1 00:00:18 --> 00:00:24 OK. Let's get started. We're going to complete our 2 00:00:24 --> 00:00:30 discussion about mitosis and meiosis today. 3 00:00:30 --> 00:00:35 And then get into a topic called Mendelian Genetics, 4 00:00:35 --> 00:00:40 understanding genetic principles. And we'll give you as examples the 5 00:00:40 --> 00:00:46 work of the famous Austrian monk Gregor Mendel who sort of set down 6 00:00:46 --> 00:00:51 the rules that we still follow today regarding simple genetic inheritance. 7 00:00:51 --> 00:00:57 So I mentioned to you last time, and I think you all know that your 8 00:00:57 --> 00:01:01 genes are carried on chromosomes. And chromosomes come in different 9 00:01:01 --> 00:01:05 sizes and shapes. You have 46 total chromosomes in 10 00:01:05 --> 00:01:09 all of your cells. Those chromosomes come from your 11 00:01:09 --> 00:01:13 parents. You get one set from one parent and another set from another 12 00:01:13 --> 00:01:17 parent, so you have 22 pairs plus the two sex chromosomes. 13 00:01:17 --> 00:01:21 And the chromosomes are made of DNA, and along those DNA sequences are 14 00:01:21 --> 00:01:25 your genes scattered along the length of the chromosomes. 15 00:01:25 --> 00:01:29 And there are about 30,000 genes in total. 16 00:01:29 --> 00:01:33 Now, I've also told you that the genome, the whole sequence of your 17 00:01:33 --> 00:01:37 DNA has been determined over the last couple of years. 18 00:01:37 --> 00:01:42 We now know that in great detail. We know every single nucleotide of 19 00:01:42 --> 00:01:46 the three times ten to the ninth base pairs of DNA, 20 00:01:46 --> 00:01:51 and we can actually go to a website and look at it. 21 00:01:51 --> 00:01:55 You can do this. It's publicly available, 22 00:01:55 --> 00:01:59 sponsored by the government, but it's a little like hacking into 23 00:01:59 --> 00:02:04 the database of humanity. So if you go to this website that I 24 00:02:04 --> 00:02:08 just showed you, you'll find access to the genomes of 25 00:02:08 --> 00:02:12 many organisms. This is an evolutionary tree which 26 00:02:12 --> 00:02:17 shows the relationship of these organisms from an evolutionary 27 00:02:17 --> 00:02:21 perspective. There are nine mammalian genomes that are present 28 00:02:21 --> 00:02:25 within this database. If you clink on that link to 29 00:02:25 --> 00:02:30 homosapiens, that's us, assuming this is functioning. 30 00:02:30 --> 00:02:34 I had this working. I'm not sure why it's not working. 31 00:02:34 --> 00:02:38 I'm getting a good signal here. Oh well. Had this worked, 32 00:02:38 --> 00:02:42 you would have seen an alignment, a diagram of all the human 33 00:02:42 --> 00:02:47 chromosomes, one through 22, plus X plus Y. You could then click 34 00:02:47 --> 00:02:51 on chromosome whatever you're interested, let's say chromosome one. 35 00:02:51 --> 00:02:55 It would show a diagram of chromosome one from end to end. 36 00:02:55 --> 00:03:00 And you could then click on the sequence of chromosome one. 37 00:03:00 --> 00:03:04 All two point four times ten to the eighth base pairs of chromosome one. 38 00:03:04 --> 00:03:08 It would show you all of the genes on chromosomes one. 39 00:03:08 --> 00:03:12 You would know exactly where they were. And you could then click on a 40 00:03:12 --> 00:03:17 particular gene and look at its sequence. And it would actually 41 00:03:17 --> 00:03:21 give you information about that gene, as much information as is known. 42 00:03:21 --> 00:03:25 So, we know the nucleotide sequence of all the genes. 43 00:03:25 --> 00:03:29 And the question is, is that sequence that's in that 44 00:03:29 --> 00:03:34 database applicable to all of you? Is that the sequence of your DNA? 45 00:03:34 --> 00:03:40 What do you say? Why do you say no? Right. So it's somebody's DNA. 46 00:03:40 --> 00:03:46 Actually, the genome sequence that's present in a publicly 47 00:03:46 --> 00:03:51 available database is a collection of a small number of people's DNA, 48 00:03:51 --> 00:03:57 but it's a representation of the human genome. And you all have 49 00:03:57 --> 00:04:02 subtle differences. In between genes quite a few, 50 00:04:02 --> 00:04:06 and within your genes some. And we call those differences within genes 51 00:04:06 --> 00:04:10 allelic differences, you have different alleles, 52 00:04:10 --> 00:04:14 and that's what makes you all different, which alleles you carry, 53 00:04:14 --> 00:04:18 and importantly which combinations of alleles of genes that you carry. 54 00:04:18 --> 00:04:22 OK. I apologize for that not working. I don't know why it didn't. 55 00:04:22 --> 00:04:26 All right. Well, last time we left off talking about 56 00:04:26 --> 00:04:30 the fact that you inherit your chromosomes through the process 57 00:04:30 --> 00:04:34 of fertilization. Fusion of sperm and egg produces a 58 00:04:34 --> 00:04:38 diploid cell from two haploid cells. This diploid cell has two copies of 59 00:04:38 --> 00:04:42 all the chromosomes, two copies of all the genes, 60 00:04:42 --> 00:04:46 and then through the process of development there is a great deal of 61 00:04:46 --> 00:04:50 mitosis. We talked about mitosis in some detail last time. 62 00:04:50 --> 00:04:54 The process of chromosome duplication followed by chromosome 63 00:04:54 --> 00:04:58 separation, chromatid separation really, which allows daughter cells, 64 00:04:58 --> 00:05:02 during this process of mitosis to faithfully inherit all of the DNA. 65 00:05:02 --> 00:05:05 And this process continues through development, and it also continues 66 00:05:05 --> 00:05:08 in adults. It's not over when the baby is born. There's a lot of 67 00:05:08 --> 00:05:11 mitosis that takes place in many of your organs, and your intestines for 68 00:05:11 --> 00:05:15 example, your blood. Not in all of your organs. 69 00:05:15 --> 00:05:18 In the brain, for example, there is relatively little mitosis. 70 00:05:18 --> 00:05:21 Once the brain forms, cells don't divide anymore. 71 00:05:21 --> 00:05:25 It's true of the cardiac muscle as well in the heart. 72 00:05:25 --> 00:05:28 But many tissues do continue to divide. So this is happening inside 73 00:05:28 --> 00:05:31 of you as we speak. Now, what I want to turn to for 74 00:05:31 --> 00:05:35 today, though, is to talk about this process. 75 00:05:35 --> 00:05:38 How do you go back to the beginning? How do you generate haploid cells 76 00:05:38 --> 00:05:42 from diploid cells? And this occurs through a related 77 00:05:42 --> 00:05:46 process called meiosis. Now, meiosis takes place at 78 00:05:46 --> 00:05:49 different times, depending on whether you're male or 79 00:05:49 --> 00:05:53 female. As I mentioned last time in males meiosis takes place 80 00:05:53 --> 00:05:56 in puberty. So diploid germ cells are set aside 81 00:05:56 --> 00:06:00 in embryogenesis, but they don't undergo this process 82 00:06:00 --> 00:06:04 of meiosis until males reach puberty at which point it happens very 83 00:06:04 --> 00:06:07 abundantly, as I said, about a million or a couple of 84 00:06:07 --> 00:06:11 million meiotic cells produced per hour. In females meiosis actually 85 00:06:11 --> 00:06:15 begins in embryogenesis, quite amazing. The cells are set 86 00:06:15 --> 00:06:18 aside and they start to undergo meiosis. And they don't make it all 87 00:06:18 --> 00:06:22 the way through. You don't make haploid germ cells 88 00:06:22 --> 00:06:26 in embryogenesis. They get stuck partway through. 89 00:06:26 --> 00:06:30 Then in puberty, during ovulation a subset of those 90 00:06:30 --> 00:06:34 cells continue through the subsequent stages of meiosis. 91 00:06:34 --> 00:06:38 Then they get stuck again. And only at fertilization does meiosis 92 00:06:38 --> 00:06:42 get completed, a haploid cell is produced which is 93 00:06:42 --> 00:06:46 then fused with the sperm cell, a diploid cell is generated and 94 00:06:46 --> 00:06:50 development proceeds. So what is meiosis and how does it 95 00:06:50 --> 00:07:04 compare to mitosis? 96 00:07:04 --> 00:07:11 Well, they're related in the sense that both of them follow S phase. 97 00:07:11 --> 00:07:19 If you remember during S phase chromosomes get duplicated. 98 00:07:19 --> 00:07:27 And during chromosome duplication two chromatids are produced. 99 00:07:27 --> 00:07:38 You're not going to start singing, 100 00:07:38 --> 00:07:46 are you? No. Just kidding. When a chromosome gets produced two 101 00:07:46 --> 00:07:53 chromatids are generated and then they stick together at the 102 00:07:53 --> 00:08:01 centromere. Remember that? Now, in mitosis, as we talked about 103 00:08:01 --> 00:08:09 before, this is followed by one round of chromatid separation. 104 00:08:09 --> 00:08:12 That's all it is. The chromosomes with their two 105 00:08:12 --> 00:08:16 chromatids line up along the metaphase plate, 106 00:08:16 --> 00:08:20 and they get pulled apart during anaphase and telophase. 107 00:08:20 --> 00:08:24 And importantly the homologs don't pay any attention to one another. 108 00:08:24 --> 00:08:28 The maternal copy of chromosome one and the paternal copy of chromosome 109 00:08:28 --> 00:08:31 two ignore each other in mitosis. They could be anywhere along that 110 00:08:31 --> 00:08:34 metaphase plate. It doesn't matter. 111 00:08:34 --> 00:08:37 They ignore one another. OK? That's relevant because it's 112 00:08:37 --> 00:08:45 different in meiosis. 113 00:08:45 --> 00:08:54 In meiosis, also following one round of chromosome duplication and the 114 00:08:54 --> 00:09:04 generation of two chromatids per chromosome, this involves one round 115 00:09:04 --> 00:09:11 of chromosome separation. And when I say chromosome here, 116 00:09:11 --> 00:09:16 I'm talking about the chromosome which is at this point composed of 117 00:09:16 --> 00:09:22 two chromatids. In this case the homologs do pay 118 00:09:22 --> 00:09:27 attention to one another and they separate from one another. 119 00:09:27 --> 00:09:33 Followed by one round of chromatid separation. 120 00:09:33 --> 00:09:37 Which is very similar to what happens over here. 121 00:09:37 --> 00:09:41 OK? So the way you go from having 46 chromosomes to 23 chromosomes is 122 00:09:41 --> 00:09:45 you go through one round of duplication but two rounds of 123 00:09:45 --> 00:09:50 separation. The way you maintain 46 chromosomes in mitosis is to go 124 00:09:50 --> 00:09:54 through one round of duplication and only one round of separation. 125 00:09:54 --> 00:09:59 Make sense? OK. So let's look at that in detail. 126 00:09:59 --> 00:10:03 And I won't draw these pictures on the board for you because, 127 00:10:03 --> 00:10:08 actually, I want to review it in writing one more time. 128 00:10:08 --> 00:10:12 I'm not going to draw the details of meiosis for you on the board 129 00:10:12 --> 00:10:17 because it just takes too long, and the book does a perfectly good 130 00:10:17 --> 00:10:22 job diagramming it for you. And I'll show you those diagrams in 131 00:10:22 --> 00:10:26 a second. The terms that we use in meiosis are the same terms that we 132 00:10:26 --> 00:10:32 use in mitosis. But there are two rounds, 133 00:10:32 --> 00:10:39 as I mentioned, and they're broken down by meiosis one and meiosis two. 134 00:10:39 --> 00:10:46 In meiosis one you have a prophase, and it's called prophase one. 135 00:10:46 --> 00:10:53 You have a prometaphase, prometaphase one. 136 00:10:53 --> 00:11:00 A metaphase where the chromosomes align on the metaphase plate. 137 00:11:00 --> 00:11:06 And anaphase where the chromosomes get pulled apart by the mitotic 138 00:11:06 --> 00:11:12 spindle, actually, in this case the meiotic spindle. 139 00:11:12 --> 00:11:19 And finally a telophase where they get pulled all the way to the poles. 140 00:11:19 --> 00:11:25 And then there's a second round, meiosis two, where the same terms 141 00:11:25 --> 00:11:32 are applied but they're denoted with twos. 142 00:11:32 --> 00:11:36 So there's a second phase of prophase, of prometaphase, 143 00:11:36 --> 00:11:40 metaphase, anaphase and telophase. And this is where the chromatids 144 00:11:40 --> 00:11:44 align on the chromosome plate and get separated. 145 00:11:44 --> 00:11:49 OK? Now, there's a very key event, and I'm going to draw it for you 146 00:11:49 --> 00:11:53 because it's so important, that takes place during prophase of 147 00:11:53 --> 00:11:57 meiosis one. And this is the distinguishing feature between 148 00:11:57 --> 00:12:02 meiosis and mitosis. As I said in mitosis, 149 00:12:02 --> 00:12:07 the homologs, the two copies of chromosome one, 150 00:12:07 --> 00:12:12 the maternal one and the paternal one for example ignore one another. 151 00:12:12 --> 00:12:16 That's not true in mitosis, in meiosis. In meiosis they bind to 152 00:12:16 --> 00:12:21 one another. So imagine again our, I think I called this the paternal 153 00:12:21 --> 00:12:26 copy of chromosome whatever, one previously. It had four genes 154 00:12:26 --> 00:12:32 that we showed previously. It's represented as two chromatids, 155 00:12:32 --> 00:12:38 which are associated at the centromere. And then you have 156 00:12:38 --> 00:12:44 another homolog, the maternal homolog. 157 00:12:44 --> 00:12:50 It likewise has the same four genes. It's been duplicated so it's 158 00:12:50 --> 00:12:56 represented as two chromatids held together at the centromere. 159 00:12:56 --> 00:13:03 In prophase of meiosis one, these homologs pair. 160 00:13:03 --> 00:13:10 And it's the pairing of the homologs 161 00:13:10 --> 00:13:15 that allows the two to separate faithfully during meiosis one. 162 00:13:15 --> 00:13:19 They also interact in an interesting way that we'll come to 163 00:13:19 --> 00:13:24 in a moment. They don't just pair. They actually undergo interactions 164 00:13:24 --> 00:13:29 between each other which allows them to exchange sequences which is 165 00:13:29 --> 00:13:34 critical for generating diversity amongst our chromosomes. 166 00:13:34 --> 00:13:38 So now I'm going to take you through these steps as shown in your book. 167 00:13:38 --> 00:13:43 This is figure 9.14 in your book. We're going to go through meiosis 168 00:13:43 --> 00:13:47 one first. So in prophase of meiosis one, we've undergone 169 00:13:47 --> 00:13:52 chromosome duplication already into the chromatids. 170 00:13:52 --> 00:13:56 Now the chromosomes are going to condense, and you can see that here. 171 00:13:56 --> 00:14:01 And importantly during prophase the two chromosomes, 172 00:14:01 --> 00:14:06 represented by the four chromatids align. 173 00:14:06 --> 00:14:10 In this picture you're seeing two different chromosomes, 174 00:14:10 --> 00:14:14 a larger one and a smaller one. And you can see that the maternal 175 00:14:14 --> 00:14:18 and paternal copies have paired with one another. OK? 176 00:14:18 --> 00:14:22 So we get pairs of homologs. Still later in prophase they 177 00:14:22 --> 00:14:26 interact in this other fashion that I just alluded to where they 178 00:14:26 --> 00:14:30 actually exchange information. They exchange genetic information. 179 00:14:30 --> 00:14:33 And we'll go through this in a little bit more detail in a bit. 180 00:14:33 --> 00:14:37 At metaphase of meiosis one, metaphase one, 181 00:14:37 --> 00:14:40 the homologs line up on the metaphase plate with one homolog to 182 00:14:40 --> 00:14:44 the left, the other homolog to the right, one homolog to the left, 183 00:14:44 --> 00:14:48 the other homolog to the right. This is one of two possible 184 00:14:48 --> 00:14:51 configurations that could take place here. In fact, 185 00:14:51 --> 00:14:55 in another cell undergoing metaphase one, the red one might be on the 186 00:14:55 --> 00:14:59 left, the blue one on the right, but here the blue one might be one 187 00:14:59 --> 00:15:03 the left, the red one might be on the right. 188 00:15:03 --> 00:15:07 And that's important. You'll see why later. 189 00:15:07 --> 00:15:12 So the homologs line up along the metaphase plate. 190 00:15:12 --> 00:15:16 And now during anaphase one the homologs separate from one another. 191 00:15:16 --> 00:15:21 The two chromatids of each homolog separate from one another, 192 00:15:21 --> 00:15:26 and that's completed in telophase. Now, without an intervening round 193 00:15:26 --> 00:15:30 of DNA duplication, this does not involve another round 194 00:15:30 --> 00:15:35 of S phase, we go straight into meiosis two where again the DNA 195 00:15:35 --> 00:15:40 condenses, a mitotic spindle is built. 196 00:15:40 --> 00:15:44 And now, just like in mitosis, the two chromatids line up along the 197 00:15:44 --> 00:15:48 metaphase plate with one chromatid to the top, the other chromatid to 198 00:15:48 --> 00:15:52 the bottom, one chromatid to the top, the other to the bottom. 199 00:15:52 --> 00:15:56 And then they get separated during anaphase and telophase 200 00:15:56 --> 00:16:02 of meiosis two. The end product of that are germ 201 00:16:02 --> 00:16:09 cells which are now haploid. They have only one copy of each of 202 00:16:09 --> 00:16:15 the chromosomes, one of the big ones and one of the 203 00:16:15 --> 00:16:22 small ones. So that's how you go from a cell that has two copies of 204 00:16:22 --> 00:16:29 each to a cell that has one copy of each. One round of DNA duplication, 205 00:16:29 --> 00:16:36 two rounds of chromosome or chromatid separation. 206 00:16:36 --> 00:16:38 Now, importantly you'll see if you can squint a little bit, 207 00:16:38 --> 00:16:40 that the chromosomes that come out of this process of meiosis don't 208 00:16:40 --> 00:16:42 always look, in fact, never look like the chromosomes that 209 00:16:42 --> 00:16:44 come in. They undergo this process of exchange of genetic information. 210 00:16:44 --> 00:16:54 This process of exchange of genetic 211 00:16:54 --> 00:16:58 information is called meiotic recombination. 212 00:16:58 --> 00:17:08 And I'll show it to you in a figure 213 00:17:08 --> 00:17:14 in a second. But it generates first recombinant chromatids, 214 00:17:14 --> 00:17:20 chromatids that look different from the chromatids that were generated 215 00:17:20 --> 00:17:26 initially. That's why they're called recombinant. 216 00:17:26 --> 00:17:32 And these, when resolved during meiosis two, generate recombinant 217 00:17:32 --> 00:17:40 chromosomes. 218 00:17:40 --> 00:17:48 So, again, if we imagine our two homologs of a given chromosome with 219 00:17:48 --> 00:17:56 the four genes that we talked about previously lined up along the length 220 00:17:56 --> 00:18:04 of those chromosomes, during this process of meiotic 221 00:18:04 --> 00:18:20 recombination -- 222 00:18:20 --> 00:18:29 -- new versions of the chromosomes are produced. We can generate a 223 00:18:29 --> 00:18:39 chromosome which has a little bit of Dad's DNA and a little 224 00:18:39 --> 00:18:46 bit of Mom's DNA. A chromosome that was generated 225 00:18:46 --> 00:18:51 specifically in you. It's your unique contribution to 226 00:18:51 --> 00:18:56 the offspring. It's not solely what you got from 227 00:18:56 --> 00:19:01 Mom or Dad. It's your unique version of that chromosome that's a 228 00:19:01 --> 00:19:07 hybrid between what you got from Mom and what you go from Dad. 229 00:19:07 --> 00:19:11 And this process of meiotic recombination allows for the 230 00:19:11 --> 00:19:15 increased diversity in the population. You don't just pass on 231 00:19:15 --> 00:19:19 what you inherited. You actually mix it up a little bit 232 00:19:19 --> 00:19:23 and pass on new combinations of the alleles that you got from your 233 00:19:23 --> 00:19:27 parents. So this is shown in greater detail here. 234 00:19:27 --> 00:19:32 And, again, gone through in much detail in your book. 235 00:19:32 --> 00:19:36 This is figure 9. 6. Here we are in prophase of 236 00:19:36 --> 00:19:41 meiosis one. The homologs have paired and they've undergone a 237 00:19:41 --> 00:19:45 genetic interaction. The DNA of the paternal and the 238 00:19:45 --> 00:19:50 maternal chromatids have literally exchanged information. 239 00:19:50 --> 00:19:55 That's what this crossover is called. It's referred to as a 240 00:19:55 --> 00:20:00 chiasma. And you can literally see it in the electron microscope. 241 00:20:00 --> 00:20:04 When this gets resolved, like a cut and paste reaction. 242 00:20:04 --> 00:20:08 When this gets resolved, you generate new chromatids. 243 00:20:08 --> 00:20:12 This chromatid has mostly red sequence but a little bit of blue 244 00:20:12 --> 00:20:16 sequence. And this chromatid has mostly blue sequence and a little 245 00:20:16 --> 00:20:20 bit of red sequence. If you think about that with 246 00:20:20 --> 00:20:24 respect to genes in our analogy over here, the red chromosome had alleles 247 00:20:24 --> 00:20:28 that we'll refer to as the white versions of gene one, 248 00:20:28 --> 00:20:32 two, three and four. The blue homolog had the black 249 00:20:32 --> 00:20:36 versions of genes one, two, three and four. The products 250 00:20:36 --> 00:20:41 of this reaction include chromatids that look just like the parental 251 00:20:41 --> 00:20:45 ones, a red chromosome with white one, two, three and four, 252 00:20:45 --> 00:20:49 a black chromosome with, a blue chromosome with black one, 253 00:20:49 --> 00:20:54 two, three and four, but also new chromatids that didn't exist 254 00:20:54 --> 00:20:58 previously, a red one with white one, two, three but a black four, 255 00:20:58 --> 00:21:03 and a blue one with black one two and three and a white four. 256 00:21:03 --> 00:21:13 New versions of the chromosomes. And this is important. It's 257 00:21:13 --> 00:21:23 important for you to understand how genetics works, 258 00:21:23 --> 00:21:34 but it's also important for the species to generate increased 259 00:21:34 --> 00:21:44 diversity which when acted upon by natural selection forces might 260 00:21:44 --> 00:21:54 select out more fit organisms. So that is mitosis, meiosis and 261 00:21:54 --> 00:22:02 meiotic recombination. And we'll be drawing on your 262 00:22:02 --> 00:22:06 knowledge of meiosis and mitotic recombination to understand the 263 00:22:06 --> 00:22:11 principles of genetics. And that will be the next topic 264 00:22:11 --> 00:22:16 that we turn to. Before I do so I want to just 265 00:22:16 --> 00:22:20 mention that this process of meiosis doesn't always work perfectly. 266 00:22:20 --> 00:22:25 No biological system works perfectly. There's always some 267 00:22:25 --> 00:22:29 error rate. And that's true in meiosis in germ cell development, 268 00:22:29 --> 00:22:34 although it's supposed to be the case that during metaphase one the 269 00:22:34 --> 00:22:39 homologs, which are paired together, separate to the two daughters. 270 00:22:39 --> 00:22:44 That doesn't always happen. Occasionally errors take place such 271 00:22:44 --> 00:22:50 that one daughter gets nothing and the other daughter gets both copies. 272 00:22:50 --> 00:22:55 This is a problem because now when these guys go through meiosis two 273 00:22:55 --> 00:23:01 they have two copies of a given chromosome instead of just one. 274 00:23:01 --> 00:23:05 And if those germ cells, in this case they're eggs, 275 00:23:05 --> 00:23:10 and that's usually the problem in humans where it occurs, 276 00:23:10 --> 00:23:14 if those eggs get fused by a sperm that carries its own copy of that 277 00:23:14 --> 00:23:19 chromosome the zygote, instead of having just two copies, 278 00:23:19 --> 00:23:24 has three. And this is a situation called trisomy, 279 00:23:24 --> 00:23:29 an extra copy of a given chromosome. The opposite can happen as well. 280 00:23:29 --> 00:23:32 This guy, this egg, if it were to be fertilized would 281 00:23:32 --> 00:23:36 have only a single copy of that given chromosome. 282 00:23:36 --> 00:23:40 That would be monosomy, single instead of two. This does 283 00:23:40 --> 00:23:44 happen during human development. In the vast majority of cases when 284 00:23:44 --> 00:23:48 it happens it's incompatible with early development and the fetus 285 00:23:48 --> 00:23:52 aborts. There are a few examples where the fetus can actually make it 286 00:23:52 --> 00:23:56 quite late in gestation and even be born but then doesn't 287 00:23:56 --> 00:24:00 thrive thereafter. But there's one example where the 288 00:24:00 --> 00:24:04 fetus comes to term, is born and the individual can 289 00:24:04 --> 00:24:08 survive, and that's chromosome 21 trisomy or Down syndrome. 290 00:24:08 --> 00:24:12 This happens when during meiosis one nondisjunction takes place such 291 00:24:12 --> 00:24:17 that two copies of chromosome 21 wind up in an egg. 292 00:24:17 --> 00:24:21 Sperm comes along and delivers another copy of chromosome 21. 293 00:24:21 --> 00:24:25 Now that zygote is trisomic for chromosome 21. 294 00:24:25 --> 00:24:30 And you can see the karyotype here. 295 00:24:30 --> 00:24:34 Everything else is diploid but this has three copies of chromosome 21. 296 00:24:34 --> 00:24:38 And this leads to a characteristic defect in development which results 297 00:24:38 --> 00:24:42 in an individual with very characteristic features. 298 00:24:42 --> 00:24:46 And this extra copy of 21 is responsible for this too much gene 299 00:24:46 --> 00:24:50 product from the genes on chromosome 21. And I don't remember how many 300 00:24:50 --> 00:24:54 there are. There are 600 or so genes on chromosome 21. 301 00:24:54 --> 00:24:58 Having too much of some or some of them, some combination of them, 302 00:24:58 --> 00:25:02 too much product from those leads to defects in development, 303 00:25:02 --> 00:25:06 which results in this very clear phenotype. 304 00:25:06 --> 00:25:10 So meiosis usually insures that you get just one copy of each 305 00:25:10 --> 00:25:15 chromosomes, but it doesn't always work. And this can be one 306 00:25:15 --> 00:25:19 consequence. OK. Let's take a breath and change 307 00:25:19 --> 00:25:24 gears. So we're going to move now from mitosis and meiosis to genetics 308 00:25:24 --> 00:25:29 and genetic principles, and specifically Mendelian genetics. 309 00:25:29 --> 00:25:32 So what we want to now begin to understand is besides the mechanics, 310 00:25:32 --> 00:25:36 what are the consequences? What happens when you inherit alleles of 311 00:25:36 --> 00:25:40 given genes? What is the effect of the inheritance of those alleles and 312 00:25:40 --> 00:25:44 what are the principles that guide that? Why is it that when a child 313 00:25:44 --> 00:25:47 is born of two blue-eyed people that child has blue eyes? 314 00:25:47 --> 00:25:51 When a child is born of a brown-eyed person and blue-eyes 315 00:25:51 --> 00:25:55 person that child is likely to have brown eyes, but not always. 316 00:25:55 --> 00:25:59 Maybe they'd have blue eyes. What governs the presentation of a 317 00:25:59 --> 00:26:03 given trait based on the genes that that individual inherits? 318 00:26:03 --> 00:26:06 Or more precisely the alleles of the genes that individual inherits. 319 00:26:06 --> 00:26:10 You might actually be able to see that the murderer can be seen in the 320 00:26:10 --> 00:26:13 reflection of this person's eye right here. You've got to look 321 00:26:13 --> 00:26:17 carefully. We can learn a lot about this by looking at inheritance 322 00:26:17 --> 00:26:20 patterns in humans. And that's increasingly powerful 323 00:26:20 --> 00:26:24 given our knowledge of the human genome today. There's a lot more we 324 00:26:24 --> 00:26:28 can do in human genetics today than we could have done ten years ago. 325 00:26:28 --> 00:26:32 But the field has actually been brought along to this point using 326 00:26:32 --> 00:26:36 genetics in model organisms. And this is a fly, a fruit fly, 327 00:26:36 --> 00:26:40 drosophila melanogaster, a major genetic organism in biology. 328 00:26:40 --> 00:26:44 And you can see again that you can isolate flies with different colored 329 00:26:44 --> 00:26:48 eyes, red eyes, white eyes, dark eyes. 330 00:26:48 --> 00:26:52 And you can understand the principles of genetics by crossing, 331 00:26:52 --> 00:26:56 mating flies together and looking at what happens in the eye color of the 332 00:26:56 --> 00:27:00 offspring of flies that start off with a given eye color. 333 00:27:00 --> 00:27:05 Now, the principles that guide us in our thinking about genetics derive 334 00:27:05 --> 00:27:10 from this individual here whose name is Gregor Mendel. 335 00:27:10 --> 00:27:15 And the principles that he laid down are referred to as Mendelian 336 00:27:15 --> 00:27:21 inheritance. And he, through work that I'll briefly 337 00:27:21 --> 00:27:26 summarize, developed certain laws of inheritance which turned 338 00:27:26 --> 00:27:31 out to be true. And we use them even now as we think 339 00:27:31 --> 00:27:35 about how genes and alleles get passed on through the generations. 340 00:27:35 --> 00:27:40 Mendel lived in the 1800s. He did his work around 1850s, 341 00:27:40 --> 00:27:44 1860s. His organism was the pea plant and the peas that give rise to 342 00:27:44 --> 00:27:48 the pea plant. And he spent a lot of time 343 00:27:48 --> 00:27:53 observing peas and pea plants, breading or crossing pea plants 344 00:27:53 --> 00:27:57 together, looking at the products of those crosses and coming 345 00:27:57 --> 00:28:01 up with these theories. He published a paper on that work in, 346 00:28:01 --> 00:28:04 I think, 1865, and it was roundly ignored. 347 00:28:04 --> 00:28:07 Nobody paid any attention. I should have mentioned that he was an 348 00:28:07 --> 00:28:10 Austrian monk. He lived up in the hills in Austria 349 00:28:10 --> 00:28:13 and did his work largely in seclusion. But he did, 350 00:28:13 --> 00:28:16 in fact, publish a paper in 1865 reporting his principles of 351 00:28:16 --> 00:28:19 inheritance. And he was largely ignored until about 50 years later 352 00:28:19 --> 00:28:22 when other workers started to do similar things and basically 353 00:28:22 --> 00:28:25 rediscovered these principles that he had laid down so many years 354 00:28:25 --> 00:28:28 before. And we now give him credit for coming up with these principles 355 00:28:28 --> 00:28:32 in the first place. So Mendel focused on traits, 356 00:28:32 --> 00:28:37 traits that he could observe in the pea plant or in the peas themselves. 357 00:28:37 --> 00:28:42 And this is an example of the traits that he might look at. 358 00:28:42 --> 00:28:47 You may know that peas can come in different shapes and textures. 359 00:28:47 --> 00:28:52 There are peas that are smooth. There are peas that are wrinkled. 360 00:28:52 --> 00:28:57 And Mendel wondered what controlled whether a pea was smooth 361 00:28:57 --> 00:29:01 or wrinkled. If you crossed a pea plant that 362 00:29:01 --> 00:29:04 would have produced smooth peas with a pea plant that would have produced 363 00:29:04 --> 00:29:08 wrinkled peas, do you get smooth or wrinkled peas? 364 00:29:08 --> 00:29:11 The principles that guided the thinking previously were that this 365 00:29:11 --> 00:29:14 was some sort of a mixture. If you had one type and another 366 00:29:14 --> 00:29:18 type, the offspring would have some intermediate type. 367 00:29:18 --> 00:29:21 There was sort of a mixing of genetic information, 368 00:29:21 --> 00:29:24 not really referred to as genetic information at the time, 369 00:29:24 --> 00:29:28 but heritable information. And Mendel wondered whether that 370 00:29:28 --> 00:29:32 was true. And then he actually determined that 371 00:29:32 --> 00:29:36 for most things that was not true. One type determined the appearance 372 00:29:36 --> 00:29:41 of the trait in the offspring. In order for you to understand what 373 00:29:41 --> 00:29:46 Mendel did, you have to understand a little bit about pea plants and peas. 374 00:29:46 --> 00:29:50 One thing you need to know is that peas are the embryo. 375 00:29:50 --> 00:29:55 They are the product of fertilization. 376 00:29:55 --> 00:30:00 And when you plant a pea it will develop into a pea plant. 377 00:30:00 --> 00:30:04 And you can score traits either in the pea itself, 378 00:30:04 --> 00:30:09 in the embryo, smooth, wrinkled, dark green, light green, 379 00:30:09 --> 00:30:13 or in the pea plant that results from that pea. 380 00:30:13 --> 00:30:18 Does it have red flowers or white flowers or pink flowers? 381 00:30:18 --> 00:30:23 And importantly you also can fertilize one pea plant from another. 382 00:30:23 --> 00:30:27 You can take the germ cells, the male germ cells or male gametes 383 00:30:27 --> 00:30:32 from one pea plant, and purposely fertilize a female 384 00:30:32 --> 00:30:37 gamete of another pea plant. You can carry out these very precise 385 00:30:37 --> 00:30:41 crosses. Or you can do it within the same pea plant. 386 00:30:41 --> 00:30:45 You can take the male germ cells or gametes and fertilize the female 387 00:30:45 --> 00:30:49 gametes from that same plant, so-called self-pollination. OK? 388 00:30:49 --> 00:30:53 And through this methodology, Mendel was able to very precisely 389 00:30:53 --> 00:30:57 control what the pea plants looked like and how he could 390 00:30:57 --> 00:31:07 manipulate them. 391 00:31:07 --> 00:31:12 Through this process of self-pollination, 392 00:31:12 --> 00:31:18 Mendel was able to generate what he called “pure breading strains”. 393 00:31:18 --> 00:31:23 That is they always produced the same trait. If you cross them 394 00:31:23 --> 00:31:29 together, if you fertilize, self-fertilize them, you always got 395 00:31:29 --> 00:31:34 the same result, always smooth peas or always 396 00:31:34 --> 00:31:40 wrinkled peas or always red flowers or always white flowers. 397 00:31:40 --> 00:31:43 They were pure. There wasn't any heterogeneity. 398 00:31:43 --> 00:31:46 And we're going to refer to these in our discussion as 399 00:31:46 --> 00:31:55 parental strains. 400 00:31:55 --> 00:32:02 And kind of an example of a question that Mendel would want to know is if 401 00:32:02 --> 00:32:09 you took two parental strains and he crossed pollinated from one that 402 00:32:09 --> 00:32:16 always produced smooth peas, and here we're talking about this X 403 00:32:16 --> 00:32:23 represents crossing fertilization, with a plant that always produced 404 00:32:23 --> 00:32:30 wrinkled peas, what did the offspring look like? 405 00:32:30 --> 00:32:36 What did the pea look like in the product of that cross? 406 00:32:36 --> 00:32:43 These parental strains are referred to as P. The product of a cross 407 00:32:43 --> 00:32:49 between two parental strains is called the F1 or first 408 00:32:49 --> 00:33:02 filial generation. 409 00:33:02 --> 00:33:08 And the question Mendel wanted to know was what is the P type in the 410 00:33:08 --> 00:33:14 F1? The answer turns out, for this particular example, 411 00:33:14 --> 00:33:20 to be smooth peas. And the question is why? Based on this kind of 412 00:33:20 --> 00:33:27 observation, Mendel generated a hypothesis. 413 00:33:27 --> 00:33:47 He suggested that traits in the peas, 414 00:33:47 --> 00:34:02 as well as in the subsequent plants, arise from the inheritance of two 415 00:34:02 --> 00:34:12 units. These units we would think of now as 416 00:34:12 --> 00:34:18 two alleles of a given gene. He wasn't thinking of genes or 417 00:34:18 --> 00:34:23 alleles. He was just thinking of what number of things was 418 00:34:23 --> 00:34:29 contributing to this particular trait. And that these two units 419 00:34:29 --> 00:34:35 were delivered to the embryo from each parent. 420 00:34:35 --> 00:34:49 And importantly the parent then has 421 00:34:49 --> 00:35:03 two units so that each parent delivers one of its two alleles to 422 00:35:03 --> 00:35:17 the offspring via the production of germ cells. 423 00:35:17 --> 00:35:20 So everybody has two. They pass on one of those two to 424 00:35:20 --> 00:35:24 their germ cells. And then the embryo is the product 425 00:35:24 --> 00:35:28 of two germ cells coming together generating, once again, 426 00:35:28 --> 00:35:36 something with two units. OK? 427 00:35:36 --> 00:35:41 So let's think about this with respect to pea plants, 428 00:35:41 --> 00:35:46 and specifically the shape of the peas. So the trait that we're 429 00:35:46 --> 00:35:52 interested in is smooth or wrinkled peas. 430 00:35:52 --> 00:36:03 The gene, in our language, 431 00:36:03 --> 00:36:10 is the S gene. It is going to determine whether or not the pea is 432 00:36:10 --> 00:36:18 smooth or wrinkled. And this gene comes in two 433 00:36:18 --> 00:36:25 varieties, two alleles. One is called big S and the other 434 00:36:25 --> 00:36:32 is called little S. In the cross that was done, 435 00:36:32 --> 00:36:39 the plant that always generated smooth peas, which was a pure 436 00:36:39 --> 00:36:46 breeding strain, had the same allele in both copies. 437 00:36:46 --> 00:36:53 It was diploid for the big S allele. Both of its chromosomes that carry 438 00:36:53 --> 00:37:00 the S gene had the big S version of that gene. 439 00:37:00 --> 00:37:07 And the wrinkled plant, the plant that produced wrinkled 440 00:37:07 --> 00:37:15 peas carried two copies of the other allele, little S. 441 00:37:15 --> 00:37:23 These plants produced smooth peas. These plants produced wrinkled peas. 442 00:37:23 --> 00:37:31 When these plants produced germ cells, what allele of this gene gets 443 00:37:31 --> 00:37:38 put into those germ cells? Big S. It's the only one there. 444 00:37:38 --> 00:37:45 So when these plants undergo meiosis they're going to produce 445 00:37:45 --> 00:37:53 germ cells that carry in them the big S gene. When these plants 446 00:37:53 --> 00:38:00 undergo meiosis what allele of the S gene did they put in their 447 00:38:00 --> 00:38:07 germ cells? Little S. These haploid germ cells have the 448 00:38:07 --> 00:38:13 little S gene. Now, when I cross, 449 00:38:13 --> 00:38:19 I take one of these germ cells, mix it with one of those germ cells 450 00:38:19 --> 00:38:25 in the cross, what gene, what genes, what alleles does that 451 00:38:25 --> 00:38:33 offspring inherit? It gets a big S from here and it 452 00:38:33 --> 00:38:41 gets a little S from here. OK? And what do I observe when I 453 00:38:41 --> 00:38:49 make an organism, a pea, that looks like that? 454 00:38:49 --> 00:38:58 What does the trait look like? It's smooth. OK. 455 00:38:58 --> 00:39:04 Now, I've drawn details without given you some of the relevant 456 00:39:04 --> 00:39:11 nomenclature. The parental strain over here had big S, 457 00:39:11 --> 00:39:18 big S. We call that the genotype. A genotype refers to which alleles 458 00:39:18 --> 00:39:25 you have; your genotype. The genotype of the other parental 459 00:39:25 --> 00:39:32 strain is S, S. And the genotype of the offspring is 460 00:39:32 --> 00:39:39 big S, little S. That's the genotype. 461 00:39:39 --> 00:39:46 If you have two of the same alleles it is called being homozygous. 462 00:39:46 --> 00:39:53 This also has two of the same alleles so it is also homozygous for 463 00:39:53 --> 00:40:00 the other allele but still homozygous. 464 00:40:00 --> 00:40:08 If you have one allele of one type and the other allele you are called 465 00:40:08 --> 00:40:16 heterozygous. OK. So that's some relevant terminology. 466 00:40:16 --> 00:40:24 Now, in contrast to the genotype, we also refer to the phenotype. And 467 00:40:24 --> 00:40:33 the phenotype refers to the manifestation of the trait. 468 00:40:33 --> 00:40:40 What you look like. Regardless of what the gene 469 00:40:40 --> 00:40:47 combination or allele combination you have, what do you actually look 470 00:40:47 --> 00:40:54 like? So what is the phenotype of these peas? Smooth. 471 00:40:54 --> 00:41:02 And what is the phenotype of these peas? They're wrinkled. 472 00:41:02 --> 00:41:09 And what is the phenotype of these peas? They're smooth. 473 00:41:09 --> 00:41:17 Based on the patterns that he observed when he crossed two pure 474 00:41:17 --> 00:41:25 breading strains and generated offspring that resembled one of the 475 00:41:25 --> 00:41:33 two pure breading strains, Mendel suggested that in this 476 00:41:33 --> 00:41:41 particular cross the big S unit, we would call it allele, is dominant 477 00:41:41 --> 00:41:48 over little S. If you have a big S allele, 478 00:41:48 --> 00:41:54 regardless of what you have as the other allele, you're going to have 479 00:41:54 --> 00:42:00 the big S trait which is smooth. Big S is dominant over little S. 480 00:42:00 --> 00:42:06 And a related term, little S is recessive to big S. 481 00:42:06 --> 00:42:13 The only way you observe the phenotype associated with the little 482 00:42:13 --> 00:42:20 S allele is if you're homozygous for the little S. If you're 483 00:42:20 --> 00:42:27 heterozygous, as in the case in the middle, you manifest the phenotype 484 00:42:27 --> 00:42:34 associated with the other allele. Dominance and recessive. 485 00:42:34 --> 00:42:41 OK. Now, based on these ideas of inheritance of a single unit or 486 00:42:41 --> 00:42:47 allele from the parents who carry two and the concept of dominance and 487 00:42:47 --> 00:42:54 recessiveness, you can come up with methods for 488 00:42:54 --> 00:43:01 determining the frequency of observing genotypes and phenotypes 489 00:43:01 --> 00:43:08 in crosses such as this. So I want to consider now not a 490 00:43:08 --> 00:43:16 parental cross giving rise to an F1, but rather a cross between F1. We 491 00:43:16 --> 00:43:24 call this a hybrid cross. And because we're focusing on one 492 00:43:24 --> 00:43:32 gene we actually call it a monohybrid cross. 493 00:43:32 --> 00:43:44 The genotypes of the plants that 494 00:43:44 --> 00:43:49 we're going to start with in the F1 generation are as we described 495 00:43:49 --> 00:43:54 previously. They're heterozygous big S, little S. 496 00:43:54 --> 00:44:00 And that's true for one plant and the other. 497 00:44:00 --> 00:44:07 They're both F1s. They're both heterozygous for big S, 498 00:44:07 --> 00:44:14 little S. If we now cross these together, we can think about what 499 00:44:14 --> 00:44:22 germ cells these plants produce. So what are the four products of 500 00:44:22 --> 00:44:29 meiosis look like from this? What do you get in the meiotic 501 00:44:29 --> 00:44:37 products starting with these genotypes? 502 00:44:37 --> 00:44:43 Two of them get big S, two of them get little S. 503 00:44:43 --> 00:44:49 And likewise over here. Two of the germ cells get big S, 504 00:44:49 --> 00:44:55 two of the germ cells get little S. Therefore, half of the germ cells 505 00:44:55 --> 00:45:01 are big S, half are little S. If I think about the frequency of 506 00:45:01 --> 00:45:06 big S germ cells it's one-half. If I think of the frequency of 507 00:45:06 --> 00:45:12 little S germ cells it's one-half. And likewise over here, half of the 508 00:45:12 --> 00:45:17 germ cells are big S, half of the germ cells are little S. 509 00:45:17 --> 00:45:23 Based on this idea I can generate a grid -- 510 00:45:23 --> 00:45:32 -- which will allow me to calculate 511 00:45:32 --> 00:45:37 the frequency of offspring that have four different combinations. 512 00:45:37 --> 00:45:43 If this germ cell combines with this germ cell I'll be big S, 513 00:45:43 --> 00:45:48 big S. If this germ cell combines with this germ cell the genotype 514 00:45:48 --> 00:45:53 will be big S, little S. If this germ cell 515 00:45:53 --> 00:45:59 combines with this germ cell the genotype will be little 516 00:45:59 --> 00:46:04 S, little S. And if this germ cell combines with 517 00:46:04 --> 00:46:08 this germ cell the genotype will be big S, little S. 518 00:46:08 --> 00:46:13 This box, which is a useful device for calculating the frequency of the 519 00:46:13 --> 00:46:17 genotypes that you observe in different crosses, 520 00:46:17 --> 00:46:31 is referred to as a Punnett Square. 521 00:46:31 --> 00:46:36 So let's think about what the numbers would be in such a 522 00:46:36 --> 00:46:42 monohybrid cross. There are three possible genotypes. 523 00:46:42 --> 00:46:48 If you look at the Punnett Square there are three possible genotypes. 524 00:46:48 --> 00:46:54 You can be homozygous big S, big S. You can be homozygous little S, 525 00:46:54 --> 00:47:00 little S. Or you can be heterozygous big S, little S. 526 00:47:00 --> 00:47:07 Those are the three possible genotypes from a cross such as this. 527 00:47:07 --> 00:47:15 The ratio of those genotypes, if you look in the Punnett Square is 528 00:47:15 --> 00:47:23 there is one of these for every one of these and two of these. 529 00:47:23 --> 00:47:31 The ratio of the three genotypes is 1:2:1 as determined by this 530 00:47:31 --> 00:47:37 kind of calculation. The reason that you get that ratio 531 00:47:37 --> 00:47:43 is that a quarter of these, sorry. Half of these germ cells are 532 00:47:43 --> 00:47:48 big S, half of these germ cells are big S, so a quarter plus, 533 00:47:48 --> 00:47:54 times a quarter, sorry, sorry, sorry, I said that wrong. Half of 534 00:47:54 --> 00:48:00 these germ cells are big S. Half of those germ cells are big S. 535 00:48:00 --> 00:48:05 So a half times a half is a quarter. Half of these germ cells are little 536 00:48:05 --> 00:48:10 S. Half of these germ cells are little S. The probability of 537 00:48:10 --> 00:48:15 getting one of each is a half times a half or a quarter. 538 00:48:15 --> 00:48:20 For big S, little S you can do it two different ways, 539 00:48:20 --> 00:48:26 so it's a quarter plus a quarter or a half. 540 00:48:26 --> 00:48:35 The ratio of these fractions is 541 00:48:35 --> 00:48:42 1:2:1 which determines the products that you see. Now, 542 00:48:42 --> 00:48:49 before I let you go, I want you think about the 543 00:48:49 --> 00:48:56 phenotypes. The phenotypes that you observe in these peas is smooth, 544 00:48:56 --> 00:49:03 in these peas is smooth and in these peas wrinkled. 545 00:49:03 --> 00:49:07 So the ratio of phenotypes is 2:1. You'll need to think about why 546 00:49:07 --> 00:49:12 those, sorry, sorry, two plus one is three, 547 00:49:12 --> 00:49:16 3:1. You'll need to think about why those principles give rise to these 548 00:49:16 --> 00:49:19 calculations and these frequencies.