1 00:00:16,673 --> 00:00:18,090 ADAM MARTIN: So today, we're going 2 00:00:18,090 --> 00:00:21,670 to continue with genetics. 3 00:00:21,670 --> 00:00:25,830 And we're going to talk about the rules 4 00:00:25,830 --> 00:00:27,870 or laws of inheritance. 5 00:00:27,870 --> 00:00:30,600 I expect that many, if not all of you 6 00:00:30,600 --> 00:00:33,540 have been exposed to these rules before. 7 00:00:33,540 --> 00:00:35,970 And so what I really want to do today 8 00:00:35,970 --> 00:00:39,210 is make the connection between these laws 9 00:00:39,210 --> 00:00:41,670 and the behavior of chromosomes, such 10 00:00:41,670 --> 00:00:44,400 that when you're thinking about genetics and inheritance 11 00:00:44,400 --> 00:00:50,210 pattern you're thinking about chromosomes undergoing meiosis. 12 00:00:50,210 --> 00:00:54,450 And I wanted to start just to make the point that there 13 00:00:54,450 --> 00:01:01,110 are a number of human traits and human diseases that show 14 00:01:01,110 --> 00:01:04,319 clear inheritance patterns. 15 00:01:04,319 --> 00:01:08,460 And what's shown up here is what's known as a pedigree. 16 00:01:08,460 --> 00:01:10,020 So this is a pedigree. 17 00:01:10,020 --> 00:01:12,000 Let's block this off. 18 00:01:12,000 --> 00:01:17,280 I'm showing you a pedigree, which shows relationships 19 00:01:17,280 --> 00:01:19,380 and a family tree. 20 00:01:19,380 --> 00:01:21,720 And so what you can see-- 21 00:01:21,720 --> 00:01:27,450 what these symbols denote are, you have an open box. 22 00:01:27,450 --> 00:01:30,700 That is an unaffected male. 23 00:01:30,700 --> 00:01:33,050 So open box is an unaffected male. 24 00:01:36,930 --> 00:01:40,440 And what I mean by unaffected is usually 25 00:01:40,440 --> 00:01:42,630 it means they don't have the disease that we're 26 00:01:42,630 --> 00:01:44,850 talking about. 27 00:01:44,850 --> 00:01:47,100 Circles represent females. 28 00:01:47,100 --> 00:01:51,445 And so an open circle would be an unaffected female. 29 00:02:03,340 --> 00:02:06,610 And finally, if you have one of these symbols, 30 00:02:06,610 --> 00:02:11,890 either male or female, and it's shaded in, 31 00:02:11,890 --> 00:02:16,220 that, by convention, represents an affected individual. 32 00:02:16,220 --> 00:02:21,050 So that's an individual that has the disease or trait. 33 00:02:21,050 --> 00:02:26,860 So this is an affected individual. 34 00:02:26,860 --> 00:02:30,820 So this is an example of a disease 35 00:02:30,820 --> 00:02:34,210 that you've already heard about from Professor Imperiali. 36 00:02:34,210 --> 00:02:39,190 This is a family tree that's indicative of a type 37 00:02:39,190 --> 00:02:44,440 of inheritance that's seen in families with a disease called 38 00:02:44,440 --> 00:02:47,200 phenylketonuria. 39 00:02:47,200 --> 00:02:50,200 And you'll remember from Professor Imperiali's lecture, 40 00:02:50,200 --> 00:02:55,570 this is a disease where there's a mutation or allele in which 41 00:02:55,570 --> 00:03:00,150 there is a defective enzyme that can't process the amino acid 42 00:03:00,150 --> 00:03:01,960 phenylalanine. 43 00:03:01,960 --> 00:03:04,960 And so patients with this disorder 44 00:03:04,960 --> 00:03:07,330 have to be very careful about their diet 45 00:03:07,330 --> 00:03:11,330 such that they don't intake too much phenylalanine. 46 00:03:11,330 --> 00:03:15,400 And what you see about this trait or disease 47 00:03:15,400 --> 00:03:18,310 is that it's skipping multiple generations. 48 00:03:18,310 --> 00:03:21,670 And then it manifests itself down here. 49 00:03:21,670 --> 00:03:23,320 I'm not getting any arrow. 50 00:03:23,320 --> 00:03:28,130 So I'm just going to use this pointer here. 51 00:03:28,130 --> 00:03:30,730 So here you see there are several individuals. 52 00:03:30,730 --> 00:03:34,240 There's a male and a female with the disease. 53 00:03:34,240 --> 00:03:38,050 And it results from a relationship 54 00:03:38,050 --> 00:03:40,120 between two first cousins. 55 00:03:40,120 --> 00:03:44,050 So only in this case does the disease sort of appear. 56 00:03:44,050 --> 00:03:49,000 And you can think of this as a recessive trait. 57 00:03:49,000 --> 00:03:52,430 In this case, it's autosomal recessive. 58 00:03:52,430 --> 00:03:58,340 So for PKU, this is exhibiting what's 59 00:03:58,340 --> 00:04:02,350 a type of inheritance known as autosomal recessive. 60 00:04:06,310 --> 00:04:08,050 And the reason that it's recessive 61 00:04:08,050 --> 00:04:10,870 is because if an individual just has 62 00:04:10,870 --> 00:04:13,840 one copy of a functional enzyme, then 63 00:04:13,840 --> 00:04:16,180 they don't have the disease. 64 00:04:16,180 --> 00:04:19,899 So you can see that it's only individuals that 65 00:04:19,899 --> 00:04:22,390 have both defective versions, which 66 00:04:22,390 --> 00:04:26,800 are labeled lowercase a here, that exhibit the disease. 67 00:04:26,800 --> 00:04:32,170 So in the case of PKU, lowercase a represents 68 00:04:32,170 --> 00:04:33,160 the defective enzyme. 69 00:04:38,050 --> 00:04:41,290 And uppercase A denotes a functional enzyme. 70 00:04:48,010 --> 00:04:51,790 Now, it's not shown here, but it's possible 71 00:04:51,790 --> 00:04:58,120 that an ancestor sort of above this parental generation 72 00:04:58,120 --> 00:05:00,760 also exhibited this disease, such that there'd 73 00:05:00,760 --> 00:05:05,930 be a sign that this is being inherited across generations. 74 00:05:05,930 --> 00:05:07,990 So that's not as obvious in this disorder, 75 00:05:07,990 --> 00:05:11,020 because it's a very rare genetic disorder. 76 00:05:11,020 --> 00:05:14,110 But more common disorders, such as color blindness, 77 00:05:14,110 --> 00:05:18,770 show a more clear inheritance from generation to generation. 78 00:05:18,770 --> 00:05:24,320 So is anyone here colorblind? 79 00:05:24,320 --> 00:05:28,100 I ask just to know how to set up my slides as well. 80 00:05:28,100 --> 00:05:29,400 No one's colorblind. 81 00:05:29,400 --> 00:05:32,050 OK, that's good. 82 00:05:32,050 --> 00:05:34,550 Then you'll all see the difference between the image 83 00:05:34,550 --> 00:05:36,680 on the left and the image on the right. 84 00:05:36,680 --> 00:05:38,390 So if you have normal vision, that's 85 00:05:38,390 --> 00:05:41,240 what you see on the left from this fruit stand. 86 00:05:41,240 --> 00:05:46,340 But for those that are missing the red photopigment 87 00:05:46,340 --> 00:05:51,770 in your cone cells, you exhibit color blindness. 88 00:05:51,770 --> 00:05:57,030 And this fruit stand would look like the image on the right. 89 00:05:57,030 --> 00:06:02,530 So this is a clear example of an inherited trait in humans. 90 00:06:02,530 --> 00:06:05,800 And this is an example of an inheritance pattern 91 00:06:05,800 --> 00:06:09,300 that would be similar to human colorblindness. 92 00:06:09,300 --> 00:06:11,700 And here you can see a clear example 93 00:06:11,700 --> 00:06:14,890 where you have an affected individual, an affected 94 00:06:14,890 --> 00:06:16,290 male here. 95 00:06:16,290 --> 00:06:19,350 That male has five daughters, none of which 96 00:06:19,350 --> 00:06:23,430 exhibit the phenotype or disease. 97 00:06:23,430 --> 00:06:28,920 But several of those daughters give rise to progeny, sons, 98 00:06:28,920 --> 00:06:30,390 that have the disease. 99 00:06:30,390 --> 00:06:34,440 So in this case, you see this trait skips a generation. 100 00:06:34,440 --> 00:06:38,460 But essentially, the grandfather here has passed on the trait 101 00:06:38,460 --> 00:06:42,330 to his grandsons. 102 00:06:42,330 --> 00:06:50,160 And so colorblindness is a little bit different from PKU, 103 00:06:50,160 --> 00:06:52,780 not only in the fact that it's more frequent-- 104 00:06:52,780 --> 00:06:55,920 so it's about 10% of males exhibit colorblindness 105 00:06:55,920 --> 00:06:57,640 in the population. 106 00:06:57,640 --> 00:07:01,560 But also you see with PKU you had both a female 107 00:07:01,560 --> 00:07:03,330 and a male affected. 108 00:07:03,330 --> 00:07:06,210 And in this case, you're seeing a preponderance 109 00:07:06,210 --> 00:07:10,030 of affected males, which seems to be not random. 110 00:07:12,810 --> 00:07:16,650 And so this colorblindness exhibits a different type 111 00:07:16,650 --> 00:07:21,280 of inheritance pattern, which is known as sex-linked recessive. 112 00:07:26,760 --> 00:07:30,300 And I'm going to come back to this inheritance pattern 113 00:07:30,300 --> 00:07:32,070 at the end of the lecture. 114 00:07:32,070 --> 00:07:35,460 Because it's actually this type of inheritance pattern 115 00:07:35,460 --> 00:07:38,700 which helped researchers about 100 years ago 116 00:07:38,700 --> 00:07:41,910 make the connection between the unit of heredity 117 00:07:41,910 --> 00:07:45,150 the gene and chromosomes. 118 00:07:45,150 --> 00:07:47,700 So we'll talk about another example 119 00:07:47,700 --> 00:07:52,260 of this type of inheritance pattern at the end. 120 00:07:52,260 --> 00:07:55,050 So for today, what we're going to talk about is 121 00:07:55,050 --> 00:07:58,500 we're going to start with some of the basic laws 122 00:07:58,500 --> 00:08:01,110 of autosomal inheritance. 123 00:08:01,110 --> 00:08:03,420 And so we're going to talk about Gregor 124 00:08:03,420 --> 00:08:07,410 Mendel and his seminal studies in the pea plant. 125 00:08:07,410 --> 00:08:09,390 And then towards the end of the lecture, 126 00:08:09,390 --> 00:08:11,610 we're going to talk about sex linkage. 127 00:08:11,610 --> 00:08:14,790 And I'm going to tell you about work done in fruit flies, 128 00:08:14,790 --> 00:08:18,690 and specifically, their eye color trait, which 129 00:08:18,690 --> 00:08:22,620 led to the linkage between the behavior of genes 130 00:08:22,620 --> 00:08:25,230 and the behavior of chromosomes. 131 00:08:25,230 --> 00:08:27,390 So that's what we have in store for today. 132 00:08:30,280 --> 00:08:34,289 So first, I'm going to tell you a little bit about what 133 00:08:34,289 --> 00:08:36,780 enabled Mendel's theory. 134 00:08:36,780 --> 00:08:40,260 I guess I could start over here. 135 00:08:40,260 --> 00:08:44,159 So what enabled Mendel's theory? 136 00:08:48,190 --> 00:08:51,545 And I presume that most of you have heard about Mendel before. 137 00:08:55,630 --> 00:09:00,150 So there might be a little bit of a reminder for you, 138 00:09:00,150 --> 00:09:02,580 but I also hope that we kind of make 139 00:09:02,580 --> 00:09:06,870 a very clear connection between Mendel's theory 140 00:09:06,870 --> 00:09:09,330 and the behavior of chromosomes. 141 00:09:09,330 --> 00:09:15,090 So Mendel did his seminal studies using the pea plant. 142 00:09:15,090 --> 00:09:18,870 And one aspect of pea plant biology 143 00:09:18,870 --> 00:09:21,900 that was really essential for Mendel's theory 144 00:09:21,900 --> 00:09:31,080 is that you can both self-pollinate pea plants, 145 00:09:31,080 --> 00:09:35,400 meaning you can take the male gametes from a pea plant 146 00:09:35,400 --> 00:09:38,150 and mate it to the female gametes from the same pea 147 00:09:38,150 --> 00:09:38,670 plant. 148 00:09:38,670 --> 00:09:42,450 So it's entirely within the same plant. 149 00:09:42,450 --> 00:09:47,250 So you can self-pollinate, meaning you do a cross-- 150 00:09:47,250 --> 00:09:51,150 you basically cross a plant to itself, which, obviously, 151 00:09:51,150 --> 00:09:52,710 we can't do with humans. 152 00:09:52,710 --> 00:09:55,050 You can't do with many organisms. 153 00:09:55,050 --> 00:09:59,250 Or you can cross-pollinate, meaning 154 00:09:59,250 --> 00:10:03,150 you take the male gamete from one plant, 155 00:10:03,150 --> 00:10:05,520 and you combine it with the female gamete 156 00:10:05,520 --> 00:10:06,525 from a different plant. 157 00:10:13,740 --> 00:10:15,810 And as we go through Mendel's experiments, 158 00:10:15,810 --> 00:10:18,690 you'll see how this was used to define 159 00:10:18,690 --> 00:10:20,220 the rules of inheritance. 160 00:10:24,240 --> 00:10:29,610 Another property of the pea plants and something 161 00:10:29,610 --> 00:10:31,800 that Mendel took advantage of was he 162 00:10:31,800 --> 00:10:39,420 chose traits of pea plants that exhibited a very clear dominant 163 00:10:39,420 --> 00:10:40,770 or recessive phenotype. 164 00:10:45,840 --> 00:10:54,180 So he used visible traits, visible traits 165 00:10:54,180 --> 00:10:57,430 with a very clear dominance or recessiveness. 166 00:11:10,240 --> 00:11:14,540 And if we go back to our example of PKU, 167 00:11:14,540 --> 00:11:19,330 you can see how this human disorder, the genes that 168 00:11:19,330 --> 00:11:21,160 determine this disorder-- 169 00:11:21,160 --> 00:11:25,420 the alleles have a very clear dominance or recessiveness. 170 00:11:25,420 --> 00:11:30,940 The dominant allele is often denoted with a capital letter. 171 00:11:30,940 --> 00:11:35,200 In this case for PKU, you we used capital letter A. 172 00:11:35,200 --> 00:11:39,750 Or in this case, the disease allele was lower case a. 173 00:11:39,750 --> 00:11:41,980 And that's recessive. 174 00:11:41,980 --> 00:11:47,530 And if an allele has dominance, what that essentially means 175 00:11:47,530 --> 00:11:51,220 is that being homozygous for the dominant allele 176 00:11:51,220 --> 00:11:56,980 is equivalent to having just one copy of that allele. 177 00:11:56,980 --> 00:12:00,190 And so I think if you think of the PKU example, 178 00:12:00,190 --> 00:12:01,810 this is very clear. 179 00:12:01,810 --> 00:12:05,050 Because the disease phenotype results 180 00:12:05,050 --> 00:12:07,420 from a defective enzyme. 181 00:12:07,420 --> 00:12:11,680 So if you just have one copy of the enzyme that's functional, 182 00:12:11,680 --> 00:12:17,230 then the human can have wild type or normal function. 183 00:12:17,230 --> 00:12:20,680 So in order to really lack function of this enzyme, 184 00:12:20,680 --> 00:12:23,790 you need to be homozygous for the non-functional allele. 185 00:12:26,320 --> 00:12:29,980 So you need to not have any normal copy of that enzyme. 186 00:12:29,980 --> 00:12:32,920 Because if you just have one copy of that enzyme, you're OK. 187 00:12:32,920 --> 00:12:34,690 Because you have an enzyme that's 188 00:12:34,690 --> 00:12:37,390 functional and will carry out that function 189 00:12:37,390 --> 00:12:38,620 in the cells of your body. 190 00:12:42,180 --> 00:12:49,500 The last point I want to make is that Mendel did his experiments 191 00:12:49,500 --> 00:12:53,580 starting with what are known as pure breeding lines. 192 00:12:53,580 --> 00:12:55,605 So he started with pure breeding lines. 193 00:13:00,780 --> 00:13:03,030 And what I mean by pure breeding are 194 00:13:03,030 --> 00:13:05,640 these are lines that if you take these plants 195 00:13:05,640 --> 00:13:08,760 and just self-cross them over and over again, generation 196 00:13:08,760 --> 00:13:11,490 to generation, they will only give rise 197 00:13:11,490 --> 00:13:16,230 to plants with traits that reflect 198 00:13:16,230 --> 00:13:18,390 the parental generation. 199 00:13:18,390 --> 00:13:20,220 So there's basically no variation. 200 00:13:25,560 --> 00:13:29,370 And you'll see in just a moment that another way 201 00:13:29,370 --> 00:13:33,270 to denote pure breeding means that for a certain trait 202 00:13:33,270 --> 00:13:37,710 you have an allele combination which is homozygous. 203 00:13:37,710 --> 00:13:41,400 So another way to think of pure breeding lines 204 00:13:41,400 --> 00:13:47,690 are these are plants that have a homozygous allele composition. 205 00:13:47,690 --> 00:13:50,610 Homozygous meaning that either they 206 00:13:50,610 --> 00:13:54,490 have two copies of one allele or two copies of the other allele. 207 00:14:04,710 --> 00:14:07,710 I just want to make the point that Mendel 208 00:14:07,710 --> 00:14:11,400 had to overcome a number of hurdles 209 00:14:11,400 --> 00:14:13,090 in order to get these results. 210 00:14:13,090 --> 00:14:16,020 And Mendel is not exactly your sort 211 00:14:16,020 --> 00:14:21,810 of clear example of a success story. 212 00:14:21,810 --> 00:14:25,380 So Mendel applied to get a teaching certificate 213 00:14:25,380 --> 00:14:27,000 in university. 214 00:14:27,000 --> 00:14:29,370 And he failed out. 215 00:14:29,370 --> 00:14:34,350 And I'll quote one of his instructors who said, I quote, 216 00:14:34,350 --> 00:14:36,930 "He lacks insight and the requisite clarity 217 00:14:36,930 --> 00:14:39,600 of knowledge." 218 00:14:39,600 --> 00:14:42,570 So that guy feels stupid. 219 00:14:42,570 --> 00:14:46,980 So next-- so Mendel did his experiments. 220 00:14:46,980 --> 00:14:53,190 And the significance of his work was never 221 00:14:53,190 --> 00:14:55,080 recognized throughout his lifetime. 222 00:14:55,080 --> 00:14:58,950 He did his experiments in the 1850s and '60s. 223 00:14:58,950 --> 00:15:00,960 He died in 1884. 224 00:15:00,960 --> 00:15:04,200 He died not knowing at all what the significance of his work 225 00:15:04,200 --> 00:15:05,130 was. 226 00:15:05,130 --> 00:15:09,420 Because his work was then found again in the early 1900s 227 00:15:09,420 --> 00:15:12,840 by the likes of Thomas Hunt Morgan and others. 228 00:15:12,840 --> 00:15:15,600 And they made the connection between Mendel's laws 229 00:15:15,600 --> 00:15:18,180 of inheritance and chromosomes. 230 00:15:18,180 --> 00:15:19,830 And it was really then that Mendel 231 00:15:19,830 --> 00:15:22,230 became the father of genetics. 232 00:15:22,230 --> 00:15:25,200 Because then there was a physical model 233 00:15:25,200 --> 00:15:27,180 for how inheritance was working. 234 00:15:29,790 --> 00:15:32,160 But he died before that happened. 235 00:15:32,160 --> 00:15:36,300 So he didn't realize that he was the success that we now 236 00:15:36,300 --> 00:15:37,920 know him to be. 237 00:15:37,920 --> 00:15:39,730 Another interesting story. 238 00:15:39,730 --> 00:15:42,390 He started his work with mice. 239 00:15:42,390 --> 00:15:46,140 He wanted to breed mice with different coat colors. 240 00:15:46,140 --> 00:15:48,570 But he got in trouble with his bishop, 241 00:15:48,570 --> 00:15:52,320 because his bishop didn't approve of him promoting sex 242 00:15:52,320 --> 00:15:54,960 among these mice. 243 00:15:54,960 --> 00:16:00,960 Luckily, his bishop didn't take a plant biology course. 244 00:16:00,960 --> 00:16:02,925 Because of course, plants also have sex. 245 00:16:05,970 --> 00:16:08,490 But he had to under come a number of hurdles. 246 00:16:08,490 --> 00:16:11,160 But he took advantage of his garden. 247 00:16:11,160 --> 00:16:14,550 And I was talking to someone in my lab the other day. 248 00:16:14,550 --> 00:16:17,400 And she said, you know what's great about Mendel? 249 00:16:17,400 --> 00:16:18,780 He had a garden. 250 00:16:18,780 --> 00:16:21,630 And he just didn't put it on Instagram. 251 00:16:21,630 --> 00:16:25,660 So he used his garden to his advantage. 252 00:16:25,660 --> 00:16:29,820 And so with his modest garden, he 253 00:16:29,820 --> 00:16:35,430 came up with what are now known as the rules of inheritance. 254 00:16:35,430 --> 00:16:37,500 And I'll start with Mendel's first law. 255 00:16:44,440 --> 00:16:47,580 So Mendel's first law is that every adult 256 00:16:47,580 --> 00:16:51,840 has a pair of genes for a given trait. 257 00:16:51,840 --> 00:16:55,590 And these are now what we refer to as alleles. 258 00:16:55,590 --> 00:16:58,110 And we now refer to them as genes as well. 259 00:16:58,110 --> 00:17:00,150 Mendel did not use the term gene. 260 00:17:00,150 --> 00:17:05,400 He just had these abstract sort of units of heredity. 261 00:17:05,400 --> 00:17:07,980 So his first law states that, every adult 262 00:17:07,980 --> 00:17:12,690 has two sort of units of heredity that can be different. 263 00:17:12,690 --> 00:17:16,770 And that they split during the formation of the gametes. 264 00:17:16,770 --> 00:17:20,160 And the probability that a gamete 265 00:17:20,160 --> 00:17:23,520 will have a given allele or a given unit 266 00:17:23,520 --> 00:17:26,819 is equal probability. 267 00:17:26,819 --> 00:17:30,870 So what I hope you can see is that this law, which 268 00:17:30,870 --> 00:17:34,200 is stated up there, is a direct result 269 00:17:34,200 --> 00:17:38,530 of the segregation of homologous chromosomes during meiosis 1. 270 00:17:53,940 --> 00:17:55,720 Mendel did not know that. 271 00:17:55,720 --> 00:17:59,850 But now looking back, we can see how this manifests itself. 272 00:18:03,660 --> 00:18:08,130 And so during meiosis 1, you recall 273 00:18:08,130 --> 00:18:10,770 that the homologous chromosomes here 274 00:18:10,770 --> 00:18:13,020 line up at the metaphase plate. 275 00:18:13,020 --> 00:18:16,080 And they line up opposite each other, 276 00:18:16,080 --> 00:18:20,970 such that some of the gametes will get the capital Y 277 00:18:20,970 --> 00:18:22,620 allele shown here. 278 00:18:22,620 --> 00:18:24,450 And the other half of the gametes 279 00:18:24,450 --> 00:18:27,000 will get this lower case y allele. 280 00:18:27,000 --> 00:18:30,630 So there's a 50% probability of a gamete 281 00:18:30,630 --> 00:18:34,110 either having one or the other. 282 00:18:34,110 --> 00:18:35,610 And of course, in meiosis 1, this 283 00:18:35,610 --> 00:18:39,690 is referred to as a reduction or division. 284 00:18:39,690 --> 00:18:42,060 Because the homologues are split. 285 00:18:42,060 --> 00:18:45,180 And so the genetic content of the gametes 286 00:18:45,180 --> 00:18:47,310 are divided in half. 287 00:18:51,630 --> 00:18:57,250 So Mendel's first law, the evidence for it 288 00:18:57,250 --> 00:19:03,240 were the results of what is known as a monohybrid cross. 289 00:19:03,240 --> 00:19:08,580 So Mendel did what is known as a monohybrid cross where 290 00:19:08,580 --> 00:19:16,170 he took pea plants that were pure breeding for two 291 00:19:16,170 --> 00:19:17,640 different traits. 292 00:19:17,640 --> 00:19:19,950 One was their pea color. 293 00:19:19,950 --> 00:19:22,590 So it's yellow peas versus green peas. 294 00:19:22,590 --> 00:19:28,740 And he made a hybrid where he takes a yellow plant that 295 00:19:28,740 --> 00:19:31,590 arises from yellow peas and crosses it 296 00:19:31,590 --> 00:19:36,480 to a plant from a green pea. 297 00:19:39,030 --> 00:19:41,310 And this is known as the parental generation. 298 00:19:49,710 --> 00:19:54,990 And so the result of this cross is that all of the peas 299 00:19:54,990 --> 00:19:57,090 were yellow. 300 00:19:57,090 --> 00:19:57,975 So 100%. 301 00:20:00,740 --> 00:20:05,100 This cross results in 100% yellow peas. 302 00:20:05,100 --> 00:20:09,300 This is known as the first filial generation, or the F1. 303 00:20:12,750 --> 00:20:15,630 And that should indicate to you which of these traits 304 00:20:15,630 --> 00:20:17,040 is dominant. 305 00:20:17,040 --> 00:20:20,760 Because if you take yellow peas and you cross it to green peas, 306 00:20:20,760 --> 00:20:23,070 and you get yellow peas, that means 307 00:20:23,070 --> 00:20:28,410 that the trait for yellow peas is dominant. 308 00:20:28,410 --> 00:20:33,540 So for the rest of this, I will denote the gene allele 309 00:20:33,540 --> 00:20:37,590 that confers yellow peas as capital Y and the gene 310 00:20:37,590 --> 00:20:42,270 allele that encodes for green peas as lower case y. 311 00:20:42,270 --> 00:20:46,570 And you see what I'm doing here is I'm putting the phenotype-- 312 00:20:46,570 --> 00:20:50,160 I'm describing the phenotype there, 313 00:20:50,160 --> 00:20:54,450 which is just what the trait is that manifests in the organism. 314 00:20:54,450 --> 00:20:57,150 But the genotype, which is the combination 315 00:20:57,150 --> 00:21:02,250 of alleles in the organism, I'm showing beneath the phenotype. 316 00:21:05,790 --> 00:21:09,030 And if these gene alleles are splitting 317 00:21:09,030 --> 00:21:12,750 during gamete formation and then recombining 318 00:21:12,750 --> 00:21:18,390 during the formation of a new plant, then, in this case, 319 00:21:18,390 --> 00:21:24,280 this hybrid plant is going to have 320 00:21:24,280 --> 00:21:29,500 one allele that's capital Y and one allele that's lowercase y. 321 00:21:29,500 --> 00:21:31,840 And because these two alleles are different, 322 00:21:31,840 --> 00:21:34,960 this situation is known as heterozygous. 323 00:21:34,960 --> 00:21:38,860 So this is a heterozygous plant. 324 00:21:38,860 --> 00:21:44,500 You can think of pure breeding being analogous to homozygous. 325 00:21:44,500 --> 00:21:47,810 Because if you cross yellow pea plant to itself, 326 00:21:47,810 --> 00:21:49,780 you will only get back yellow peas. 327 00:21:49,780 --> 00:21:51,460 So it breeds true. 328 00:21:51,460 --> 00:21:53,770 You can think of a hybrid as being 329 00:21:53,770 --> 00:21:56,970 equivalent to heterozygous, because there are two gene 330 00:21:56,970 --> 00:21:59,620 alleles. 331 00:21:59,620 --> 00:22:02,590 So then what Mendel did is he didn't stop there. 332 00:22:02,590 --> 00:22:07,820 He's self-crossed or self-pollinated 333 00:22:07,820 --> 00:22:11,575 these F1 plants and looked at the resulting seeds. 334 00:22:14,590 --> 00:22:18,550 And so in the F2 generation, what he found 335 00:22:18,550 --> 00:22:23,920 is that he got back both the parental phenotypes-- 336 00:22:23,920 --> 00:22:31,720 so 75% of the progeny were yellow, had yellow peas. 337 00:22:34,390 --> 00:22:37,900 And 25% had green peas. 338 00:22:41,860 --> 00:22:43,990 So there is this 3-to-1 ratio here. 339 00:22:46,760 --> 00:22:53,120 Now, if we think about this in terms of Mendel's first law, 340 00:22:53,120 --> 00:22:55,010 where there's a segregation of these 341 00:22:55,010 --> 00:22:58,580 alleles during the formation of gametes, 342 00:22:58,580 --> 00:23:01,250 and there's an equal probability of having 343 00:23:01,250 --> 00:23:03,440 either one of these alleles-- 344 00:23:03,440 --> 00:23:07,910 if we think about this cross here, 345 00:23:07,910 --> 00:23:11,330 these plants, both the male and female side, 346 00:23:11,330 --> 00:23:15,590 are producing gametes that are either big Y or little y. 347 00:23:22,640 --> 00:23:26,510 So this would be the female here. 348 00:23:26,510 --> 00:23:30,890 And so because they're separating, 349 00:23:30,890 --> 00:23:34,970 and there's a 1/2 probability of having 350 00:23:34,970 --> 00:23:39,330 either the capital Y or little y allele for the male-- 351 00:23:39,330 --> 00:23:41,300 and there's also a 1/2 probability 352 00:23:41,300 --> 00:23:47,660 of having either of these alleles for the female. 353 00:23:47,660 --> 00:23:50,930 So if you look at the possible combination of gametes 354 00:23:50,930 --> 00:23:54,380 that could give rise to the F2 generation, 355 00:23:54,380 --> 00:24:00,590 you have some that will be pure breeding yellow. 356 00:24:00,590 --> 00:24:02,600 And the probability here would be 357 00:24:02,600 --> 00:24:04,880 the joint probability of having this gamete 358 00:24:04,880 --> 00:24:09,080 and this gamete, which is one quarter. 359 00:24:09,080 --> 00:24:11,430 You then have two classes here that 360 00:24:11,430 --> 00:24:16,910 have one copy of the dominant allele 361 00:24:16,910 --> 00:24:18,860 and one copy of the recessive allele. 362 00:24:24,190 --> 00:24:26,560 So these will have the same genotype. 363 00:24:26,560 --> 00:24:29,140 And these three will have the same phenotype. 364 00:24:29,140 --> 00:24:31,510 They'll all be yellow peas. 365 00:24:31,510 --> 00:24:34,600 And so if you add up the probabilities of all three 366 00:24:34,600 --> 00:24:40,150 of these, you can see that 3/4 will be yellow. 367 00:24:40,150 --> 00:24:46,360 So 3/4 of the progeny will have the yellow phenotype. 368 00:24:46,360 --> 00:24:50,050 And you can see that another quarter of the progeny 369 00:24:50,050 --> 00:24:55,090 have the chance of getting two copies of the recessive allele, 370 00:24:55,090 --> 00:24:56,290 and therefore will be green. 371 00:24:59,050 --> 00:25:03,280 So just by considering this as a probability problem, which 372 00:25:03,280 --> 00:25:05,650 is what Mendel did, you can explain 373 00:25:05,650 --> 00:25:11,560 the ratios of the progeny that Mendel observed in his crosses. 374 00:25:16,030 --> 00:25:18,280 And I want to point out the parallels 375 00:25:18,280 --> 00:25:22,900 between this simple cross with peas 376 00:25:22,900 --> 00:25:26,860 and the inheritance pattern shown by PKU, 377 00:25:26,860 --> 00:25:29,650 or phenylketonuria. 378 00:25:29,650 --> 00:25:33,460 So notice here you have green peas 379 00:25:33,460 --> 00:25:35,320 in the parental generation. 380 00:25:35,320 --> 00:25:39,610 But green pea skips a generation and only appears again 381 00:25:39,610 --> 00:25:41,890 in a subsequent generation. 382 00:25:41,890 --> 00:25:44,140 So that's a lot like PKU, where you 383 00:25:44,140 --> 00:25:46,000 can see there's multiple generations that 384 00:25:46,000 --> 00:25:49,660 go by where the trait doesn't manifest itself. 385 00:25:49,660 --> 00:25:53,890 But then it pops up again in that later generation where you 386 00:25:53,890 --> 00:25:58,300 have inbreeding in this family. 387 00:25:58,300 --> 00:26:03,910 So there's a clear connection between the results that Mendel 388 00:26:03,910 --> 00:26:06,340 got and cases of human disease. 389 00:26:08,890 --> 00:26:12,130 Now we're going to go on and talk about Mendel's second law. 390 00:26:24,270 --> 00:26:30,640 So Mendel's second law, which is often 391 00:26:30,640 --> 00:26:33,650 referred to as the law of independent assortment. 392 00:26:41,340 --> 00:26:45,930 And another fortuitous thing in thinking about 393 00:26:45,930 --> 00:26:49,860 Mendel's experimental design and setup which was fortuitous-- 394 00:26:49,860 --> 00:26:51,270 he didn't know it at the time-- 395 00:26:51,270 --> 00:26:53,370 he chose traits that actually were 396 00:26:53,370 --> 00:26:57,000 present on different chromosomes of the pea plant. 397 00:26:57,000 --> 00:26:59,022 So the traits didn't exhibit what 398 00:26:59,022 --> 00:27:01,230 is now known as linkage, where they're are physically 399 00:27:01,230 --> 00:27:04,740 connected on the chromosome. 400 00:27:04,740 --> 00:27:08,790 So this law of independent assortment 401 00:27:08,790 --> 00:27:11,970 can also be explained by thinking about how chromosomes 402 00:27:11,970 --> 00:27:20,760 behave during meiosis, where the alignment of homologous 403 00:27:20,760 --> 00:27:30,450 chromosomes at the metaphase plate of meiosis 1 404 00:27:30,450 --> 00:27:31,620 is essentially random. 405 00:27:36,210 --> 00:27:39,160 So if we take a look at this example here, 406 00:27:39,160 --> 00:27:42,900 you can see I've drawn one particular configuration 407 00:27:42,900 --> 00:27:45,390 for the chromosomes. 408 00:27:45,390 --> 00:27:48,000 And I'm using sort of one gene pair here 409 00:27:48,000 --> 00:27:51,160 and another allele pair here. 410 00:27:51,160 --> 00:27:55,560 And so if the chromosomes were aligned this way, then 411 00:27:55,560 --> 00:27:58,230 when they segregate during meiosis 1 412 00:27:58,230 --> 00:28:01,200 you'd get two classes of gametes. 413 00:28:01,200 --> 00:28:04,020 Some that are capital Y, capital R. 414 00:28:04,020 --> 00:28:08,130 And another class that's lowercase y and r. 415 00:28:08,130 --> 00:28:10,020 So that's one possibility. 416 00:28:10,020 --> 00:28:14,430 But what's equally probable during the alignment 417 00:28:14,430 --> 00:28:18,690 of chromosomes during meiosis 1 is that the chromosomes line up 418 00:28:18,690 --> 00:28:19,680 like this. 419 00:28:19,680 --> 00:28:22,930 So rather than having the dominant alleles 420 00:28:22,930 --> 00:28:25,860 all on one side of the metaphase plate, 421 00:28:25,860 --> 00:28:30,690 you have a dominant allele for one homologous pair on one side 422 00:28:30,690 --> 00:28:34,230 and the other dominant alleles on the other side. 423 00:28:34,230 --> 00:28:38,130 So how they arrange, how these homologous chromosomes arrange 424 00:28:38,130 --> 00:28:41,330 during meiosis is totally random. 425 00:28:41,330 --> 00:28:43,620 And if they arrange like this, you'd 426 00:28:43,620 --> 00:28:46,350 get alternative types of gametes. 427 00:28:46,350 --> 00:28:49,980 You'd get gametes that are uppercase Y, lower case 428 00:28:49,980 --> 00:28:54,960 r, and lower case y, uppercase R. 429 00:28:54,960 --> 00:28:58,050 So this law of independent assortment 430 00:28:58,050 --> 00:29:03,360 can be completely explained by the behavior of the chromosomes 431 00:29:03,360 --> 00:29:06,630 during meiosis 1. 432 00:29:06,630 --> 00:29:09,870 So now I'm going to take you through the experiment that 433 00:29:09,870 --> 00:29:12,140 illustrated this. 434 00:29:12,140 --> 00:29:14,160 And this type of experiment is what 435 00:29:14,160 --> 00:29:15,885 is known as a dihybrid cross. 436 00:29:21,910 --> 00:29:25,620 And so a dihybrid cross is now a cross 437 00:29:25,620 --> 00:29:29,190 where you're taking plants that differ in two traits rather 438 00:29:29,190 --> 00:29:30,480 than just one. 439 00:29:30,480 --> 00:29:32,730 So di stands for two. 440 00:29:32,730 --> 00:29:37,140 And in this case, we're going to consider both pea color. 441 00:29:37,140 --> 00:29:39,680 Again, the pea colors are yellow and green. 442 00:29:42,750 --> 00:29:44,830 But now we're also going to consider p shape. 443 00:29:48,390 --> 00:29:53,203 So you can have peas that are round and peas that 444 00:29:53,203 --> 00:29:53,745 are wrinkled. 445 00:29:58,572 --> 00:30:00,780 All right, I'm going to make use of this board again. 446 00:30:06,240 --> 00:30:11,910 So let's consider the round wrinkled case. 447 00:30:11,910 --> 00:30:16,560 If you set up a cross between a plant that 448 00:30:16,560 --> 00:30:18,960 was from a round seed and a plant that 449 00:30:18,960 --> 00:30:20,460 was from a wrinkled seed-- 450 00:30:23,190 --> 00:30:28,980 and let's say the round allele is dominant, 451 00:30:28,980 --> 00:30:31,050 what would you expect to see in the F1? 452 00:30:36,190 --> 00:30:38,235 So you have-- yes, Carlos. 453 00:30:38,235 --> 00:30:39,110 AUDIENCE: All rounds. 454 00:30:39,110 --> 00:30:42,560 ADAM MARTIN: You'd see all round, exactly right. 455 00:30:42,560 --> 00:30:46,190 So let's go through, now, this cross. 456 00:30:46,190 --> 00:30:50,750 So we're going to have a parental cross where Mendel 457 00:30:50,750 --> 00:30:53,060 took two pure breeding lines. 458 00:30:53,060 --> 00:30:59,270 One of them has yellow round peas. 459 00:30:59,270 --> 00:31:03,650 And he crossed the plant from a yellow round pea 460 00:31:03,650 --> 00:31:06,980 with a plant that was derived from a green wrinkled pea. 461 00:31:16,070 --> 00:31:18,290 And we already know yellow is dominant. 462 00:31:18,290 --> 00:31:22,550 And as Carlos just pointed out, if round is dominant, 463 00:31:22,550 --> 00:31:26,670 then you'd expect all of the peas to be round as well. 464 00:31:26,670 --> 00:31:31,970 So in the F1 generation, what Mendel found is 465 00:31:31,970 --> 00:31:36,485 you have 100% of the progeny that are yellow round peas. 466 00:31:42,470 --> 00:31:44,870 And then similar to the monohybrid cross, 467 00:31:44,870 --> 00:31:50,040 Mendel self-crossed these F1 plants. 468 00:31:50,040 --> 00:31:53,030 And by self-crossing them, he observed 469 00:31:53,030 --> 00:32:05,270 a number of different classes of progeny. 470 00:32:05,270 --> 00:32:09,670 So he got back the parental types, yellow round. 471 00:32:15,640 --> 00:32:19,660 He also got back this other parental type, green wrinkled. 472 00:32:29,020 --> 00:32:33,640 So these, because these were the same combination of traits that 473 00:32:33,640 --> 00:32:37,750 were present in at least one of the original parents, 474 00:32:37,750 --> 00:32:39,952 are known as perennials. 475 00:32:39,952 --> 00:32:40,660 They're parental. 476 00:32:48,350 --> 00:32:50,920 They had the same parental phenotype as one 477 00:32:50,920 --> 00:32:52,690 of the original parents. 478 00:32:52,690 --> 00:32:57,040 But what Mendel observed was two other classes of progeny 479 00:32:57,040 --> 00:32:59,590 which were different combinations 480 00:32:59,590 --> 00:33:02,680 of these traits that weren't present in the original 481 00:33:02,680 --> 00:33:04,420 parental generation. 482 00:33:04,420 --> 00:33:13,840 So those were yellow wrinkled peas and green round peas. 483 00:33:17,990 --> 00:33:20,930 So you'll notice that this combination of traits, 484 00:33:20,930 --> 00:33:25,610 yellow and wrinkled, is not present 485 00:33:25,610 --> 00:33:27,680 in the parental generation. 486 00:33:27,680 --> 00:33:29,720 This is all F2. 487 00:33:29,720 --> 00:33:32,180 This is F2 continued. 488 00:33:32,180 --> 00:33:34,400 You also see green and round were not 489 00:33:34,400 --> 00:33:36,780 present in the parental generation. 490 00:33:36,780 --> 00:33:40,260 So these are referred to as being non-parental. 491 00:33:45,180 --> 00:33:49,670 So this non-parental class is a unique combination 492 00:33:49,670 --> 00:33:53,525 of traits that wasn't present in the original parents. 493 00:33:56,060 --> 00:34:01,220 And what Mendel noted was that in these dihybrid crosses 494 00:34:01,220 --> 00:34:09,530 he always got a stereotypic ratio of 9 to 3 to 3 to 1 495 00:34:09,530 --> 00:34:13,880 for these different classes of combinations of traits. 496 00:34:21,060 --> 00:34:24,810 Now we have to think about the probability. 497 00:34:24,810 --> 00:34:27,670 What leads to this characteristic ratio? 498 00:34:27,670 --> 00:34:29,550 And again, we can think about this just 499 00:34:29,550 --> 00:34:34,530 in terms of probabilities and these different gene 500 00:34:34,530 --> 00:34:38,170 pairs segregating independently of each other. 501 00:34:38,170 --> 00:34:43,440 So we already talked about for a monohybrid cross for pea color, 502 00:34:43,440 --> 00:34:45,690 3/4 of the progeny is yellow. 503 00:34:45,690 --> 00:34:53,400 Because they at least have one dominant allele for color. 504 00:34:53,400 --> 00:34:54,989 And one quarter are green. 505 00:34:58,560 --> 00:35:02,220 So the probability of having this phenotype is 3/4. 506 00:35:02,220 --> 00:35:05,250 The probability of being green is one quarter. 507 00:35:05,250 --> 00:35:11,250 And you can consider pea shape as just a separate monohybrid 508 00:35:11,250 --> 00:35:16,530 cross where the dominant phenotype is also 509 00:35:16,530 --> 00:35:19,500 going to be present at 3/4 probability. 510 00:35:19,500 --> 00:35:21,960 So 3/4 are going to be round. 511 00:35:21,960 --> 00:35:24,315 And one quarter is going to be wrinkled. 512 00:35:28,750 --> 00:35:32,650 So now if we just consider these different classes of progeny 513 00:35:32,650 --> 00:35:36,850 here, we can consider two monohybrid crosses. 514 00:35:36,850 --> 00:35:41,710 And what's the joint probability of being both yellow and round? 515 00:35:41,710 --> 00:35:44,980 So the joint probability of being yellow and round 516 00:35:44,980 --> 00:35:49,220 is 3/4 times 3/4. 517 00:35:49,220 --> 00:35:56,800 So if we have 3/4 times 3/4, that's going to equal 9/16. 518 00:35:56,800 --> 00:35:59,380 Now, if we consider yellow and wrinkled, 519 00:35:59,380 --> 00:36:04,510 that's the joint probability of 3/4 and one quarter. 520 00:36:04,510 --> 00:36:09,310 So this probability is being 3/4 times 521 00:36:09,310 --> 00:36:13,380 one quarter, which is equal to 3/16. 522 00:36:13,380 --> 00:36:16,040 Green and round is similar. 523 00:36:16,040 --> 00:36:18,730 There's a quarter probability of being green 524 00:36:18,730 --> 00:36:21,670 and a 3/4 probability of being round. 525 00:36:21,670 --> 00:36:25,870 So again, you have one quarter times 3/4, 526 00:36:25,870 --> 00:36:28,210 which equals to 3/16. 527 00:36:28,210 --> 00:36:31,570 And the least probable class is being homozygous recessive 528 00:36:31,570 --> 00:36:33,760 for both alleles. 529 00:36:33,760 --> 00:36:36,880 Because there's a one quarter probability of being 530 00:36:36,880 --> 00:36:38,710 recessive for each. 531 00:36:38,710 --> 00:36:42,370 So the joint probability of having all recessive alleles 532 00:36:42,370 --> 00:36:45,540 is one quarter times one quarter, or 1/16. 533 00:36:48,130 --> 00:36:50,260 So you could draw a massive Punnett square 534 00:36:50,260 --> 00:36:51,880 and also derive this. 535 00:36:51,880 --> 00:36:53,740 But really you can just consider it 536 00:36:53,740 --> 00:36:57,310 as two separate monohybrid crosses 537 00:36:57,310 --> 00:36:59,530 and then just calculate joint probabilities. 538 00:37:03,120 --> 00:37:08,700 Any questions on Mendel before I move on? 539 00:37:08,700 --> 00:37:12,510 I'll just point out one thing about Mendel's second law. 540 00:37:12,510 --> 00:37:16,860 This is a rule that I'm going to break, now, in just a minute. 541 00:37:16,860 --> 00:37:20,700 And this law of independent assortment 542 00:37:20,700 --> 00:37:22,695 assumes that there is no linkage. 543 00:37:29,040 --> 00:37:33,780 In other words, seeing this type of inheritance pattern 544 00:37:33,780 --> 00:37:36,330 really depends on the two genes not being 545 00:37:36,330 --> 00:37:39,507 physically connected to each other on the chromosome. 546 00:37:46,670 --> 00:37:51,460 Now we're going to talk about fruit flies. 547 00:37:51,460 --> 00:37:54,040 And specifically, we're going to talk 548 00:37:54,040 --> 00:37:57,430 about a certain trait in fruit flies, which 549 00:37:57,430 --> 00:37:59,680 is their eye color. 550 00:37:59,680 --> 00:38:03,160 I brought some pets to class today. 551 00:38:03,160 --> 00:38:07,420 And so we're going to talk about the white mutant phenotype, 552 00:38:07,420 --> 00:38:10,550 where the fruit flies have a white eye color. 553 00:38:10,550 --> 00:38:13,150 So I have three pairs of vials here. 554 00:38:13,150 --> 00:38:15,370 In one of them, there's the white mutant. 555 00:38:15,370 --> 00:38:17,740 And you're going to see it has white eyes. 556 00:38:17,740 --> 00:38:20,230 And then there's also a corresponding sort 557 00:38:20,230 --> 00:38:23,710 of normal red-eyed flies in the other vial. 558 00:38:23,710 --> 00:38:25,720 So I'll just pass these around. 559 00:38:25,720 --> 00:38:28,330 Hopefully there's enough light that you can see the eye color. 560 00:38:32,410 --> 00:38:35,830 You're able to see the eye color, Jeremy? 561 00:38:35,830 --> 00:38:37,517 Yeah. 562 00:38:37,517 --> 00:38:39,100 You might have to come up to the board 563 00:38:39,100 --> 00:38:41,642 lights at the end of class if you want to see it really well. 564 00:38:47,780 --> 00:38:51,920 So we're going to fast forward from Mendel now and talk 565 00:38:51,920 --> 00:38:55,940 about researchers who picked up on Mendel's work 566 00:38:55,940 --> 00:38:58,305 in the early 1900s. 567 00:38:58,305 --> 00:38:59,930 And specifically, I'm going to tell you 568 00:38:59,930 --> 00:39:04,250 about research done in the lab of Thomas Hunt Morgan, who 569 00:39:04,250 --> 00:39:07,330 had a fly lab at Columbia. 570 00:39:07,330 --> 00:39:10,475 So we're going to talk about Thomas Hunt Morgan. 571 00:39:13,453 --> 00:39:14,870 And actually, we're going to focus 572 00:39:14,870 --> 00:39:18,800 a lot on work done in Morgan's lab 573 00:39:18,800 --> 00:39:20,300 in the next couple of lectures. 574 00:39:20,300 --> 00:39:22,730 Because it turns out his lab also 575 00:39:22,730 --> 00:39:24,650 made the first genetic map. 576 00:39:24,650 --> 00:39:28,700 And we'll talk about that in Friday's lecture. 577 00:39:28,700 --> 00:39:32,030 So the type of inheritance that Morgan defined 578 00:39:32,030 --> 00:39:39,920 is what is now known as sex-linked inheritance, where 579 00:39:39,920 --> 00:39:44,330 a given trait isn't a sorting independently of an organism's 580 00:39:44,330 --> 00:39:50,040 sex, but is somehow connected to it. 581 00:39:50,040 --> 00:39:53,320 And I want to sort of return your attention 582 00:39:53,320 --> 00:39:56,470 to this example of human colorblindness 583 00:39:56,470 --> 00:39:59,290 where there appears to be some sort of connection 584 00:39:59,290 --> 00:40:03,370 between the disease phenotype, in this case, colorblindness, 585 00:40:03,370 --> 00:40:06,400 and the gender of the individuals. 586 00:40:06,400 --> 00:40:10,720 So you see this disease is only affecting males. 587 00:40:10,720 --> 00:40:13,090 And this type of inheritance pattern, 588 00:40:13,090 --> 00:40:15,040 while observed in humans, is really 589 00:40:15,040 --> 00:40:19,060 explained by work done in flies on this white mutant 590 00:40:19,060 --> 00:40:23,020 that you're carrying through the class. 591 00:40:23,020 --> 00:40:27,310 So sex-linked inheritance, the explanation for that is this 592 00:40:27,310 --> 00:40:36,520 is a trait that's carried by a special type of a chromosome 593 00:40:36,520 --> 00:40:38,378 known as a sex chromosome. 594 00:40:42,130 --> 00:40:46,780 So fortunately, for us, flies, like humans, 595 00:40:46,780 --> 00:40:48,280 have a similar set-- 596 00:40:48,280 --> 00:40:59,950 or male flies and humans have an X and a Y chromosome. 597 00:40:59,950 --> 00:41:03,370 So the inheritance kind of is similar between flies 598 00:41:03,370 --> 00:41:06,370 and humans when considering sex linkage. 599 00:41:06,370 --> 00:41:07,945 And females have two X's. 600 00:41:14,440 --> 00:41:16,630 So the presence of these sex chromosomes 601 00:41:16,630 --> 00:41:18,100 was known in the fly. 602 00:41:18,100 --> 00:41:21,610 And it was known that if a fly had an X and a Y chromosome 603 00:41:21,610 --> 00:41:23,200 it would be a male fly. 604 00:41:23,200 --> 00:41:25,420 And if a fly had two X chromosomes 605 00:41:25,420 --> 00:41:28,480 it would be a female fly. 606 00:41:28,480 --> 00:41:36,100 And normally, normal flies have red eyes. 607 00:41:36,100 --> 00:41:41,800 But Morgan's lab was interested in variation in organisms. 608 00:41:41,800 --> 00:41:45,490 And they searched and searched for flies 609 00:41:45,490 --> 00:41:48,970 that had abnormal characteristics or traits. 610 00:41:48,970 --> 00:41:54,120 And what they found in Morgan's lab was a mutant fly. 611 00:41:54,120 --> 00:41:56,170 It was a spontaneous mutant. 612 00:41:56,170 --> 00:41:58,780 But this fly had white eyes. 613 00:41:58,780 --> 00:42:00,050 And it was male. 614 00:42:00,050 --> 00:42:04,870 So they found a single white-eyed male, 615 00:42:04,870 --> 00:42:07,570 which they continued to study for some time. 616 00:42:07,570 --> 00:42:11,140 So they sort of defined some of the rules of its inheritance. 617 00:42:16,650 --> 00:42:19,440 So what Morgan and his lab did was 618 00:42:19,440 --> 00:42:24,270 they set up a set of crosses that look 619 00:42:24,270 --> 00:42:27,210 a lot like Mendel's crosses. 620 00:42:27,210 --> 00:42:29,160 So you have a white-eyed male. 621 00:42:29,160 --> 00:42:30,780 They took a white-eyed male. 622 00:42:36,470 --> 00:42:40,395 And they crossed this white-eyed male to a red-eyed female. 623 00:42:45,750 --> 00:42:49,890 And if you cross a white-eyed male to a red-eyed female, 624 00:42:49,890 --> 00:42:54,000 the result was actually similar to what Mendel had predicted, 625 00:42:54,000 --> 00:42:57,900 which is that 100% of the flies had red eyes. 626 00:43:02,490 --> 00:43:04,020 So that's similar to what you would 627 00:43:04,020 --> 00:43:09,550 expect from a monohybrid cross where red eyes is dominant. 628 00:43:09,550 --> 00:43:12,720 So I'm going to refer to the red eyed allele as an X 629 00:43:12,720 --> 00:43:16,170 with a capital R. And the white-eyed allele is 630 00:43:16,170 --> 00:43:18,720 an X with a lower case r. 631 00:43:18,720 --> 00:43:21,660 Because this gene is present on the X chromosome, 632 00:43:21,660 --> 00:43:25,050 but it's not present on the Y chromosome. 633 00:43:25,050 --> 00:43:27,000 So the Y chromosome is really small. 634 00:43:27,000 --> 00:43:30,390 And so the X chromosome has-- 635 00:43:30,390 --> 00:43:34,380 all of its genes are basically present in one copy 636 00:43:34,380 --> 00:43:35,370 in the male. 637 00:43:35,370 --> 00:43:40,260 And that's going to manifest itself in that sex linkage. 638 00:43:40,260 --> 00:43:43,560 So then they took this F1 generation 639 00:43:43,560 --> 00:43:45,840 where you have red-eyed males. 640 00:43:45,840 --> 00:43:49,040 And they crossed siblings. 641 00:43:49,040 --> 00:43:51,480 So they did a sibling cross. 642 00:43:51,480 --> 00:43:55,770 The one failing of flies as a genetic system is they 643 00:43:55,770 --> 00:43:57,870 can't self-cross. 644 00:43:57,870 --> 00:43:59,880 You have to have a male and a female. 645 00:43:59,880 --> 00:44:06,270 So they crossed two individuals in this F1 generation. 646 00:44:06,270 --> 00:44:07,440 And what they found-- 647 00:44:07,440 --> 00:44:10,080 again, similar to what Mendel would predict-- 648 00:44:10,080 --> 00:44:16,890 is that 75% of the flies had red eyes. 649 00:44:16,890 --> 00:44:20,130 And 25% had white eyes. 650 00:44:20,130 --> 00:44:27,540 So this is behaving a lot like the yellow trait in peas. 651 00:44:27,540 --> 00:44:32,250 Except that all of the white-eyed flies in this F2 652 00:44:32,250 --> 00:44:34,320 generation-- 653 00:44:34,320 --> 00:44:38,340 all of these white-eyed flies were male. 654 00:44:38,340 --> 00:44:44,520 So only the males were getting this trait of white eyes. 655 00:44:44,520 --> 00:44:46,770 And you can see that that's very much reminiscent 656 00:44:46,770 --> 00:44:52,560 of colorblindness, where you have a grandfather that 657 00:44:52,560 --> 00:44:54,690 has white eyes. 658 00:44:54,690 --> 00:44:56,910 And the grandfather is essentially 659 00:44:56,910 --> 00:45:02,070 passing on this trait to his grandsons. 660 00:45:02,070 --> 00:45:05,260 So this pattern of inheritance that happens in the fly 661 00:45:05,260 --> 00:45:09,360 is very similar to that that happens in humans. 662 00:45:09,360 --> 00:45:11,910 So now let's think about how this-- 663 00:45:11,910 --> 00:45:13,830 if we can explain this by thinking 664 00:45:13,830 --> 00:45:16,710 about chromosome segregating. 665 00:45:16,710 --> 00:45:24,330 So if we think about this F1 generation, 666 00:45:24,330 --> 00:45:26,320 we have red-eyed males-- 667 00:45:26,320 --> 00:45:29,010 or actually, let's do the parental cross first, 668 00:45:29,010 --> 00:45:33,180 where we have white-eyed males and we have red-eyed females. 669 00:45:36,520 --> 00:45:41,540 So all of the females are going to get their X from their dad. 670 00:45:41,540 --> 00:45:44,290 And they're going to get a wild type copy of this gene 671 00:45:44,290 --> 00:45:46,510 from their mom. 672 00:45:46,510 --> 00:45:48,940 So all the females are heterozygous 673 00:45:48,940 --> 00:45:51,412 for the white gene. 674 00:45:51,412 --> 00:45:53,620 So I'm going to call it the white gene because that's 675 00:45:53,620 --> 00:45:55,570 what it's called. 676 00:45:55,570 --> 00:46:02,110 In flies, they name the genes based on the mutant phenotype. 677 00:46:02,110 --> 00:46:04,960 So if you mutate it, and it results in white-eyed flies, 678 00:46:04,960 --> 00:46:08,080 then they call it the white gene. 679 00:46:08,080 --> 00:46:10,540 All the males are going to have a functional 680 00:46:10,540 --> 00:46:13,210 copy of the white gene. 681 00:46:13,210 --> 00:46:16,030 And thus, all of these F1 flies are red-eyed. 682 00:46:21,490 --> 00:46:23,710 So now these siblings are mated. 683 00:46:23,710 --> 00:46:27,550 All the females are heterozygous for this gene. 684 00:46:27,550 --> 00:46:34,900 The males all have a functional copy of the gene. 685 00:46:34,900 --> 00:46:37,380 So they're going to make gametes that are either 686 00:46:37,380 --> 00:46:45,190 an X that's functional for this eye color or the Y chromosome. 687 00:46:45,190 --> 00:46:49,120 So now what you see is that all of the females 688 00:46:49,120 --> 00:46:52,738 are going to get this normal copy of the gene from dad, 689 00:46:52,738 --> 00:46:54,280 and thus, are going to have red eyes. 690 00:46:58,090 --> 00:47:00,370 Whereas half the males are going to get 691 00:47:00,370 --> 00:47:05,350 a functional copy from mom, and therefore, have red eyes. 692 00:47:05,350 --> 00:47:07,750 But the other half of the males are 693 00:47:07,750 --> 00:47:10,750 going to get this non-functional variant that 694 00:47:10,750 --> 00:47:13,570 can't produce red pigment, and therefore, 695 00:47:13,570 --> 00:47:16,240 are going to be white. 696 00:47:16,240 --> 00:47:20,020 So this here is your white class. 697 00:47:20,020 --> 00:47:23,770 And you can see because males only have one X chromosome, 698 00:47:23,770 --> 00:47:27,640 the only class of progeny that's going to be white-eyed here 699 00:47:27,640 --> 00:47:31,180 are those males that occur with a quarter frequency. 700 00:47:38,380 --> 00:47:42,010 One thing I want you to think about over the next couple 701 00:47:42,010 --> 00:47:42,610 days-- 702 00:47:42,610 --> 00:47:45,040 and I'll sort of take you through it 703 00:47:45,040 --> 00:47:47,050 at the beginning of next lecture-- 704 00:47:47,050 --> 00:47:52,180 is what would happen if you set up a reciprocal cross here? 705 00:47:52,180 --> 00:47:57,680 What if you mated red-eyed males to white-eyed females? 706 00:47:57,680 --> 00:48:01,960 And I want you to tell me what you expect would result. 707 00:48:01,960 --> 00:48:05,320 So my question for next Friday is, 708 00:48:05,320 --> 00:48:11,680 what if you took red-eyed males and mated it 709 00:48:11,680 --> 00:48:12,805 to white-eyed females? 710 00:48:17,950 --> 00:48:19,590 So I want you to think about this. 711 00:48:19,590 --> 00:48:23,740 And I want you to think how this is different from Mendel's 712 00:48:23,740 --> 00:48:24,260 experiment. 713 00:48:24,260 --> 00:48:28,990 What if you did a reciprocal cross for, let's say, 714 00:48:28,990 --> 00:48:31,330 the pea color? 715 00:48:31,330 --> 00:48:33,400 How would these two different crosses 716 00:48:33,400 --> 00:48:35,240 compare with each other? 717 00:48:35,240 --> 00:48:38,290 And we'll talk about that at the beginning of Friday's lecture. 718 00:48:38,290 --> 00:48:42,070 And we'll also talk about the first genetic map, 719 00:48:42,070 --> 00:48:45,260 which was actually created by an undergraduate. 720 00:48:45,260 --> 00:48:47,110 So stay tuned for that. 721 00:48:47,110 --> 00:48:49,110 See you on Friday.