1 00:00:00,040 --> 00:00:02,460 The following content is provided under a Creative 2 00:00:02,460 --> 00:00:03,870 Commons license. 3 00:00:03,870 --> 00:00:06,910 Your support will help MIT OpenCourseWare continue to 4 00:00:06,910 --> 00:00:10,560 offer high quality educational resources for free. 5 00:00:10,560 --> 00:00:13,460 To make a donation or view additional materials from 6 00:00:13,460 --> 00:00:19,290 hundreds of MIT courses, visit MIT OpenCourseWare at 7 00:00:19,290 --> 00:00:21,355 ocw.mit.edu. 8 00:00:21,355 --> 00:00:24,130 ERIC LANDER: Let's talk about what Mendel really did in his 9 00:00:24,130 --> 00:00:26,323 experiments. 10 00:00:26,323 --> 00:00:32,680 So section one, Mendel's experiments. 11 00:00:32,680 --> 00:00:35,900 Mendel did a lot of really cool things. 12 00:00:35,900 --> 00:00:39,940 The first thing he did was, in order to study heredity, that 13 00:00:39,940 --> 00:00:42,730 was his assignment as a monk-- go study heredity-- 14 00:00:42,730 --> 00:00:45,150 he had to get some material to work with. 15 00:00:45,150 --> 00:00:47,230 He decided to use peas. 16 00:00:47,230 --> 00:00:49,526 Why peas? 17 00:00:49,526 --> 00:00:52,700 Well, there are a lot of varieties of peas in the 18 00:00:52,700 --> 00:00:55,350 market, many different kinds of peas. 19 00:00:55,350 --> 00:00:56,980 And you could breed them together. 20 00:00:56,980 --> 00:00:59,110 There were tall peas, short peas, green peas, yellow peas, 21 00:00:59,110 --> 00:01:01,580 round peas, wrinkled peas, all kinds of peas that you could 22 00:01:01,580 --> 00:01:02,500 find in the market. 23 00:01:02,500 --> 00:01:04,510 They grew very well in the garden. 24 00:01:04,510 --> 00:01:06,990 And when you're done with the experiment, you could feed 25 00:01:06,990 --> 00:01:08,340 them to the monks. 26 00:01:08,340 --> 00:01:12,330 So the first thing he did was he got his material. 27 00:01:12,330 --> 00:01:16,490 And did he immediately start crossing his peas together? 28 00:01:16,490 --> 00:01:16,780 No. 29 00:01:16,780 --> 00:01:19,370 What did he do? 30 00:01:19,370 --> 00:01:22,695 AUDIENCE: [INAUDIBLE]. 31 00:01:22,695 --> 00:01:23,625 ERIC LANDER: Sorry? 32 00:01:23,625 --> 00:01:25,335 AUDIENCE: He grew them separately. 33 00:01:25,335 --> 00:01:27,160 ERIC LANDER: He first grew them separately. 34 00:01:27,160 --> 00:01:31,370 Because he wanted to see if he was going to study how traits 35 00:01:31,370 --> 00:01:34,580 were inherited, he first had to do the control experiment. 36 00:01:34,580 --> 00:01:37,860 He first had to show that if he took each variety of peas, 37 00:01:37,860 --> 00:01:39,790 they would breed true. 38 00:01:39,790 --> 00:01:45,160 So the first thing is, Mendel did controls. 39 00:01:45,160 --> 00:01:47,210 That's an important thing we learned from Mendel. 40 00:01:47,210 --> 00:01:49,130 He took round peas. 41 00:01:49,130 --> 00:01:50,820 He took wrinkled peas. 42 00:01:50,820 --> 00:01:53,100 And he bred them with themselves. 43 00:01:53,100 --> 00:01:54,390 And they always came out round. 44 00:01:54,390 --> 00:01:56,950 And he took wrinkled peas and he bred them with themselves. 45 00:01:56,950 --> 00:01:58,380 And they came out wrinkled. 46 00:01:58,380 --> 00:02:00,750 And if they hadn't always come out round or hadn't always 47 00:02:00,750 --> 00:02:03,760 come out wrinkled, it would've been a much harder experiment 48 00:02:03,760 --> 00:02:04,670 to interpret later. 49 00:02:04,670 --> 00:02:07,800 So that was incredibly important thing to do, was do 50 00:02:07,800 --> 00:02:11,090 the controls, round and wrinkled. 51 00:02:11,090 --> 00:02:15,270 Then, when he was satisfied that he had pure breeding or 52 00:02:15,270 --> 00:02:21,670 true breeding plants, then and only then did he do an 53 00:02:21,670 --> 00:02:22,920 experiment. 54 00:02:27,690 --> 00:02:29,060 What experiment did he do? 55 00:02:31,650 --> 00:02:32,620 You all know Mendel. 56 00:02:32,620 --> 00:02:35,700 The truth is, this is not like a surprise here. 57 00:02:35,700 --> 00:02:37,802 So what did he do? 58 00:02:37,802 --> 00:02:39,450 He crossed the round and the wrinkled. 59 00:02:42,440 --> 00:02:44,680 I'm trying to draw out the new things here, but some of the 60 00:02:44,680 --> 00:02:45,770 old ones you know. 61 00:02:45,770 --> 00:02:49,000 And when he crossed round and wrinkled-- 62 00:02:49,000 --> 00:02:52,780 We'll call this the F 0 generation. 63 00:02:52,780 --> 00:02:57,630 In the F 1 generation, what did he see? 64 00:03:00,624 --> 00:03:03,010 Round. 65 00:03:03,010 --> 00:03:04,200 You all know this. 66 00:03:04,200 --> 00:03:06,850 He saw all round. 67 00:03:06,850 --> 00:03:09,590 He didn't see puckered, slightly puckered or 68 00:03:09,590 --> 00:03:11,260 anything like that. 69 00:03:11,260 --> 00:03:12,840 He didn't see any wrinkles. 70 00:03:12,840 --> 00:03:15,740 They were all every bit as round as the rounds in the 71 00:03:15,740 --> 00:03:17,720 parental generation. 72 00:03:17,720 --> 00:03:19,770 That was an extremely important point, because of 73 00:03:19,770 --> 00:03:22,750 course, a competing theory of inheritance was blending 74 00:03:22,750 --> 00:03:25,450 inheritance, where the offspring would be 75 00:03:25,450 --> 00:03:26,250 intermediates. 76 00:03:26,250 --> 00:03:29,950 And the truth is almost every experiment that you do when 77 00:03:29,950 --> 00:03:32,680 you take plants and you cross them, or animals and you cross 78 00:03:32,680 --> 00:03:35,350 them, despite your biology textbook, shows blending 79 00:03:35,350 --> 00:03:35,930 inheritance. 80 00:03:35,930 --> 00:03:37,870 A tall plant and a short plant, you breed them. 81 00:03:37,870 --> 00:03:40,490 Almost always is a middle plant. 82 00:03:40,490 --> 00:03:41,420 But not for the peas. 83 00:03:41,420 --> 00:03:43,400 The peas were a beautiful system. 84 00:03:43,400 --> 00:03:46,650 And Mendel very lucky to have chosen it, because truth is, 85 00:03:46,650 --> 00:03:48,810 there was only one gene difference that was 86 00:03:48,810 --> 00:03:49,790 controlling these traits. 87 00:03:49,790 --> 00:03:52,080 If there'd been 10 genes controlling this, you'd get 88 00:03:52,080 --> 00:03:53,820 some blending, blah, blah, blah. 89 00:03:53,820 --> 00:03:56,720 But Mendel got a situation with really clean 90 00:03:56,720 --> 00:03:58,510 experimental data. 91 00:03:58,510 --> 00:04:00,970 The round was every bit as round. 92 00:04:00,970 --> 00:04:02,545 And so that said, no blending. 93 00:04:08,970 --> 00:04:11,980 Now what did he do? 94 00:04:11,980 --> 00:04:19,140 Next, what Mendel does is he crosses these round peas to 95 00:04:19,140 --> 00:04:19,959 themselves. 96 00:04:19,959 --> 00:04:21,640 He selfs them. 97 00:04:21,640 --> 00:04:23,770 So we're going to self the peas. 98 00:04:23,770 --> 00:04:26,180 The peas can be selfed. 99 00:04:26,180 --> 00:04:29,580 They have both male and female reproductive parts. 100 00:04:29,580 --> 00:04:33,210 And when he selfs them, they self pollinate. 101 00:04:33,210 --> 00:04:36,190 And what do they produce? 102 00:04:36,190 --> 00:04:37,440 Peas. 103 00:04:39,630 --> 00:04:40,190 That's good. 104 00:04:40,190 --> 00:04:41,440 They produce peas. 105 00:04:45,010 --> 00:04:48,000 And what does he notice? 106 00:04:48,000 --> 00:04:52,530 He notices that now they're not all round. 107 00:04:52,530 --> 00:04:54,530 Some of them are wrinkled. 108 00:04:54,530 --> 00:04:56,340 And the wrinkleds are every bit as wrinkled as the 109 00:04:56,340 --> 00:04:59,420 wrinkleds were in the parental generation F 0. 110 00:04:59,420 --> 00:05:01,310 And the round were every bit as round. 111 00:05:01,310 --> 00:05:04,590 So suddenly wrinkled had gone away. 112 00:05:04,590 --> 00:05:06,240 And what had happened? 113 00:05:06,240 --> 00:05:06,490 Sorry. 114 00:05:06,490 --> 00:05:09,380 Wrinkled had gone away in this generation. 115 00:05:09,380 --> 00:05:12,190 And now it had reappeared. 116 00:05:12,190 --> 00:05:15,735 The trait reappears. 117 00:05:21,240 --> 00:05:23,950 It's quantal. 118 00:05:23,950 --> 00:05:25,200 It's discrete. 119 00:05:27,240 --> 00:05:29,180 It's not blended out in any way. 120 00:05:29,180 --> 00:05:30,040 It's not blended. 121 00:05:30,040 --> 00:05:31,090 It's not imperfect. 122 00:05:31,090 --> 00:05:33,115 It's the same wrinkled that was there before. 123 00:05:36,480 --> 00:05:38,760 That's a big qualitative observation. 124 00:05:43,540 --> 00:05:46,030 This whole blending notion can't be right, at least for 125 00:05:46,030 --> 00:05:48,530 this experiment. 126 00:05:48,530 --> 00:05:50,920 Discreteness rules. 127 00:05:50,920 --> 00:05:55,270 So that was his experiment. 128 00:05:55,270 --> 00:06:00,800 Mendel could've written it up and said, wow, the traits 129 00:06:00,800 --> 00:06:01,920 don't blend. 130 00:06:01,920 --> 00:06:04,920 They're discrete. 131 00:06:04,920 --> 00:06:09,530 But Mendel, being an MIT kind of monk, went further. 132 00:06:09,530 --> 00:06:10,780 What did he do? 133 00:06:13,780 --> 00:06:14,130 Sorry? 134 00:06:14,130 --> 00:06:15,520 AUDIENCE: He repeated it. 135 00:06:15,520 --> 00:06:16,360 ERIC LANDER: He repeated it. 136 00:06:16,360 --> 00:06:17,770 And it still showed some rounds and 137 00:06:17,770 --> 00:06:19,850 wrinkleds and all that. 138 00:06:19,850 --> 00:06:22,830 But he was a very quantitative MIT monk. 139 00:06:22,830 --> 00:06:27,960 He counted them, which seems obvious, but ain't so obvious. 140 00:06:27,960 --> 00:06:29,790 He counted them. 141 00:06:29,790 --> 00:06:31,040 And what did he find? 142 00:06:33,860 --> 00:06:35,360 A fixed proportion? 143 00:06:35,360 --> 00:06:35,560 What? 144 00:06:35,560 --> 00:06:36,326 AUDIENCE: A ratio. 145 00:06:36,326 --> 00:06:38,041 ERIC LANDER: A ratio. 146 00:06:38,041 --> 00:06:39,805 AUDIENCE: Wasn't there 1:3? 147 00:06:39,805 --> 00:06:43,180 ERIC LANDER: 1:3 or 3:1 or something like that? 148 00:06:43,180 --> 00:06:44,650 No. 149 00:06:44,650 --> 00:06:46,170 No. 150 00:06:46,170 --> 00:06:47,550 Nope. 151 00:06:47,550 --> 00:06:50,320 No, he counted. 152 00:06:50,320 --> 00:06:52,170 He counted. 153 00:06:52,170 --> 00:07:00,500 And what he found was rounds: 5,474. 154 00:07:00,500 --> 00:07:07,310 Wrinkleds: 1,850. 155 00:07:07,310 --> 00:07:13,350 Ratio, not 3:1 at all. 156 00:07:13,350 --> 00:07:18,010 2.96:1. 157 00:07:18,010 --> 00:07:18,360 No, no, no. 158 00:07:18,360 --> 00:07:20,980 But you see, you say because your books all tell you 3:1, 159 00:07:20,980 --> 00:07:23,120 that it's obvious if you do that, you say, 160 00:07:23,120 --> 00:07:24,680 that must be 3:1. 161 00:07:24,680 --> 00:07:25,570 It not must be 3:1. 162 00:07:25,570 --> 00:07:26,770 It's 2.96:1. 163 00:07:26,770 --> 00:07:29,200 And if you do it again, you might get 2.87:1. 164 00:07:29,200 --> 00:07:33,210 And it actually takes quite an imagination to say, it's 165 00:07:33,210 --> 00:07:36,070 trying to be 3. 166 00:07:36,070 --> 00:07:37,290 Just think about it. 167 00:07:37,290 --> 00:07:38,670 You come to this experiment and you say, it's 168 00:07:38,670 --> 00:07:40,890 trying to be 3. 169 00:07:40,890 --> 00:07:43,240 That's a separate leap and an important leap. 170 00:07:43,240 --> 00:07:44,320 He counted. 171 00:07:44,320 --> 00:07:47,200 And he got numbers, 2.96:1. 172 00:07:47,200 --> 00:07:50,740 And he got other numbers. 173 00:07:50,740 --> 00:07:56,930 He then, as you've done so quickly, made a hypothesis. 174 00:07:56,930 --> 00:08:04,350 That hypothesis was that, in fact, this was trying to be 175 00:08:04,350 --> 00:08:10,180 3:1, that it quote "wanted to be 3:1." It was near 3:1. 176 00:08:10,180 --> 00:08:13,050 And that really the reason it was trying 177 00:08:13,050 --> 00:08:16,260 to be 3:1 was because-- 178 00:08:16,260 --> 00:08:19,220 Well, there was a pretty nice explanation here. 179 00:08:19,220 --> 00:08:23,900 His cool explanation was, the round plants and the wrinkled 180 00:08:23,900 --> 00:08:27,130 plants, well he made up a model. 181 00:08:27,130 --> 00:08:31,810 These guys had two particles of inheritance, big R big R, 182 00:08:31,810 --> 00:08:33,820 little r little r. 183 00:08:33,820 --> 00:08:37,010 When you cross them together, these guys were 184 00:08:37,010 --> 00:08:39,530 big R, little r. 185 00:08:39,530 --> 00:08:45,820 And when you self them, if you randomly chose one particle 186 00:08:45,820 --> 00:08:52,310 from the sperm and one particle from the egg, ovule, 187 00:08:52,310 --> 00:08:59,910 you would have big R, big R, big R, little r, little r, big 188 00:08:59,910 --> 00:09:04,970 R, and little r, little r, all as possibilities. 189 00:09:04,970 --> 00:09:11,050 And that these guys, big R, big R, they would be round. 190 00:09:11,050 --> 00:09:12,890 Why would they be round? 191 00:09:12,890 --> 00:09:16,130 Well because that's what the parental generation here was. 192 00:09:16,130 --> 00:09:20,710 The little r little r, they would be wrinkled. 193 00:09:20,710 --> 00:09:23,230 Because that's the parental generation there. 194 00:09:23,230 --> 00:09:27,530 And these guys that have one of each, what would they be? 195 00:09:27,530 --> 00:09:33,240 Round, because we saw that in the F1 generation, one of each 196 00:09:33,240 --> 00:09:35,260 makes it round. 197 00:09:35,260 --> 00:09:38,345 So we had a model, a hypothesis, a model. 198 00:09:44,030 --> 00:09:46,190 Pretty cool. 199 00:09:46,190 --> 00:09:50,480 You can come up with this model by saying, the 200 00:09:50,480 --> 00:09:53,840 contribution from the male, the contribution from the 201 00:09:53,840 --> 00:10:00,550 female, this is the male gametes, the female gametes. 202 00:10:00,550 --> 00:10:03,350 You get this nice little thing sometimes referred to as a 203 00:10:03,350 --> 00:10:05,080 Punnett square. 204 00:10:05,080 --> 00:10:06,670 Although he didn't use Punnett squares. 205 00:10:06,670 --> 00:10:08,120 And Punnett wasn't born yet. 206 00:10:14,690 --> 00:10:16,360 Now what do you do? 207 00:10:16,360 --> 00:10:18,960 Mendel went out and got experimental material. 208 00:10:18,960 --> 00:10:20,490 He did controls. 209 00:10:20,490 --> 00:10:22,090 He did an experiment. 210 00:10:22,090 --> 00:10:23,200 He counted. 211 00:10:23,200 --> 00:10:27,380 He then made this creative leap to say, I see something 212 00:10:27,380 --> 00:10:28,710 cool going on. 213 00:10:28,710 --> 00:10:31,290 Integers are what's going on. 214 00:10:31,290 --> 00:10:34,110 And made up a model. 215 00:10:34,110 --> 00:10:35,440 What does a scientist do at that point? 216 00:10:38,750 --> 00:10:40,500 Sorry? 217 00:10:40,500 --> 00:10:40,950 Oh come on. 218 00:10:40,950 --> 00:10:43,940 In this modern world, if you got a result this cool, what 219 00:10:43,940 --> 00:10:45,620 would you be doing? 220 00:10:45,620 --> 00:10:45,930 Sorry? 221 00:10:45,930 --> 00:10:46,646 AUDIENCE: Publish it. 222 00:10:46,646 --> 00:10:47,930 ERIC LANDER: Publish it right? 223 00:10:47,930 --> 00:10:50,410 You're going to get out there quickly and publish it. 224 00:10:50,410 --> 00:10:56,760 Mendel whips off an email to Nature in London, saying-- 225 00:10:56,760 --> 00:10:59,160 Or whatever the 1865 emails. 226 00:10:59,160 --> 00:11:00,390 Actually it wasn't Nature. 227 00:11:00,390 --> 00:11:02,220 It gets published in the Proceedings of the Royal 228 00:11:02,220 --> 00:11:03,710 Society of Brun. 229 00:11:03,710 --> 00:11:04,790 But forgive me. 230 00:11:04,790 --> 00:11:06,440 I'll use Nature, OK. 231 00:11:06,440 --> 00:11:08,590 So he whips off an email to Nature, which is what we do 232 00:11:08,590 --> 00:11:11,600 today, telling the editor, we have this really cool result. 233 00:11:11,600 --> 00:11:13,120 I think it'll be of broad interest to 234 00:11:13,120 --> 00:11:14,620 the readers of Nature. 235 00:11:14,620 --> 00:11:16,380 We're going to try to send you a paper next week, 236 00:11:16,380 --> 00:11:17,860 et cetera, et cetera. 237 00:11:17,860 --> 00:11:18,650 Are you interested? 238 00:11:18,650 --> 00:11:19,240 They write back, oh yeah. 239 00:11:19,240 --> 00:11:22,780 We'd love to see your paper Gregor. 240 00:11:22,780 --> 00:11:24,840 And Mendel whips together a paper. 241 00:11:27,720 --> 00:11:31,102 What happens when Mendel whips together this paper and it 242 00:11:31,102 --> 00:11:33,990 goes off to London, to Nature, the offices of Nature? 243 00:11:33,990 --> 00:11:34,976 What does Nature do with it? 244 00:11:34,976 --> 00:11:39,930 They just set it and type and say, here it is? 245 00:11:39,930 --> 00:11:42,920 What's the scientific process? 246 00:11:42,920 --> 00:11:44,670 Peer review. 247 00:11:44,670 --> 00:11:46,525 Before you go print this thing, you've got to send it 248 00:11:46,525 --> 00:11:49,710 out to some other scientists as anonymous reviewers and 249 00:11:49,710 --> 00:11:52,220 say, we've received this paper, this correspondence 250 00:11:52,220 --> 00:11:58,990 from Brother Mendel in Moravia. 251 00:11:58,990 --> 00:12:01,960 Would you review it for the journal Nature and tell us 252 00:12:01,960 --> 00:12:03,980 your candid opinion? 253 00:12:03,980 --> 00:12:05,290 And they write it up. 254 00:12:05,290 --> 00:12:06,510 And they send it back to Nature. 255 00:12:06,510 --> 00:12:09,860 And Nature makes a decision whether to publish the paper. 256 00:12:09,860 --> 00:12:11,110 So you're the reviewers. 257 00:12:14,130 --> 00:12:15,380 Should we publish Mendel's paper? 258 00:12:20,740 --> 00:12:21,990 Who says yes? 259 00:12:24,150 --> 00:12:26,910 Who says no? 260 00:12:26,910 --> 00:12:29,392 Why no? 261 00:12:29,392 --> 00:12:30,766 AUDIENCE: He needs more examples. 262 00:12:30,766 --> 00:12:31,880 ERIC LANDER: Needs more examples. 263 00:12:31,880 --> 00:12:32,710 So you're right. 264 00:12:32,710 --> 00:12:34,020 One lousy trait. 265 00:12:34,020 --> 00:12:36,060 Mendel actually had seven traits in the paper. 266 00:12:36,060 --> 00:12:38,730 It turns out I didn't tell you them all, green and yellow, 267 00:12:38,730 --> 00:12:39,650 and tall and short. 268 00:12:39,650 --> 00:12:40,750 And they're all in the paper. 269 00:12:40,750 --> 00:12:42,810 He actually has seven separate examples that 270 00:12:42,810 --> 00:12:44,020 show the same thing. 271 00:12:44,020 --> 00:12:46,170 Should we publish it? 272 00:12:46,170 --> 00:12:48,770 Why not? 273 00:12:48,770 --> 00:12:50,280 It's just peas. 274 00:12:50,280 --> 00:12:52,860 Oh boy, you're churlish there. 275 00:12:52,860 --> 00:12:54,010 I mean, come on. 276 00:12:54,010 --> 00:12:55,220 It's peas. 277 00:12:55,220 --> 00:12:56,150 People eat a lot of peas. 278 00:12:56,150 --> 00:12:57,210 It's a result. 279 00:12:57,210 --> 00:12:58,920 It'll get others in the scientific community 280 00:12:58,920 --> 00:13:01,312 interested. 281 00:13:01,312 --> 00:13:03,630 AUDIENCE: Who are the peer reviewers? 282 00:13:03,630 --> 00:13:04,300 ERIC LANDER: You. 283 00:13:04,300 --> 00:13:05,700 I've assigned you as peer reviewers. 284 00:13:05,700 --> 00:13:07,600 I'm asking you, should we publish this thing? 285 00:13:07,600 --> 00:13:09,700 We got seven traits we're going to publish. 286 00:13:09,700 --> 00:13:10,340 And it's pretty cool. 287 00:13:10,340 --> 00:13:12,705 Nobody's ever reported this 3:1 ratio in this model. 288 00:13:12,705 --> 00:13:13,310 AUDIENCE: That's true. 289 00:13:13,310 --> 00:13:14,850 But I wasn't the peer reviewer back then. 290 00:13:14,850 --> 00:13:15,633 ERIC LANDER: You are now. 291 00:13:15,633 --> 00:13:16,620 AUDIENCE: Then yes, I would publish it. 292 00:13:16,620 --> 00:13:17,210 ERIC LANDER: You'd publish it. 293 00:13:17,210 --> 00:13:17,405 OK. 294 00:13:17,405 --> 00:13:18,210 He'd publish it. 295 00:13:18,210 --> 00:13:19,360 Because nobody's reported this. 296 00:13:19,360 --> 00:13:19,990 It's pretty cool. 297 00:13:19,990 --> 00:13:22,610 The model perfectly fits the data. 298 00:13:22,610 --> 00:13:22,990 Yes. 299 00:13:22,990 --> 00:13:24,316 AUDIENCE: It's got to make predictions. 300 00:13:24,316 --> 00:13:27,230 ERIC LANDER: It's going to make predictions. 301 00:13:27,230 --> 00:13:29,598 But the model fits the data. 302 00:13:29,598 --> 00:13:32,161 AUDIENCE: The model needs to make predictions [INAUDIBLE] 303 00:13:32,161 --> 00:13:32,394 data. 304 00:13:32,394 --> 00:13:34,370 ERIC LANDER: Are you saying that we made up the model 305 00:13:34,370 --> 00:13:35,490 after we saw the data? 306 00:13:35,490 --> 00:13:40,040 And that it's not a surprise that the model fits the data? 307 00:13:40,040 --> 00:13:41,240 Yeah, that's right, isn't it. 308 00:13:41,240 --> 00:13:42,380 That's a real problem. 309 00:13:42,380 --> 00:13:45,200 If you make up models after they fit the data, they tend 310 00:13:45,200 --> 00:13:46,450 to fit the data. 311 00:13:48,570 --> 00:13:49,890 Well they do. 312 00:13:49,890 --> 00:13:52,020 That's a real problem. 313 00:13:52,020 --> 00:13:55,900 So the reviewers write back to Mendel and say, Mendel-- this 314 00:13:55,900 --> 00:13:57,465 isn't actually how it happened, you understand. 315 00:13:57,465 --> 00:13:59,210 But anyway, they write back to Mendel. 316 00:13:59,210 --> 00:14:00,850 They write back to the journal Nature. 317 00:14:00,850 --> 00:14:03,240 And they anonymously say, we would like to see some 318 00:14:03,240 --> 00:14:06,380 predictions of this model to see if this is really true. 319 00:14:06,380 --> 00:14:08,660 And Nature writes back to Mendel. 320 00:14:08,660 --> 00:14:10,300 And the email says, could you just show us some 321 00:14:10,300 --> 00:14:11,730 predictions from this? 322 00:14:11,730 --> 00:14:14,310 So to help Mendel out, what predictions can we make? 323 00:14:22,940 --> 00:14:26,040 What surprising predictions could you make for Mendel's 324 00:14:26,040 --> 00:14:26,640 experiment? 325 00:14:26,640 --> 00:14:32,790 Well, this experiment, round by wrinkled, gives round, 326 00:14:32,790 --> 00:14:37,030 gives some rounds and some wrinkles, which we think are 327 00:14:37,030 --> 00:14:40,750 big R, big R, big R, little r little r, big R, 328 00:14:40,750 --> 00:14:42,340 little r, little r. 329 00:14:42,340 --> 00:14:47,840 And that this is big R, big R. How could we prove something's 330 00:14:47,840 --> 00:14:50,320 going on in this generation? 331 00:14:50,320 --> 00:14:51,670 AUDIENCE: Self them. 332 00:14:51,670 --> 00:14:53,000 ERIC LANDER: Self them. 333 00:14:53,000 --> 00:14:55,210 If we pick out a round and self it, 334 00:14:55,210 --> 00:14:56,460 what's going to happen? 335 00:14:58,880 --> 00:14:59,340 Sorry? 336 00:14:59,340 --> 00:15:01,116 AUDIENCE: It depends on which round. 337 00:15:01,116 --> 00:15:02,770 ERIC LANDER: So how do I know which round to pick. 338 00:15:02,770 --> 00:15:03,440 They all look the same. 339 00:15:03,440 --> 00:15:04,112 AUDIENCE: You just try all of them. 340 00:15:04,112 --> 00:15:05,060 ERIC LANDER: Try all of them. 341 00:15:05,060 --> 00:15:06,630 If I try to all of them, what am I going to see? 342 00:15:06,630 --> 00:15:09,540 AUDIENCE: You'll see some that only produce rounds. 343 00:15:09,540 --> 00:15:10,362 ERIC LANDER: Produce rounds. 344 00:15:10,362 --> 00:15:13,120 About what fraction of them will only produce rounds? 345 00:15:13,120 --> 00:15:14,310 1/3. 346 00:15:14,310 --> 00:15:16,460 And what fraction will produce rounds and wrinkleds? 347 00:15:16,460 --> 00:15:17,080 AUDIENCE: 2/3. 348 00:15:17,080 --> 00:15:18,180 ERIC LANDER: 2/3. 349 00:15:18,180 --> 00:15:19,110 We have a prediction. 350 00:15:19,110 --> 00:15:20,010 Thank you. 351 00:15:20,010 --> 00:15:21,885 The prediction is, test the rounds. 352 00:15:26,740 --> 00:15:31,280 And although we don't know which are which, 1/3 of them 353 00:15:31,280 --> 00:15:38,320 will give rise to only rounds, whereas 2/3 of them will give 354 00:15:38,320 --> 00:15:41,800 rise to our 3:1 ratio. 355 00:15:41,800 --> 00:15:44,090 That is a non-obvious prediction. 356 00:15:44,090 --> 00:15:47,850 If this model weren't right, it's very surprising if you 357 00:15:47,850 --> 00:15:50,480 would have nailed that prediction. 358 00:15:50,480 --> 00:15:51,800 Nice. 359 00:15:51,800 --> 00:15:53,420 What other predictions can you make? 360 00:15:53,420 --> 00:15:57,626 What other crosses could you set up to test it? 361 00:15:57,626 --> 00:15:59,896 AUDIENCE: Wrinkleds by wrinkleds. 362 00:15:59,896 --> 00:16:01,550 ERIC LANDER: The wrinkleds by themselves 363 00:16:01,550 --> 00:16:02,490 will only give wrinkles. 364 00:16:02,490 --> 00:16:03,700 And that's true. 365 00:16:03,700 --> 00:16:04,020 Bingo. 366 00:16:04,020 --> 00:16:05,030 So we're doing well. 367 00:16:05,030 --> 00:16:06,186 What else? 368 00:16:06,186 --> 00:16:07,644 AUDIENCE: Wrinkleds with rounds. 369 00:16:07,644 --> 00:16:09,330 ERIC LANDER: Wrinkleds with rounds. 370 00:16:09,330 --> 00:16:17,080 So I could take these three rounds here and I can cross 371 00:16:17,080 --> 00:16:19,410 them to wrinkleds. 372 00:16:19,410 --> 00:16:20,260 What'll happen here? 373 00:16:20,260 --> 00:16:23,900 If this was rounds, rounds over wrinkled, wrinkled, it's 374 00:16:23,900 --> 00:16:25,090 going to give rise to what? 375 00:16:25,090 --> 00:16:25,980 AUDIENCE: Rounds. 376 00:16:25,980 --> 00:16:27,960 ERIC LANDER: All rounds. 377 00:16:27,960 --> 00:16:32,436 But if this is round wrinkled, what would it give rise to? 378 00:16:32,436 --> 00:16:33,744 AUDIENCE: Half and half. 379 00:16:33,744 --> 00:16:35,680 ERIC LANDER: 50:50. 380 00:16:35,680 --> 00:16:38,890 Half and half. 381 00:16:38,890 --> 00:16:40,095 Now we're cooking. 382 00:16:40,095 --> 00:16:42,070 There are all these predictions that start 383 00:16:42,070 --> 00:16:45,750 dropping out, because your model tells you things you 384 00:16:45,750 --> 00:16:48,490 haven't yet seen. 385 00:16:48,490 --> 00:16:52,670 Mendel writes back and says, I did all the experiments. 386 00:16:52,670 --> 00:16:54,890 I did what the referees requested. 387 00:16:54,890 --> 00:16:56,200 The referees get the paper back. 388 00:16:56,200 --> 00:16:58,370 They say, yes indeed, Mendel's done the experiments. 389 00:16:58,370 --> 00:16:59,510 We recommend publication. 390 00:16:59,510 --> 00:17:01,060 Nature publishes it. 391 00:17:01,060 --> 00:17:03,320 They put out a press release and all that. 392 00:17:03,320 --> 00:17:06,280 Mendel's on the evening news, that kind of thing. 393 00:17:06,280 --> 00:17:08,740 It didn't really happen that way exactly. 394 00:17:08,740 --> 00:17:11,130 But anyway, you get the point. 395 00:17:11,130 --> 00:17:13,980 That's the process of doing science. 396 00:17:13,980 --> 00:17:15,150 It's a cool process. 397 00:17:15,150 --> 00:17:16,530 And it's a back and forth. 398 00:17:16,530 --> 00:17:18,869 And it's a process of convincing people, and you 399 00:17:18,869 --> 00:17:21,550 convince them by predictions. 400 00:17:21,550 --> 00:17:23,089 And you can think of the kinds of cool 401 00:17:23,089 --> 00:17:24,680 predictions you could make. 402 00:17:24,680 --> 00:17:26,780 And that's what's fun about working in a lab, is making 403 00:17:26,780 --> 00:17:27,900 those kind of predictions. 404 00:17:27,900 --> 00:17:31,400 Now all right. 405 00:17:31,400 --> 00:17:32,650 I need to give you a few definitions. 406 00:17:42,690 --> 00:17:43,940 A gene. 407 00:17:45,950 --> 00:17:49,510 When I refer to a gene for the moment, I mean a discrete 408 00:17:49,510 --> 00:17:54,100 factor of inheritance, discrete particle, factor of 409 00:17:54,100 --> 00:17:56,380 inheritance, something like that. 410 00:17:56,380 --> 00:17:59,730 Because geneticists early on had no idea what genes were. 411 00:17:59,730 --> 00:18:01,965 You know perfectly well a gene is a DNA sequence, 412 00:18:01,965 --> 00:18:04,230 blah blah blah blah. 413 00:18:04,230 --> 00:18:06,020 But it's useful to be able to think about 414 00:18:06,020 --> 00:18:07,580 a gene in the abstract. 415 00:18:07,580 --> 00:18:12,260 It's the thing that controls a particular inheritance of a 416 00:18:12,260 --> 00:18:14,410 particular trait. 417 00:18:14,410 --> 00:18:19,130 Variant forms of a gene, alternative forms of a gene, 418 00:18:19,130 --> 00:18:20,380 are called alleles. 419 00:18:24,410 --> 00:18:30,570 When I write big R, little r, they are alleles of the gene 420 00:18:30,570 --> 00:18:32,590 for roundness. 421 00:18:32,590 --> 00:18:36,500 Allele, from the Greek meaning other or alternative. 422 00:18:36,500 --> 00:18:47,690 When I write genotype, I mean the combination of alleles 423 00:18:47,690 --> 00:18:49,830 that an individual has. 424 00:18:49,830 --> 00:18:53,350 Like when I write big R, big R, that's a genotype. 425 00:18:53,350 --> 00:18:57,770 Or big R, little r, or little r, 426 00:18:57,770 --> 00:18:59,440 little r, that's a genotype. 427 00:19:02,020 --> 00:19:09,050 When I say the word phenotype, what do I mean? 428 00:19:09,050 --> 00:19:10,403 A trait, an appearance. 429 00:19:15,800 --> 00:19:19,440 What are the traits under discussion here? 430 00:19:19,440 --> 00:19:20,690 Round and wrinkled. 431 00:19:26,680 --> 00:19:28,400 Geneticists are like mathematicians. 432 00:19:28,400 --> 00:19:31,070 They're very precise about their words. 433 00:19:31,070 --> 00:19:35,130 Now comes the ones that people always have trouble with, 434 00:19:35,130 --> 00:19:41,080 dominant and recessive. 435 00:19:47,130 --> 00:20:08,146 Phenotype 1 is dominant to phenotype 2 if the-- 436 00:20:08,146 --> 00:20:09,396 Oops, sorry. 437 00:20:11,870 --> 00:20:14,870 I meant to add two words here. 438 00:20:14,870 --> 00:20:23,450 Heterozygote, homozygote, words you know as well. 439 00:20:23,450 --> 00:20:27,740 Heterozygote, having different alleles. 440 00:20:27,740 --> 00:20:31,440 Homozygote, having the same alleles. 441 00:20:31,440 --> 00:20:33,360 Different, same alleles. 442 00:20:33,360 --> 00:20:38,930 So a phenotype, phenotype 1 is dominant to phenotype 2 if the 443 00:20:38,930 --> 00:20:47,300 F1 heterozygote, the cross between them, has phenotype 1. 444 00:20:53,520 --> 00:20:57,100 Why did I write this in this wacky mathematical way? 445 00:20:57,100 --> 00:21:00,570 That says round is dominant to wrinkled if when I cross round 446 00:21:00,570 --> 00:21:04,110 to wrinkled, the offspring are round. 447 00:21:04,110 --> 00:21:06,870 So which is dominant, round or wrinkled? 448 00:21:06,870 --> 00:21:09,630 Which is dominant, big R, or little r? 449 00:21:09,630 --> 00:21:11,860 No. 450 00:21:11,860 --> 00:21:15,060 Big R is an allele. 451 00:21:15,060 --> 00:21:20,420 We said phenotypes are dominant, not alleles. 452 00:21:20,420 --> 00:21:23,230 We don't say big R is dominant to little r. 453 00:21:23,230 --> 00:21:25,940 We say round is dominant to wrinkled. 454 00:21:25,940 --> 00:21:27,300 Now this will bother you greatly. 455 00:21:27,300 --> 00:21:32,010 And it will bother about 95% of my biology colleagues. 456 00:21:32,010 --> 00:21:35,890 But geneticists who are careful use the word dominant 457 00:21:35,890 --> 00:21:39,200 and recessive to refer to phenotypes, not alleles. 458 00:21:39,200 --> 00:21:40,450 Why do I care? 459 00:21:43,330 --> 00:21:48,950 I care because big R, as a molecular allele, as a variant 460 00:21:48,950 --> 00:21:52,200 of a gene, might end up controlling three or five 461 00:21:52,200 --> 00:21:54,120 different traits. 462 00:21:54,120 --> 00:21:57,490 Some of the traits that big R controls could be dominant. 463 00:21:57,490 --> 00:22:00,240 Some of them could be recessive. 464 00:22:00,240 --> 00:22:05,390 Sickle cell anemia, there's a sickle cell mutation. 465 00:22:05,390 --> 00:22:09,210 Is that recessive or dominant? 466 00:22:09,210 --> 00:22:12,750 Sickle cell anemia is a recessive 467 00:22:12,750 --> 00:22:15,400 trait, a recessive phenotype. 468 00:22:15,400 --> 00:22:19,430 But sickle cell trait, the tendency for blood cells to 469 00:22:19,430 --> 00:22:24,240 sickle at low oxygen tension, is a dominant phenotype. 470 00:22:24,240 --> 00:22:27,740 The allele that causes sickle cell anemia causes a recessive 471 00:22:27,740 --> 00:22:31,600 trait, anemia, and a dominant trait that can be measured in 472 00:22:31,600 --> 00:22:34,240 heterzygotes. 473 00:22:34,240 --> 00:22:35,150 You'll forget this. 474 00:22:35,150 --> 00:22:36,400 Everyone will forget this. 475 00:22:36,400 --> 00:22:39,830 But I've at least told you once that alleles could 476 00:22:39,830 --> 00:22:42,480 control multiple phenotypes and do control multiple 477 00:22:42,480 --> 00:22:42,870 phenotypes. 478 00:22:42,870 --> 00:22:45,770 And that's why geneticists obsess about using the words 479 00:22:45,770 --> 00:22:49,330 recessive and dominant to refer to the phenotype, not 480 00:22:49,330 --> 00:22:50,980 the genotype. 481 00:22:50,980 --> 00:22:52,920 I've made my plea. 482 00:22:52,920 --> 00:22:54,880 Like all of my colleagues in the biology department, you 483 00:22:54,880 --> 00:22:56,520 will continue to misuse the word. 484 00:22:56,520 --> 00:22:58,600 But there's a better chance you'll get it right because 485 00:22:58,600 --> 00:23:00,460 I've made my little stand here. 486 00:23:00,460 --> 00:23:02,775 Recessive is the opposite of this. 487 00:23:02,775 --> 00:23:04,050 Good. 488 00:23:04,050 --> 00:23:06,220 This is mostly to say, geneticists try to think 489 00:23:06,220 --> 00:23:07,950 carefully about their words. 490 00:23:07,950 --> 00:23:11,240 Those are the definitions. 491 00:23:11,240 --> 00:23:14,130 You should be able to use the words gene, allele, genotype, 492 00:23:14,130 --> 00:23:18,200 heterzygote, homozygote, phenotype, dominant, recessive 493 00:23:18,200 --> 00:23:19,450 in a good way.