 on the computer is showing 12, so I think it's 12 central time. So I think I'll go ahead and start. Is that okay, Chantal? I remember smallpox vaccines, too. In fact, the first time I fainted when I got a shot, it was a smallpox vaccine. Okay, well, what I'd like to do is tell you about a little project that I did several months ago and thought I would just share it with you. It's a little strange, but I enjoyed it, and I thought that some of you might enjoy it, too. The first thing I have to do is get out of the way of my arrows. Okay. Okay, as you all know, mutation is the change in a DNA sequence. And mutations are important because the differences that distinguish one organism from another are mostly arrived at by mutations. The origin of most differences in DNA sequences. DNA sequences have the information to make us all who or at least what we are. Mutations occur mostly randomly. They can occur during DNA replication itself, just by replication error, or sometimes by chemical modification or by radiation. Most mutations are single nucleotide replacements. That is, one base in the DNA is replaced by another base. And if a mutation occurs in a protein-coding gene, then it can change the protein by changing the encoded amino acid. And then if that occurs in a gamic-producing cell, then it may be inherited. If it's just produced somewhere else in your body, then it won't be inherited, but you might suffer from it. So a lot of genes are protein-coding genes, and they determine the amino acid sequence of proteins. Amino acids are the structural unit of proteins, and a protein is just a long string of amino acids that are sort of all filled up. One of the examples we're going to be looking at this morning is beta-globin. And beta-globin is one of the two molecules in the oxygen-transport protein hemoglobin. And the reference coding sequence for beta-globin is showing here. And then below is the translation. And you'll notice that the DNA sequence is a lot longer in the protein sequence because there are about three bases for every amino acid. So what sometimes happens when you get a change in a base, like here's a three-base codon. You have three bases per amino acid, and those are called codons. And if one of these changes to a different codon that a different amino acid may be produced, for example, one example that I think Stephen actually mentioned last time is the mutation that occurs in sickle cell disease. You get an A in the DNA codon changing to a T in the codon of the sickle cell gene. And this changes the amino acid from glutamate, which is the E, to valine, which is the B. So that is a typical amino acid substitution that you sometimes see. And sometimes these substitutions are consequential. It may affect how the protein functions, reduces the function of the sickle cell gene, although it does also make individuals who carry it resistant to malaria. Another kind of mutation is what you see in the next line. So you've changed the GAG to a TAG. And in this case, there is no amino acid substitution. What you get instead is what's called a stop codon, a stop signal, so that when the protein is translated on the ribosomes, the ribosome sees that signal and says, okay, I'm done. And those are nearly always very destructive of the proteins, unless they occur very late along the sequence. And then finally, you have an odd little mutation, which you see in this fourth line here, where you have GAG changing to GAA. And in this case, although the codon has changed, the amino acid does not change. And this is what we call a silent mutation. So you have had a mutation, but it has no effect on changing amino acid sequence in the protein. They're called silent because they don't change the amino acid. The reason that some mutations are silent is because of the structure of the genetic code. So in the universal genetic code, there's 20 amino acids, which you see in these little blue three-letter signals, alanine, threonine, proline, serine. And each of those is encoded by a three-base codon. What you find is that these codons come in blocks. So there are 64 codons and only 20 amino acids. So on average, there's three amino acids per codon. In real life, it's more like sometimes there's four and sometimes there's two. So these four blocks here have four amino acids or four codons for amino acid. These little half blocks here have two codons for amino acid. And then there are a few codons, which are stop codons. There are only three of these in the universal code. So if you change this third base in the codon, you may not change the amino acid. And especially if you change it for the same kind of base. And notice that these two half blocks always occupy either the upper or the lower part of the coding block. So these two both end in purines, adenine or guanine. These two both end in pyrimidines, which are uracil or cytosine, uracil because this is the RNA version of the code. So sometimes you have two, sometimes you have four, sometimes you have three, sometimes you have one, sometimes you have six. But on average, there are about three codons for amino acid. And this this repetitiveness in the code is because it's why you can get a sonic mutation. So if you change this base to this base, it won't change the amino acid. And that works because of the way that proteins are translated. Proteins are translated using another kind of RNA called transfer RNA. And transfer RNA carries an amino acid and matches it up with the messenger RNA codon on the ribosome. And so the structure of the code is actually enforced by the transfer RNAs. That's where the code actually exists, using what transfer RNAs match up with what messenger RNA codon. So some of these transfer RNAs can match to more than one codon. And this partial mismatch is called wobble. But if you've got two or sometimes three similar codons, the same tRNA can add the same amino acid to both opposite both. So that's what some mutations are silent. This is just a quick summary of some of the wobble rules. And you'll notice that in the anti codon of the transfer RNA, the anti codon is a three base sequence on the transfer RNA that matches with the three base sequence on the messenger RNA. And the third base of the messenger RNA codon, or the first base of the transfer RNA anti codon, is the wobble position. So that base in the anti codon position can be one of lots of different modified bases. Transfer RNA has a lot of funny bases, which is not true of most other RNAs. The transfer RNA is kind of weird in that respect. And why that is a total different story, so I won't go into that. This next slide is just a picture of some of those funny bases. A lot of them are just methylated versions of the regular base. So this is methyl adenine. This is methyl guanine. This is methyl ionicine. This is ionicine un-methylated. And you can see that ionicine is appearing. It looks a little bit like adenine and a little bit like guanine. But this is just some of the funny bases that you find in transfer RNA. Okay, so how did I get interested in these silent mutations? Last semester, when I was teaching my non-major genetics course, I asked the student a question. And if you look at the same protein coding gene in two different species, which is going to be more different, the coding sequence of the DNA or the amino acid sequence of the protein. So in the genetic code, you have three bases per amino acid. So if you have a coding sequence of 300 bases, that would give you a protein of 100 amino acids. So generally, if you make one base change, you might get one amino acid change. And since the proteins are only as third as long as the coding sequence of the DNA, then you would expect to find actually more change on a percentage basis in the amino acid than you find in the DNA. So if you had 30 bases, 30 changes in a DNA, then that would give you 10%. If you changed 30 amino acids, then that would give you 30%. So that's what I wanted them to think about was that difference in structure and the difference in number and how that's reflected in the percentage of different DNA. Since there's more than one codon for amino acid, and since you have either usually either four or two codons for amino acid, you have an average number of three codons for amino acid. So changes in the third base of the codon don't usually change your amino acid. So only two-thirds of the time are you going to get a mutation that will change your amino acid. So if we have 30 mutations in a 300 base coding sequence, you still have 10% of the DNA, but now only 20 of those changes will change the amino acid. So the protein still changes as a percentage by more than the DNA. But generally, it's one amino acid change per DNA change. So that's a testable hypothesis because we have, for many species and for many proteins, we have the coding sequences of their DNA and we have the amino acid sequences of their proteins. And as you know, or as you may know, I love to snoop in the databases. And this is a question that can be answered by snooping in the databases. Excuse me, I've got a big dog in my lap right now. And so I thought, well, I'll just check and see if that is the situation. But if you get 30 base changes, you'll only have 20 amino acid changes. So this is what I learned by looking for the databases. And it turned out to be interesting. Okay, so mutations are different in different species because once species separate, once the lineage in which two species are found have separated, then they can accumulate different mutations just at random. So if these mutations occur more or less randomly, then the longer any two species have been separated, the more mutations will occur between them. And because of that, we can use the number of differences in DNA or in protein sequences to look at the relative relationships between organisms. So this is the basis of molecular phylogeny. So on the next slide, there's a sample phylogeny based on the beta-globins of 12 species, humans, dogs, horses, cows, camels, llamas, whales, dolphins, seals, rhinos, and gibbons. And here is that phylogeny. And in this, the two species that are most closely related will be on a single fork, like this one here, where you have humans and gibbons. This is hyalobates alarm, which is a gibbon. And humans and gibbons only differ by two amino acids in their beta-globins. Interestingly, camels, bacteria and camels, and llamas also differ by only two amino acids. So this length here represents two amino acid changes. So if you look at this difference between rhino and horse up here, you can see it's about six times as long as the one between humans and gibbons. And so there are about 12 amino acid differences between humans and horses. And then the most distantly related pair is hippos and camels, which is here. All right, so these are all due to mutations that produced in amino acid change. So how do you find the differences that don't produce in amino acid change? How do you find the silent mutations? So I'm just going to tell you this story of three proteins, beta-globin, amylogenin, and rhodopsin. And how those compare in two rather divergent mammalian species. They just look similiaris, or dogs, and humans. So we'll be looking at these three proteins and their DNAs and in these two different species, humans and dogs. So this is the beta-globin sequence, the protein sequence for beta-globin and humans. And down below that we have an alignment between the human and the dog beta-globins. And the middle line in this alignment tells you how many of these amino acids are not changed. So if it's the same as the top and the bottom line, then they're not changed. But if you've got a gap in that middle line, or if you have some other symbol in that middle line, then that represents a change that has occurred. And the first four of those are marked with these little arrows here. I didn't go through and mark them all. The first four. So if you go through these two proteins, you can see that there are 15 differences between the human and the dog. And they're in different parts of the sequence. So what does the DNA look like? This is the beta-globin coding sequence, the part of the DNA sequence that is translated on the ribosome. No, split, split. Not talking to you, talking to the dogs. Okay, so this is the beta-globin coding sequence in humans and in dogs. And you can see there are a number of differences here. And there are 53 differences. 15 of those are reflected by amino acid changes. So if only a third of the mutations are silent, then there should just be a lot fewer silent mutations. There should be about eight silent mutations here. And there are a lot more because 38 of these differences are not reflected in amino acid change. They're exactly the same, even though the DNA's are different. So this is amylogin. This is the protein that puts the enamel on your teeth. And if you compare the human and the dog proteins, there are 17 differences. Now in this case, one of these differences is in a gap. That gap is right here where there's a skip over an amino acid. So a whole codon is missing in the human sequence that is present in the dog sequence. So only 16 of these differences are actually in the amino acid sequence. So I'm just going to ignore the gaps. So we've got 17 differences in the amino acid sequence. And here's the amylogin and coding sequence. And it's somewhat similar to what we saw in beta-globin. There are 39 differences, but three of those are in the gap. So we're only going to count 36 of them. And there are only 20, or I'm sorry, there are only 16 differences in the amino acid. And the other 20 are silent. There's too many silent mutations. Let's look at one more protein. And this is rhodopsin. This is the light-sensing protein that you use for your night vision. It's in your retina. And it's a bigger protein. It's 300-and-something amino acids long. And again, there are 16 amino acid changes in the sequence. However, there are a total of 26 differences, but 10 of those are in this big gap that's right here. So there's a big chunk that's missing from the human protein that's present in the daughter protein. So if you're looking only at the coding sequences that are found in both species, there are 16 amino acid differences. And in this case, since it's a bigger protein, it's a bigger coding sequence, and that actually takes two pages, and I'll show you the second page in a minute. But overall, there are 30 amino acids or 30 bases in the gap and 76 in the coding sequence. So only 16 of those produce an amino acid change, and the other 60 codon differences are silent. So there are more than ought to be. Oh, this is just the rest of that Rhodopsin sequence. Okay, so this is the rest of the Rhodopsin sequence, and you can see that there are a lot of gaps in here. Okay, so I'm just going to look at a translation of part of the Rhodopsin sequence. So this is 1, 2, 3, 4, 5 lines of code. They're divided into the individual codons. And each of the codon differences is in bold type, and each difference that gives rise to a different amino acid, the different amino acid in the dog is shown below. So we've got isoleucine in humans, we've got valine in dogs, we've got valine in humans up here, and methionine in dogs. So these red ones are the ones that are different. So in these five lines of sequence, there are 25 mutated codons or 25 mutations, and five of these results in substitutions and the other 20 are silent. So why is this? Well, wait, let's back up. Let's just look at a summary of those differences to begin with. So here you've got the three proteins. These are the number of amino acids in the protein. So Rhodopsin is about twice the size of the imutative. And these are the coding sequence differences, and these are the amino acid differences. And in each case, there's many more silent mutations, and there are non-silent mutations. But those are all relatively small proteins. So I also looked at one larger protein. This is the cystic fibrosis transmembrane regulator sequence, which is a chloride transporter in the cell membrane. And it has almost 1,500 amino acids. There are 468 coding sequence differences and 147 differences in the proteins. So that is roughly between what we see in amylogeum and what we see in beta. And again, there's just way more silent mutations than there are non-silent mutations. So why are there so many silent mutations? Why do the silent mutations prevail? And there are three possible reasons that we can look at. Wait until that comes into focus for me at least, hoping that it will also be in focus for you. Focus, focus, focus. Here it goes. Okay, can you all see it? All right. So three possibilities are that silent mutations may be more common because of the chemistry of mutation. That is, maybe you're just more likely to get a silent mutation than you are to get non-silent mutation. And the code also produces a certain number of silent mutations. That's one possibility. Another possibility is that if you get side-by-side mutations in the same codon, it's only going to be expressed once. So not all mutations that are unexpressed are really silent mutations because if you have two mutations in the same codon, you are going to have a different amino acid. And then finally, silent mutations may be more common because there is very strong natural selection in favor of not messing with the protein. So in most cases, if you do change the amino acid, or if the mutation does change the amino acid, the individual that's carrying that mutation just dies. It's not compatible with survival. So these silent mutations are the surviving mutations and the other non-silent mutations that we don't see in these proteins are the ones that kill you. Okay, so we're just going to take a quick look at those three possibilities. And the first has to do with the structure of the code in the chemistry of mutation. So when you get a base change, either due to chemical interference or radiation or just an accident of replication, you're more likely to get a transition that is a purine for a purine or a pyrimidine for a pyrimidine than you are to get what's called a transversion in which a purine changes for a pyrimidine. And if you look at the structure of the code, you see that any time you've got just two codons or a given amino acid, it's either two pyrimidines or it's two purines. And so if you change that, you're more likely to change it to another purine or to another pyrimidine than you are to change the different kind of base, which is more likely to give you mutation. So that's one thing. And also, of course, transitions in a third position are very likely always to be silent because of the structure of the code. So let's look at the transitions and the transversions in that Rhodopsin sequence that we looked at a while ago. These are the five mutational changes that you see in the sequence. Again, the mutated codons are in boldface type and the transversions are marked with TB over the codon. Everything that's not marked with TB is a transition. So of the 25 mutations, only six are transversions, but you would expect that maybe they would all be expressed by an amino acid change, but only one of those is associated with an amino acid change. And the other four differences in this sequence are all due to base one transitions. So it's these base one transitions that have actually caused more mutations than the six transversions. So it's not just due, at least in this particular passage of DNA, it's not just due to the chemistry. So the second thing we can look at is how often do you get two mutations side by side, so you're only going to get one change if you get any change in the codon. And in the proteins that we looked at, the beta-globin sequence has the most clustering. We're going to look at how that clustering contributes to amino acid changes in the protein. So this is the whole coding sequence for beta-globin. And the codons that have more than one base difference in them have been underlined. So these are the cluster codons. For example, there's three. There's three changes in this one here. There's two in this one here. There's only one in this one here, so this is not underlined. Okay, so everything is not underlined. It just has a single base change. And the others have two or three. So of those 53 nucleotide substitutions, only 42 codons are actually changed. And all of the eight codons that have more than one change, you get an amino acid change. So of the 15 amino acid changes, eight of them are due to multiple changes in the sequence. So they will all change. And all of the multi-change codons will change the amino acid. But of the 34 nucleotide changes that you see, single nucleotide changes that you see in these codons, 80% of them are still silent. So it's not just due to clustering. So even the single changes predominantly are silent mutations. So our third possibility. Oh, sorry. All right. So if you're assuming random mutation, then about a third of the mutations should be silent. And mostly those should change only the third nucleotide of the codon. In the beta-globin gene, there are 10 first-position mutations, eight second-position mutations, and 34 third-position mutations. There are three times as many mutations in that third position than there are in the other two because changing the other two will change the amino acid. So silent mutations seem to be very strongly selected. So most changes, what that means is that most changes that do change the amino acid are going to kill you. So Darwin wins again. Now we've only looked at four proteins in two species, humans and dogs. Humans and dogs are in two different branches of the mammalian phylogenetic tree. Humans are in the U-Archontogleres, and dogs are in the Eurasian theory, which are two of the three major branches of the mammals. So here's the U-Archontogleres up here, and that includes the primates, which is everything in red, and rodents and rabbits. So humans and mice are basically in the U-Archontogleres, and there's the human sequence up here. And a dog is down here in the Eurasian theory. So the U-Archontogleres in the Eurasian theory diverged from each other about 90 million years ago. So they've been separate for a long, long time, a lot of time to accumulate mutations. And yet we only see a number of sonic mutations, plus just a few amino acid changes. So that's just a reflection of the tolerance of proteins for amino acid changes in their sequence. Some proteins are more tolerant of change than others. For example, the histones are very intolerant of change. The histones in all species are very similar. So if you change one of those, you're going to break the protein. But amelodgenin and rhodopsin are relatively tolerant of some change. Oh, I actually see a question. Is there any way to determine if a sonic mutation in a third spot later switches to a mutation in which one or two are then changed? I think the way to track that would be to look at species that are more closely related, which most of the mutations are silent, and then look at more distantly related species to see if a second change in that same codon has produced a change in another species. So you could track it down. So there could be a mutation that is silent in one species but not silent in another species in the same codon. Is that the question? So you could start with a silent mutation and then get a non-sonic one. But two-thirds of the time you're going to get a non-sonic one, and most of the time that's going to kill you. So about 10%, and I'm actually surprised it's this high at that, so about 10% of mutations that change the amino acid sequence are survivable and the others are not. Okay, so I could stop here and take questions, or I could go on to this last question, which is, are sonic mutations really totally silent? That is, does the fact that you don't change the amino acid mean that you don't change the protein at all? It wouldn't seem to be changeable because if you haven't changed the amino acid, why would it change the protein? But there are some effects that sonic mutations can have on the protein. And this again has to do with the transfer RNAs. So the transfer RNAs have to match, they're very fussy molecules. They have to match two different binding sites. They have to recognize the tRNA binding sites on the translating ribosome, and they also have to recognize the binding sites on the enzyme that puts the amino acid on the tRNA. These are the aminoacyl tRNA synthetases. And so you've got to slot that transfer RNA into both places. So the structure of that tRNA can be quite fussy. And if you look at the codons that are used in different species, and these are the codons that you actually find in the human genome. So for example, if you look at all of these alanine codons, nearly half of them are GCC. And the other three codons are only used about half as often as GCC is used. So this is favored. In these valine codons, GUG is the favorite codon. And in this leucine codon, and there are six leucine codons, these two up here and these four down here, 40% of those codons, even other six of them, are CUG. And in this one over here, you have the glutamine, two glutamine codons. And 73% of those, or three quarters of those, are the CAG codon. In other cases, you may get about equal numbers. For example, these two asparagine or these two lysine codons are somewhat different, but they're more similar than some of these others. So in some cases, there are favored codons. So what if you switch out a favored codon for a non-favored codon? Why is this a favored codon? Because that's the one that the RNA likes. So if you switch to a less favored codon, then maybe the codon-anticodon interaction is going to slow down a little bit. The protein won't get made as quickly, or it might, the protein folding, the company's translation may be slowed down a little. So you may not alter the protein itself, but you may alter the quantity of the protein that gets made if you have silent mutations. So it's possible that silent mutations do have some effect on the field. Oh, does that extend to plants? Oh, that's a very good question, Phil. You know, you could actually do that experiment. I'm going to look at different proteins in plants and see the ghost replants, too, because those proteins still have to function, even though they're in plants. I would guess that it does go for plants, but it's an excellent question. And I'm going to show you the links to the software that will let you compare those. So this is OMIM. OMIM is online Mendelian genetics in man. Yes, it is man, sorry. But this is all of the DNA sequences and protein sequences for human genes. So humans are all in OMIM. This was where I found the codon usage, and this is what you want to use to do the comparisons. The BLAST software is free. You can download it or you can use it online. If you just type in NCBI BLAST, it'll take you right to it. You can actually Google it. Yeah, I suspect that there is codon preference for plants. I suspect that there is. Anyway, so if you wanted to try out some of these, you are certainly welcome to do too, because it's all free. It's all taxpayers for it. And so there it is. Okay, you have a question about reclassifying a coding sequence to become a non-coding sequence. If, oh, I think the question you're asking is that you may be, would a difference in RNA preference make a coding sequence in one species be a non-coding sequence in another species? Is that the question you're asking? Okay, say it again. What do you mean when you say reclassify a coding sequence to become a non-coding sequence? Yeah, quite a lot of the DNA in most of the male genomes is not protein coding. Only about 25% of the DNA sequences are protein coding genes. And in those sequences, most of those are, most of that sequence is introns, especially in the big genes, which is not part of the coding sequence. It's non-coding DNA, which is spliced out of the messenger RNA, which is then translated into the protein. A coding sequence is a sequence that encodes a protein. So if you've got a chunk of DNA that doesn't encode a protein, then it's non-coding DNA. Now there's some question about what you should call regulatory RNAs, because they don't encode proteins, but they're also functional. They're also functional, as you know, they do things, they're regulatory molecules. So those are functional molecules that are not proteins. Not unless you, oh yes, you could change it if you get a mutation in a transfer RNA. If you get a mutation in a transfer RNA, then it will either put in a different amino acid, or it might put in an amino acid, it might put in a stock codon. So, and you do get transfer RNA mutations. Now you have a lot of copies of your RNA genes. There's a bunch of different transfer RNAs, and you have multiple copies of all of them. So if you lost one, it might not be too serious, but if you lost an important one, and you changed it into something else, it could screw up the translation. But it would only be in that one cell. Unless, of course, it's an organic producing cell, which would be in you and all your children. No, they don't recognize mutations at all. The only thing that they recognize is mismatches between the two sides of the DNA. So the DNA polymerase, for example, will go along and plug in the bases, and if it makes a mistake, it can back up and fix it. Which is why RNA viruses are more mutable than DNA viruses, because the RNA polymerases don't have that correcting function. So they don't say, oh, that's a mutation. They just know that it does match, it matches the other strand. As long as it matches the other strand, they're okay. It might make an annoying beeping sound, I don't know. Well, if there are no other questions for now, I actually have a few more slides that I didn't include in the regular talk, and it has to do with excellence in introns. I mentioned to you that the coding sequence includes only the exons, so only this red underlined part here gets into the messenger RNA and gets translated into the protein. Yes, double-stranded DNAs are more resistant to mutation. So yes, the answer to that is being double-stranded is probably the reason why DNA replaced RNA as the genomic material. Billions of years ago. Did that answer your question, Suzuki? Yeah, it's really interesting. The RNAs are catalytic. They can catalyze some chemical reactions. And so they serve some of the functions of proteins and some of the informational functions of the patient. And that was taken over. Those two functions were both taken over by other molecules out of RNA world. Now we do catalysis with most catalysis. There are still some cattle in the car. The most catalysis proteins. And we do most genomes with DNA. There are some, as you know, there are some viral genomes. But most genomes are DNA. Yes, the changes that do change the function of a protein in a way that is advantageous are the same kind of mutations. For example, and actually rhodopsin is kind of an interesting one to look at in that case because different animals are sensitive to, especially their cone opsins, the red, green, and blue opsins are very sensitive to different wavelengths of light. And if you change those, they're sensitive to different wavelengths, then that would give you the ability to see stuff that you couldn't see before, like you get ultraviolet vision, which a lot of insects have. That's how they identify their flowers by the ultraviolet patterns on the flowers. And some rodents, I think, can see ultraviolet. And that's because the function, one of the functions of being able to do that is that when they track around, they sort of pee on their feet and leave busy footprints as they run around. And then their family can keep up with them because they can't see those footprints because they're urine fluorescent. And the mice can see that. You can't see it, but the mice can see it. So yes, you can acquire new functions. And in fact, the red cone opsin in humans is a duplication of the green cone opsin, which has then changed its sensitivity, changed its spectral sensitivity so that it can see red light. And yes, you could change it to seeing UV. In fact, a lot of people have extra, two or three extra green genes. And it'd be really interesting if some of those green genes became ultraviolet sensing genes. Certainly possible. So they could see infrared or they might be able to see ultraviolet. No kidding. That's interesting. Cataract surgery, so replacing the lens, gives you more UV sensitivity. Well, I've had cataract surgery. I'll have to go look at some UV sometime. I'll have to go out and look at the flowers in the dark and see if I can see any. No, that's true. You shouldn't look at it without your glasses on or if I have my glasses on, then I can't see it. Thanks for that reminder, Sissy G. Well, it's an interesting question. And I think the ultimate fate of those extra green genes is an interesting question. If we survive as a species for another million years, we might indeed develop new powers. We don't use blue-sensitive photosensors for vision or we don't use them just for vision or that different blue-sensitive photosensors. With color blindness, most color blindness either do a change in one of the color receptors, either the red-green or the blue. And the red and the green are both side-by-side on the X chromosome. They may simply change, just get a mutation that alters it so that it's non-functional, but mostly the gene is deleted. Mostly if you're red insensitive, then all or part of the red gene or all or part of the green gene has been deleted. Oh, what island is that, Shiloh? The island of the color blindness. Steven, what does that reference? Well, sometimes islands are colonized by very small groups of people and so they get very inbred. Cryptochrome blue light photoreceptor. Oh, okay. So it's a different kind of blue photoreceptor. Cool. Do you know where's chromosome it's on? The regular blue gene is on chromosome 3. Fingalaphtone. Very interesting. What kind? Is it red or green? I don't know what kind of color blindness he has. It's probably red-green. Blue is a curse, but it's very rare. Red-green color blindness is so common because it's X-linked and so a lot of males have it. I actually have a colleague who is completely, totally colorblind. He does not see colors at all and I don't know what his... I don't know why that is. Color blindness is inherited, yes. About one out of 12 males is colorblind. Acromatopsia. He colors it all. Boy, that would be sad. It would be sad not to see colors at all, I think. I don't know. Maybe if you've never seen colors, you don't notice. My pleasure. I just enjoyed the little project and I thought, oh, the next time Chantal asks for a presentation, I'll cue that one. It's kind of nerdy. Yeah, I try to be careful when I'm making slides for students, not to use red or to use a red that's visible, like that dark red that's up there. Thank you, thank you. Oh, yes, Chantal. I so appreciate everything you do to put these on because I know it must take a lot of work. Oh, what's the fourth color, Steven? Are they ultraviolet? Yeah, we don't necessarily have the best color vision in the world. Or the best anything, as long as that goes. Look at that. Ultraviolet, okay. Very interesting. It would be. In fact, I wouldn't be surprised if some nocturnal predators didn't have colorblind infrared vision. No, your night vision is deodorodopsin. It's a different protein. So some of those green genes are turning into something else. Cool. Oh, yeah, like the raptors have terrific resolution in their vision, way better than ours. And sharks have, and a lot of other fish have magnetic receptors, electrochemical. So, Sherry, do you know what the fourth color is in human females that have tetrachrome vision? I'm going to Google that. Oh, they can, yes. Snakes can follow heat, heat signals. I just saw a couple calling this muscle. Great question. You all asked really good questions. Oh, thank you, Phil, for that article. Thank you all for coming. Got that bookmarked. Well, I do love to snoop in the databases. I always think of snooping in the databases like going into the attic and finding your grandmother's old love letters. Yeah, that's true about about frame shifting. There are some genes in very small viruses that actually overlap. And so they have to be read in different frames in order to be read correctly. I always learn more from the questions that people ask here that I do from doing a presentation. Fascinating, Stephen. I'm reading a thing about eye surgery. People that don't have a lens and so they can seal through my lip. Ooh, tetrachromates see 100 million colors. That's pretty impressive. 15% of women. Wow. Between the red and green cones. Okay, so it is that it is that extra green gene that has produced it. So it's already changing. Oh, my God, that is so cool. Fascinating. Thanks for that little tidbit, Stephen. That is really interesting. Oh, yes. We're having a talk back on fireside on Wednesday. Well, Phil, it was a fun project. Actually, I'm going to give it again to probably a reduced version to the faculty when we do our University College Day this spring.