1 00:00:00 --> 00:00:04 So, we have another kind of very interesting piece of the course 2 00:00:04 --> 00:00:09 right now. We're going to continue to talk about genetics, 3 00:00:09 --> 00:00:14 except now we're going to talk about the genetics of diploid organisms, 4 00:00:14 --> 00:00:19 which apart from bacteria, most of the organisms including us are 5 00:00:19 --> 00:00:23 diploid. They have more than one copy of each chromosome, 6 00:00:23 --> 00:00:28 and so we'll go through a segment on this, and also talk about mitosis 7 00:00:28 --> 00:00:33 and meiosis, the central processes of cell division and the segregation 8 00:00:33 --> 00:00:38 of genetic material that underlie life as we know it. 9 00:00:38 --> 00:00:42 And then, were going to charge into a session of recombinant DNA, 10 00:00:42 --> 00:00:46 and some of these technologies, PCR and various things that you see 11 00:00:46 --> 00:00:50 in the newspapers all the time. And then, I'll finish up with the 12 00:00:50 --> 00:00:55 session on the immune system, which a few of you thought was 13 00:00:55 --> 00:00:59 surprising that bacteria recombines. I'll tell you in that system it 14 00:00:59 --> 00:01:03 will feel like science fiction relative to what I've told 15 00:01:03 --> 00:01:08 you up to now. It's an absolutely amazing system. 16 00:01:08 --> 00:01:13 So, we are going to start today with genetics of diploid organisms. 17 00:01:13 --> 00:01:17 So I'm going to go back to how this was first understood. 18 00:01:17 --> 00:01:22 And most of you have probably heard of Gregor Mendel, 19 00:01:22 --> 00:01:27 who discovered this, and surely some fraction of you have 20 00:01:27 --> 00:01:32 run into an exposure to this topic before. But in keeping with what 21 00:01:32 --> 00:01:37 I'm trying to do in this course, could you guys watch out there? 22 00:01:37 --> 00:01:41 I think I'm just going to unplug, yeah, it's OK. I think I'm just 23 00:01:41 --> 00:01:45 going to unplug it for just a minute here. You've probably heard of 24 00:01:45 --> 00:01:49 Mendel. Some of you have seen these different squares. 25 00:01:49 --> 00:01:53 You might have memorized it from a textbook or something like that. 26 00:01:53 --> 00:01:57 I'm going to try and see if we can go through this material up another 27 00:01:57 --> 00:02:01 level of sophistication because, again, and I'm saying, science 28 00:02:01 --> 00:02:05 didn't just come down from on high and end up with facts 29 00:02:05 --> 00:02:09 in a textbook. What's in a textbook is somebody's 30 00:02:09 --> 00:02:13 effort to take a current state of understanding which is based on 31 00:02:13 --> 00:02:17 experimentation and come up with models. And what you're seeing in 32 00:02:17 --> 00:02:21 the textbooks are the models such as they were as of the time the 33 00:02:21 --> 00:02:25 textbook was submitted for publication. Sometimes they change 34 00:02:25 --> 00:02:30 even before the textbooks get out. But anyway, it's a process. 35 00:02:30 --> 00:02:33 Mendel was one of the starting people who started this process, 36 00:02:33 --> 00:02:37 really a key figure, and a guy with an amazing intellect. 37 00:02:37 --> 00:02:40 But before we start in, I just want to show you a couple of 38 00:02:40 --> 00:02:44 pictures because these kind of knocked me over when I saw them. 39 00:02:44 --> 00:02:47 I don't know what kind of image you have of Mendel. 40 00:02:47 --> 00:02:51 You probably know he was a monk, and he did something with peas, and 41 00:02:51 --> 00:02:54 he figured out this stuff about genetics. And most people probably 42 00:02:54 --> 00:02:58 carry around an image probably somewhat like this sort of 43 00:02:58 --> 00:03:02 romanticized drawing. He was a monk all right, 44 00:03:02 --> 00:03:07 but it was at an Augustine monastery in Bruno in Austria that was a very 45 00:03:07 --> 00:03:13 major intellectual center. They even published a scientific 46 00:03:13 --> 00:03:18 journal. They sent Mendel off to Vienna to go to university. 47 00:03:18 --> 00:03:23 While he was there, he studied physics, math, 48 00:03:23 --> 00:03:29 as well as botany. So he had, in many ways, 49 00:03:29 --> 00:03:34 a background that is very similar to you guys, very heavy on the 50 00:03:34 --> 00:03:40 quantitative physical science, mathematical sort of background. 51 00:03:40 --> 00:03:44 And then he went on to do some experiments in biology. 52 00:03:44 --> 00:03:48 And I think you maybe can get a sense of this. 53 00:03:48 --> 00:03:52 You can see a picture of what Mendel actually looked like. 54 00:03:52 --> 00:03:56 Here's one picture of him. But the one that really blew me away, 55 00:03:56 --> 00:04:00 I have a picture of the monks. Just think of what ever image you 56 00:04:00 --> 00:04:04 had of the monks that Mendel was at. 57 00:04:04 --> 00:04:07 Well there's a picture of them. To me, they look nothing so much 58 00:04:07 --> 00:04:11 like a group of university presidents or something sitting 59 00:04:11 --> 00:04:14 around for a portrait. And he traveled very widely. 60 00:04:14 --> 00:04:18 Here he was on his way to London here. Here is a picture of him with 61 00:04:18 --> 00:04:22 a group of people on his way to, I think he was in Paris on his way 62 00:04:22 --> 00:04:25 to London. So this wasn't a little isolated monk in a garden who 63 00:04:25 --> 00:04:29 stumbled across stuff. He was a rather sophisticated guy 64 00:04:29 --> 00:04:33 going after some interesting problems. 65 00:04:33 --> 00:04:37 And this was the garden in which he did his experiments. 66 00:04:37 --> 00:04:42 Here's a picture of it. So this was a straightforward 67 00:04:42 --> 00:04:47 experimental setup for these really amazing things he did. 68 00:04:47 --> 00:04:52 So, with that kind of background, Mendel was interested in a problem 69 00:04:52 --> 00:04:57 of inheritance. And people have been aware that 70 00:04:57 --> 00:05:02 traits were inherited. That was the whole principle of 71 00:05:02 --> 00:05:06 domesticating animals and domesticating crops, 72 00:05:06 --> 00:05:11 that if you took parents with certain characteristics and crossed 73 00:05:11 --> 00:05:15 them together, the offspring then had the traits 74 00:05:15 --> 00:05:20 that were associated with the parents. And so people have able to 75 00:05:20 --> 00:05:24 get better domesticated animals or better domesticated crops. 76 00:05:24 --> 00:05:29 But up until then, this mixing was thought of sort of like blending 77 00:05:29 --> 00:05:33 liquids, stir together some green and red, and a little 78 00:05:33 --> 00:05:38 this and that. And it all stirred together. 79 00:05:38 --> 00:05:42 And as you'll see, what one of Mendel's great insights was, 80 00:05:42 --> 00:05:46 was that it wasn't like mixing liquids. And to study this problem, 81 00:05:46 --> 00:05:51 then, he picked a system. It wasn't that he was just fiddling around 82 00:05:51 --> 00:05:55 with peas. He was a pretty sophisticated guy, 83 00:05:55 --> 00:05:59 and he picked peas as an experimental organisms 84 00:05:59 --> 00:06:05 for three reasons. And so, why peas? 85 00:06:05 --> 00:06:11 Well one, they were easy to grow, and that's still a major 86 00:06:11 --> 00:06:17 consideration of any model system that you want to use and science 87 00:06:17 --> 00:06:23 today. It's really tricky to grow, it's very hard to work with. It was 88 00:06:23 --> 00:06:30 easy to pollinate in a controlled way. 89 00:06:30 --> 00:06:35 Just the structure of the pea flower makes it very easy to make sure to 90 00:06:35 --> 00:06:40 either put the pollen right on the pistol of that same flower, 91 00:06:40 --> 00:06:45 which is a kind of self fertilization, 92 00:06:45 --> 00:06:50 or to make sure that the pollen goes from one flower to another, 93 00:06:50 --> 00:06:55 which is basically cross-pollination. And the third thing, 94 00:06:55 --> 00:07:00 and this was a really important thing, was the system had worked on 95 00:07:00 --> 00:07:05 before. And there were a number of what were called pure 96 00:07:05 --> 00:07:09 breeding lines. If he had just grabbed peas out of 97 00:07:09 --> 00:07:12 the wild it would be sort of like me starting to do genetics by crossing 98 00:07:12 --> 00:07:16 a couple of you guys. We'd get offspring, all right, 99 00:07:16 --> 00:07:19 and we'd cross those offspring, we'd keep getting things, 100 00:07:19 --> 00:07:22 people that look different and different, maybe something like the 101 00:07:22 --> 00:07:26 parents, but what had happened with peas is people had taken a pea, 102 00:07:26 --> 00:07:29 and then they continually inbred it until it finally sort of settled 103 00:07:29 --> 00:07:33 down. It always had white flowers. 104 00:07:33 --> 00:07:36 It always had wrinkled seeds. It always had whatever the 105 00:07:36 --> 00:07:39 particular trait was. And so, I think I showed you the 106 00:07:39 --> 00:07:43 slide earlier. This shows two things. 107 00:07:43 --> 00:07:46 You can see there are smooth seeds and then wrinkled seeds. 108 00:07:46 --> 00:07:50 And it may be a little hard to tell in this light, 109 00:07:50 --> 00:07:53 but there is sort of two colors here. One's kind of greenish and one's 110 00:07:53 --> 00:07:57 sort of yellowish. So there, you see two of the traits 111 00:07:57 --> 00:08:00 right there. There were also flower colors, and height, 112 00:08:00 --> 00:08:04 and other things that had the characteristic. 113 00:08:04 --> 00:08:09 They were pure breeding. Every time you took that line and 114 00:08:09 --> 00:08:14 if you self crossed it and put out its progeny, you'd see the same 115 00:08:14 --> 00:08:19 characteristic each time. So, this was the system that Mendel 116 00:08:19 --> 00:08:25 started to study this problem of inheritance. And how does blending 117 00:08:25 --> 00:08:30 come together when two organisms brought pollen? 118 00:08:30 --> 00:08:36 Or, if it was other animals like us, it would be sperm and egg. 119 00:08:36 --> 00:08:40 But somehow, you did something that ended up giving you an egg that got 120 00:08:40 --> 00:08:45 fertilized. And out of that came the progeny. So, 121 00:08:45 --> 00:08:50 what Mendel did, the term that's used, they say he carried out a 122 00:08:50 --> 00:08:55 cross. This is genetic-speak here now. So he took pollen 123 00:08:55 --> 00:09:09 from one plant. 124 00:09:09 --> 00:09:16 And used it to fertilize another plant, collected the seeds that came 125 00:09:16 --> 00:09:23 out of this, and he examined the progeny. And I think an interesting 126 00:09:23 --> 00:09:31 way of thinking about this is a UROP project. 127 00:09:31 --> 00:09:35 You'd come into Mendel's lab and wanted to do a UROP project, 128 00:09:35 --> 00:09:39 it was pretty easy. I could probably show you all the techniques 129 00:09:39 --> 00:09:43 you needed to know, and this is it. You'd show how you 130 00:09:43 --> 00:09:47 pollinate, collect seeds, and then we'd look at the 131 00:09:47 --> 00:09:51 characteristics. So, it's just some fairly simple 132 00:09:51 --> 00:09:55 manipulations and some observational stuff. So, let's suppose you're 133 00:09:55 --> 00:09:59 doing Mendel's thing as a UROP project, and let's just see where 134 00:09:59 --> 00:10:05 that will take us. So, what Mendel did to begin with, 135 00:10:05 --> 00:10:11 he took one of these pure breeding lines that was smooth or all 136 00:10:11 --> 00:10:17 abbreviated as a capital S. And he pollinated it with something 137 00:10:17 --> 00:10:24 that was wrinkled. I'll do that as little S. 138 00:10:24 --> 00:10:30 And then he collected the seeds from what's known as the first 139 00:10:30 --> 00:10:37 generation, starting with something like this. 140 00:10:37 --> 00:10:45 And geneticists use the term F1 for this first generation in a cross 141 00:10:45 --> 00:10:54 like this, and what he found was everything, all the seeds, 142 00:10:54 --> 00:11:03 were smooth. So, the wrinkled trait had, if you will, disappeared. 143 00:11:03 --> 00:11:19 That's your first UROP experiment. 144 00:11:19 --> 00:11:24 [Time doesn't?] submit to nature, or science, or something, 145 00:11:24 --> 00:11:30 and read a little paper like Watson and Craig that turns the world on 146 00:11:30 --> 00:11:36 its end. What would you do next? No gels, no Whitehead Sequencing 147 00:11:36 --> 00:11:42 Facility. Anybody got any ideas? I've showed you all the techniques 148 00:11:42 --> 00:11:49 that he knew about. Pardon? Cross it again? 149 00:11:49 --> 00:11:55 What's your thinking? Do you think the traits disappear, 150 00:11:55 --> 00:12:02 or do you think it's hiding? It might be hiding, right? 151 00:12:02 --> 00:12:08 I don't know what he thought, but I think that's a reasonable to 152 00:12:08 --> 00:12:14 think about it is he's probably trying to figure out, 153 00:12:14 --> 00:12:20 did this wrinkled trait just disappear from the face of the Earth, 154 00:12:20 --> 00:12:26 or is it hiding in those first-generation seeds? 155 00:12:26 --> 00:12:33 So, let's put that up here. So, that's exactly what he did. 156 00:12:33 --> 00:12:39 So, he took these seeds, now, that were the smooth F1. 157 00:12:39 --> 00:12:45 These are not the same smooth as the parental up here. 158 00:12:45 --> 00:12:51 Just to make clear, you guys understand these are pure breeding. 159 00:12:51 --> 00:12:57 These are the ones that people have been breeding for a long time, 160 00:12:57 --> 00:13:03 this one and this one. In this case, even though I'm trying 161 00:13:03 --> 00:13:10 it in circles, this is a smooth F1, 162 00:13:10 --> 00:13:17 smooth F1. And, this time when he did the experiment he looked at the 163 00:13:17 --> 00:13:24 second generation, or the F2 generation as a geneticist 164 00:13:24 --> 00:13:31 would call it. What he found, 165 00:13:31 --> 00:13:38 he got some smooth and he got some wrinkled. 166 00:13:38 --> 00:13:52 So, the wrinkled trait reemerged in the F2. So it wasn't really gone. 167 00:13:52 --> 00:14:03 It was hiding. OK, time to submit to nature's 168 00:14:03 --> 00:14:09 science cell. Got it? He didn't try and publish it at 169 00:14:09 --> 00:14:15 that point. He did something else. He had the same kind of background 170 00:14:15 --> 00:14:21 you guys have. Can he think what he might've done? 171 00:14:21 --> 00:14:27 He could cross again. There's something else he did with this 172 00:14:27 --> 00:14:33 experiment, though. Well, you're thinking of new 173 00:14:33 --> 00:14:40 experiments. He's got a little data processing he 174 00:14:40 --> 00:14:46 can do here. What did you say? I'm not able to hear, sorry. 175 00:14:46 --> 00:14:52 Statistics, OK. I'll simplify it even slightly 176 00:14:52 --> 00:14:58 before that. I've got some of each. Count them, right, exactly. So 177 00:14:58 --> 00:15:04 that's what he did, and I think the numbers were, 178 00:15:04 --> 00:15:11 if I remember, five, four, seven, four in 1850. 179 00:15:11 --> 00:15:15 So, what should I do now? Ratio: absolutely. We could count 180 00:15:15 --> 00:15:19 another million of them, but that probably would not be 181 00:15:19 --> 00:15:23 terribly productive. And what he found out is that when 182 00:15:23 --> 00:15:27 he did that, he found that he got a ratio that was pretty 183 00:15:27 --> 00:15:35 close to 3:1. And, so that was sort of what he 184 00:15:35 --> 00:15:46 found out from this by doing this sort of thing over again was a 185 00:15:46 --> 00:15:58 pattern. A trait disappeared in the F1. The trait reemerged in the F2, 186 00:15:58 --> 00:16:07 and the two traits had this. The ratio of the two traits would be 187 00:16:07 --> 00:16:13 about 3:1. If you don't think this is sort of like a UROP project or 188 00:16:13 --> 00:16:20 something, that's a page out of some of Mendel's actual notes while he 189 00:16:20 --> 00:16:26 was doing his crosses. And what he did next, then, 190 00:16:26 --> 00:16:32 was to take some other traits. Yeah? Sorry? Excuse me? 191 00:16:32 --> 00:16:36 Reemerged in F2. So, he took some other traits, white and purple 192 00:16:36 --> 00:16:41 flowers, tall, short, I found that there were at 193 00:16:41 --> 00:16:45 least certain other traits. It didn't work for everything he 194 00:16:45 --> 00:16:50 studied, but some of them he could see the same pattern. 195 00:16:50 --> 00:16:54 One of the traits disappeared. It reemerged in the F2, and when he 196 00:16:54 --> 00:16:59 counted them, he'd find that the trait that reemerged was at one, 197 00:16:59 --> 00:17:04 and the other one there were three times as many. 198 00:17:04 --> 00:17:08 So, he'd seen a pattern. And all he's done at this point is 199 00:17:08 --> 00:17:13 to cross flowers and count the progeny. So, at that point Mendel 200 00:17:13 --> 00:17:17 tried to explain his data. So, he had to, now, take the next 201 00:17:17 --> 00:17:22 part of the scientific process. And what's kind of nice about 202 00:17:22 --> 00:17:27 thinking about Mendel, in this sense, is we are not 203 00:17:27 --> 00:17:32 overwhelmed by complicated techniques. 204 00:17:32 --> 00:17:35 You can see, I think, the scientific process. 205 00:17:35 --> 00:17:38 And it's a very bare bones thing marching along. 206 00:17:38 --> 00:17:41 So now he's got some data. He's quantitated his stuff. 207 00:17:41 --> 00:17:44 He's founded reproducible. It's not only for seeds. 208 00:17:44 --> 00:17:47 It seems to be some general feature. And the thing about this, 209 00:17:47 --> 00:17:51 I guess, I don't know what he thought but it seems to be likely 210 00:17:51 --> 00:17:54 that he could see that this didn't fit very well with the blending idea. 211 00:17:54 --> 00:17:57 Like, you'd pour together two liquids, and you'd 212 00:17:57 --> 00:18:01 stir them all up. Instead, he really made this 213 00:18:01 --> 00:18:05 monumental leap in thinking that genetic information must come in 214 00:18:05 --> 00:18:09 some sort of particular form, come in particles, or units, or 215 00:18:09 --> 00:18:14 quanta if you want to think about if it if you're a physicist. 216 00:18:14 --> 00:18:18 We know those units as genes right now. We grow up with it right now, 217 00:18:18 --> 00:18:22 but to go from the idea that genetic information was kind of like two 218 00:18:22 --> 00:18:27 liquids blending to the idea it was a little particle, 219 00:18:27 --> 00:18:31 so it was just about the same kind of leap as thinking that energy 220 00:18:31 --> 00:18:36 comes in particles instead of a continuous sort of thing. 221 00:18:36 --> 00:18:48 So, that was the kind of insight that Mendel had. 222 00:18:48 --> 00:19:00 And so genetic info comes in particles, units. 223 00:19:00 --> 00:19:05 I was going to say, we now call these genes, 224 00:19:05 --> 00:19:11 and if that was what it was then he started to think about these traits 225 00:19:11 --> 00:19:16 as particles that had a different character associated with each of 226 00:19:16 --> 00:19:22 them. That would mean there would be one particle that was a big S, 227 00:19:22 --> 00:19:28 and that was smooth. There was some other particle that was specified. 228 00:19:28 --> 00:19:34 The wrinkled character, that would be called a small s. 229 00:19:34 --> 00:19:38 So, what was happening in these crosses, then, 230 00:19:38 --> 00:19:42 he was now mixing particles instead of liquids. Again, 231 00:19:42 --> 00:19:46 I don't know how he got to, how many particles there had to be 232 00:19:46 --> 00:19:50 of each per organism. It could have been anywhere from 233 00:19:50 --> 00:19:54 two upwards. He had to have two in order to explain the sort of stuff 234 00:19:54 --> 00:19:58 he was working with. There's no reason he couldn't have 235 00:19:58 --> 00:20:03 thought of 12 or something. But I assume you start with the very 236 00:20:03 --> 00:20:11 simplest thing, number that you can think of, 237 00:20:11 --> 00:20:18 and see if you can make this work. So, what he hypothesized, then, was 238 00:20:18 --> 00:20:26 that each organism had two copies of each of these particles. 239 00:20:26 --> 00:20:34 So, two copies of each particle, so this would mean that there were 240 00:20:34 --> 00:20:41 two types of particles. So, there would be the S and the 241 00:20:41 --> 00:20:48 smooth. So, he can get three types of things. He could get one that 242 00:20:48 --> 00:20:55 was both big S or smooth. Or you could have the ones that 243 00:20:55 --> 00:21:03 were the two little S's. And these would be wrinkled. 244 00:21:03 --> 00:21:09 Or, if you had the other combination, what he figured out, 245 00:21:09 --> 00:21:15 what fit with this model is these would have to be smooth. 246 00:21:15 --> 00:21:21 That would have to mean that one of them is dominant over the other when 247 00:21:21 --> 00:21:27 you put them in combination. So, in this thing, the big S would 248 00:21:27 --> 00:21:32 be said to be dominant. And the little s Would be said to be 249 00:21:32 --> 00:21:38 recessive. There's another little term here that I'm going to 250 00:21:38 --> 00:21:43 introduce because it'll help us talk about this stuff over the next few 251 00:21:43 --> 00:21:49 days, terms geneticists use all the time. Because these both have two 252 00:21:49 --> 00:21:54 of the same, they're said to be homozygous, do the same. 253 00:21:54 --> 00:22:00 And this one, with one of each, is said to be heterozygous. 254 00:22:00 --> 00:22:04 OK, so there is, I think, sort of the setup for 255 00:22:04 --> 00:22:09 Mendel's model. He had to contend with one other 256 00:22:09 --> 00:22:14 issue, though, and that was if every organism has 257 00:22:14 --> 00:22:19 two, and two parents get together and each donate something, 258 00:22:19 --> 00:22:24 unless you did something, the offspring would have four. 259 00:22:24 --> 00:22:29 When those offspring got together, the next one would have twice as 260 00:22:29 --> 00:22:34 many, and so on. So, from probably, 261 00:22:34 --> 00:22:39 I don't know whether it was just from first principle, 262 00:22:39 --> 00:22:43 but I would imagine he figured out that if organisms had sex with 263 00:22:43 --> 00:22:48 pollen and whatever, or egg and sperm, that something had 264 00:22:48 --> 00:22:53 to be done to get around this problem of an ever increasing number 265 00:22:53 --> 00:22:57 of particles. So, he envisioned that when there were 266 00:22:57 --> 00:23:02 specialized cells for sex, and that they have the number so 267 00:23:02 --> 00:23:07 that the sex cells would have half the number of particles so that when 268 00:23:07 --> 00:23:12 each parent donated one, you'd be back up to two. 269 00:23:12 --> 00:23:18 It's pretty simple, straightforward thinking once you've 270 00:23:18 --> 00:23:24 gotten the idea that these things are coming in a particular form. 271 00:23:24 --> 00:23:30 So, with this, could he now explain his results? 272 00:23:30 --> 00:23:37 Let's do it over here. So, what happened in the first 273 00:23:37 --> 00:23:45 cross? He had a smooth, pure breeding line crossed with, 274 00:23:45 --> 00:23:52 so the sex cells from this, each one would have been a big S, 275 00:23:52 --> 00:24:00 and the sex cells from each one of this would have been a little s. 276 00:24:00 --> 00:24:08 And as you recall, what he got was all smooth, right? Remember? 277 00:24:08 --> 00:24:13 So, if we try and figure out what's happening here, 278 00:24:13 --> 00:24:19 a way of representing this would be to think what happens if all of the 279 00:24:19 --> 00:24:25 combinations that you could get, so if we paired them in all possible 280 00:24:25 --> 00:24:31 ways, then every combination would be identical from that first cross, 281 00:24:31 --> 00:24:37 one from one parent, one from the other. 282 00:24:37 --> 00:24:41 And, if one was dominant over the other, it's going to look like this. 283 00:24:41 --> 00:24:46 This is really the word I introduced you to. 284 00:24:46 --> 00:24:50 That's the genotype. That's what's going on down at the 285 00:24:50 --> 00:24:55 genetic level. What you're seeing up here is the 286 00:24:55 --> 00:25:00 observable characteristics of the organism. 287 00:25:00 --> 00:25:06 That would be the phenotype. So, then what would happen then 288 00:25:06 --> 00:25:13 with this if he crossed the F1's? Well, as you recall, they were 289 00:25:13 --> 00:25:20 smooth, but he was now seeing them as being like this. 290 00:25:20 --> 00:25:27 So that means that the sex cells that are generated from this, 291 00:25:27 --> 00:25:34 each one will generate one big S, and one little s. 292 00:25:34 --> 00:25:42 And then, if you put them together to see how this would work out, 293 00:25:42 --> 00:25:51 well, this one's two big S's. This is a big S and a little s, 294 00:25:51 --> 00:26:00 a big S and a little s, and two little s's. So, 295 00:26:00 --> 00:26:09 what he's got over here is SS, SS, and a ratio of 1:2:1. 296 00:26:09 --> 00:26:14 But when you look at the phenotype, what would we expect? Well, this 297 00:26:14 --> 00:26:19 would be smooth, big S and little s. 298 00:26:19 --> 00:26:24 That's smooth. Big S, little s, smooth again, and two 299 00:26:24 --> 00:26:31 little s's, that's wrinkled. There's his ratio of 3:1. 300 00:26:31 --> 00:26:41 Has he proved anything? It works. Beautiful. The model must be right? 301 00:26:41 --> 00:26:50 What do you think? Are you ready to publish? 302 00:26:50 --> 00:27:00 Why is that? Why did the model work? 303 00:27:00 --> 00:27:04 Has the model predicted anything yet? No, it works because it describes 304 00:27:04 --> 00:27:08 the data. To some extent, it's kind of like hitting a curve. 305 00:27:08 --> 00:27:12 You said it, but you don't really know yet. Of course it's going to 306 00:27:12 --> 00:27:16 work, because if you got different data it would've had a different 307 00:27:16 --> 00:27:20 model. So, you're putting your finger on a really important point, 308 00:27:20 --> 00:27:24 and that is that you can do an experiment. You can get data. 309 00:27:24 --> 00:27:28 It doesn't have to involve DNA sequencing or fancy technique. 310 00:27:28 --> 00:27:33 You're getting data out of a biological system. 311 00:27:33 --> 00:27:37 You've come up with a hypothesis that explains it. 312 00:27:37 --> 00:27:41 But of course it's going to explain it because you wouldn't publish a 313 00:27:41 --> 00:27:46 model that didn't explain your own data. But what he hasn't done is 314 00:27:46 --> 00:27:50 tested it. Will his model predict the outcome of something that he 315 00:27:50 --> 00:27:55 hasn't already done? So, the suggestion was that he 316 00:27:55 --> 00:27:59 should carry out another cross. And that's what Mendel then did 317 00:27:59 --> 00:28:05 again. This is what he had to work with. 318 00:28:05 --> 00:28:11 He could cross, and he could count, and he could do some calculating and 319 00:28:11 --> 00:28:18 some thinking. But, those were the techniques. 320 00:28:18 --> 00:28:24 I really like thinking about this, because you can sort of put yourself 321 00:28:24 --> 00:28:31 in his shoes. So, what would you guys like to cross? 322 00:28:31 --> 00:28:37 We haven't got much, right? One, he did. One cross he did, 323 00:28:37 --> 00:28:44 the F1 with the homozygous dominant parent, the pure breeding lines. 324 00:28:44 --> 00:28:51 So, he's got this smooth, that's a big S and a little s, 325 00:28:51 --> 00:28:58 and he's crossing it with something, two big S's. So, the sex cells that 326 00:28:58 --> 00:29:05 you'll get out of this, so if you set this one up and see 327 00:29:05 --> 00:29:11 what happens, there's the two. You will get to big S's, 328 00:29:11 --> 00:29:16 big S, little S, the big S, little S. This is sort of 329 00:29:16 --> 00:29:22 uninformative. If you want to look at your notes 330 00:29:22 --> 00:29:27 afterwards, and have this be consistent, let me just 331 00:29:27 --> 00:29:32 flip this slightly. I put the two big S's up here, 332 00:29:32 --> 00:29:37 and this is our F1 down here. That way I'll be following the same 333 00:29:37 --> 00:29:42 pattern as I did before. OK, so there we are. In any case, 334 00:29:42 --> 00:29:47 they're all smooth, but that's not particularly helpful. 335 00:29:47 --> 00:29:52 He's seen that result before. It hasn't really proven out. Given 336 00:29:52 --> 00:29:57 the sort of unexpected result that's predicted by his model. 337 00:29:57 --> 00:30:03 But he tried another one that's very, very similar. 338 00:30:03 --> 00:30:15 And in this case, he crossed the F1 with the 339 00:30:15 --> 00:30:27 homozygous recessive parent. This is a really important process 340 00:30:27 --> 00:30:35 in genetics. And the reason, 341 00:30:35 --> 00:30:41 because it's so important, it's given a special term that's 342 00:30:41 --> 00:30:47 called a test cross. Let's see what happens with this 343 00:30:47 --> 00:30:53 one, because this one's more interesting. So, 344 00:30:53 --> 00:30:59 we take the F1. So, this is the F1. He's now crossing 345 00:30:59 --> 00:31:05 it with this homozygous recessive, so a parent that's got two particles 346 00:31:05 --> 00:31:11 that are little s. And so, will the sex cells look like 347 00:31:11 --> 00:31:17 this, a big S little s as before, to little S's here? So, if we set 348 00:31:17 --> 00:31:23 up this, as we've done, there are the sex cells from this F1. 349 00:31:23 --> 00:31:29 Here are the sex cells from the homozygous, recessive parent. 350 00:31:29 --> 00:31:35 Up here, we get a big S and a little s for each of those. 351 00:31:35 --> 00:31:40 But here, we get two little s's. So, if we look at the phenotype, 352 00:31:40 --> 00:31:46 if you're out on the field or out in the garden sitting in the kitchen, 353 00:31:46 --> 00:31:52 after you brought your seeds in or wherever he was working, 354 00:31:52 --> 00:31:58 what would you predict you'd see in a cross like this? 355 00:31:58 --> 00:32:04 These would be both smooth, but these would both be wrinkled. 356 00:32:04 --> 00:32:09 So, here at the genotypic level, we've got a ratio, now, of 1:1. And 357 00:32:09 --> 00:32:15 here as well, there's now a ratio of 1:1. So, there you have a result 358 00:32:15 --> 00:32:21 that you haven't seen before. And, if you do that cross and get 359 00:32:21 --> 00:32:27 that result, again, it doesn't prove your model. 360 00:32:27 --> 00:32:33 Scientific proof is never a QED. 361 00:32:33 --> 00:32:37 Somebody can always come up with an experiment tomorrow that disproves 362 00:32:37 --> 00:32:42 it. It tends to work more. You just keep shoveling on evidence, 363 00:32:42 --> 00:32:47 and finally someone says, enough, enough, I believe you. 364 00:32:47 --> 00:32:52 So, this was at least a test of the model, and the model survived this 365 00:32:52 --> 00:32:56 task. Now, he did one other experiment. Of the things that 366 00:32:56 --> 00:33:01 we've got on our plate right now, is there anything else we might do 367 00:33:01 --> 00:33:08 you can think of? He did another cross. 368 00:33:08 --> 00:33:16 Pardon? Two of the heterogeneous ones, we did the F1's against each 369 00:33:16 --> 00:33:24 other. That's where we got the 3:1. We've already crossed the F1's, but 370 00:33:24 --> 00:33:33 I like your idea. What if we took the F2's? 371 00:33:33 --> 00:33:37 In this case, it's going to be pretty complicated because they've 372 00:33:37 --> 00:33:42 got this 2:1:1, but one of the things you can do 373 00:33:42 --> 00:33:46 with peas is you can self fertilize them as well as cross them with 374 00:33:46 --> 00:33:51 their neighbors because they've got the ability to make the eggs. 375 00:33:51 --> 00:33:55 It'll become the seeds, and they have the pollen, 376 00:33:55 --> 00:34:00 which would be equivalent to the sperm. So it got both. 377 00:34:00 --> 00:34:06 So, as long as there's some plants that you can self fertilize and some 378 00:34:06 --> 00:34:12 you can't, one of the really nice things about peas, 379 00:34:12 --> 00:34:19 they have the property that you can self fertilize them. 380 00:34:19 --> 00:34:25 So, another kind of experiment that Mendel did, then, 381 00:34:25 --> 00:34:32 was to self fertilize another test of the model, self fertilize the 382 00:34:32 --> 00:34:38 F2's. Well, the model predicts, if we look back over there, that 383 00:34:38 --> 00:34:45 what you'll have there is a mix of things in a ratio of 1:2:1. 384 00:34:45 --> 00:34:49 So, if you were to take seeds from that F2, and then cross them with 385 00:34:49 --> 00:34:53 themselves, you could figure out all the different outcomes, 386 00:34:53 --> 00:34:57 and then sum them up. You'd have a prediction for what this 387 00:34:57 --> 00:35:02 model would suggest. All right, so let me just take you 388 00:35:02 --> 00:35:08 through the pieces. Let's think about a quarter of them, 389 00:35:08 --> 00:35:14 according to the model, a quarter are that. So, 390 00:35:14 --> 00:35:19 if we self cross those, what we should get is all wrinkled because 391 00:35:19 --> 00:35:25 the only thing we're dealing with is the wrinkled trait. 392 00:35:25 --> 00:35:31 So, that would be a quarter of the F2 seeds would be expected 393 00:35:31 --> 00:35:39 to give that outcome. So, three quarters of them are 394 00:35:39 --> 00:35:51 smooth, but it's tricky because there's two types of them in there, 395 00:35:51 --> 00:36:03 right? So, of these, one third are this, and two thirds have that. 396 00:36:03 --> 00:36:09 So, what would happen if we thought about each of those individually, 397 00:36:09 --> 00:36:15 and thought about the outcome? Well, if we take the SS type, 398 00:36:15 --> 00:36:21 and we've self crossed them, what we're going to get is all 399 00:36:21 --> 00:36:27 smooth because all we've got in the cross are the traits for the smooth 400 00:36:27 --> 00:36:33 characteristic. And, if we take these guys and 401 00:36:33 --> 00:36:39 we've self-crossed them, we've already done that. 402 00:36:39 --> 00:36:46 We know what we will get is we will get smooth to wrinkled in a ratio of 403 00:36:46 --> 00:36:54 3:1. So, again, you could now sit down with that and 404 00:36:54 --> 00:37:01 figure out in total what you would predict in terms of smooth and 405 00:37:01 --> 00:37:09 wrinkled if you self crossed the F2, and if the model is correct. 406 00:37:09 --> 00:37:14 So, that was basically [your? first UROP project, or the end of 407 00:37:14 --> 00:37:20 the first term, or the first year, 408 00:37:20 --> 00:37:25 or something like that. And he did publish those results 409 00:37:25 --> 00:37:31 that were published in 1866, which was the same year as those, 410 00:37:31 --> 00:37:37 about the same time as those results that Pasteur was publishing that I 411 00:37:37 --> 00:37:43 told you about earlier on. So, it was a very impressive in 412 00:37:43 --> 00:37:49 retrospect, a truly major intellectual leap. 413 00:37:49 --> 00:37:56 But, it had almost no impact at all on the world. And there's a theme 414 00:37:56 --> 00:38:03 here that it sort of tried to hit up several times. 415 00:38:03 --> 00:38:06 And we saw it, to some extent, 416 00:38:06 --> 00:38:10 with the early work on DNA, that someone can get evidence for an 417 00:38:10 --> 00:38:14 idea. But if the scientific community is ready to accept it, 418 00:38:14 --> 00:38:18 it can take quite awhile before that idea becomes credible even if it's 419 00:38:18 --> 00:38:22 correct. The data was there. The DNA was genetic material quite 420 00:38:22 --> 00:38:26 a bit before the general scientists thought it was, 421 00:38:26 --> 00:38:30 and it just seemed like it was too simple a molecule, 422 00:38:30 --> 00:38:34 too boring a molecule to be possibly able to encode anything. 423 00:38:34 --> 00:38:38 And the same sort of thing happened here. It was some geneticists 424 00:38:38 --> 00:38:41 picked up on this but not until about 1900.