculous. We don't have fire-breathing lizards but we do have glow-in-the-dark jellyfish and chameleons whose skin can change color to match the background. There is a jumping millipede, and a kind of frog that curls into a ball and rolls away to avoid predators (though that may have been from Labyrinth, I tend to get reality and Jim Henson mixed up). What more do you want?On dragons, there is a quirky book by Peter Dickinson called "The Flight of Dragons" in which the biology necessary for the fire breathing and flight of large reptiles is exhaustively described. I don't remember the details, but he made it sound quite straightforward, as long as breathing fire and being filled with hydrogen is not an evolutionary liability. The book was somehow turned into a cartoon.Mick

Just a thought - I often hear the suggestion that up to 100 nucleotides differ between parents and their offspring. Presumably this means that each sperm differs from every other sperm (or each egg from every other egg) by around 50 nucleotides. Does that also imply that every cell in one's body also differs from every other cell by around 50 nucleotide substitutions (assuming that each cell has undergone the same number of cell divisions prior to its differentiation)?What do you think?Mick