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These are the user uploaded subtitles that are being translated: 0 00:00:02,325 --> 00:00:14,650 PROFESSOR: Section 3, Linkage Maps, where our hero Alfred Sturtevant, the 1 00:00:14,650 --> 00:00:23,100 19-year-old junior at Columbia, takes home the data and figures out why the 2 00:00:23,100 --> 00:00:26,140 Chromosome Theory really truly is right. 3 00:00:26,140 --> 00:00:37,410 So he starts out saying black and vestigial, right up there in 4 00:00:37,410 --> 00:00:39,300 the cross we did. 5 00:00:39,300 --> 00:00:40,390 How far apart were they? 6 00:00:40,390 --> 00:00:41,970 What was the recombination frequency? 7 00:00:41,970 --> 00:00:43,180 STUDENT: 17%. 8 00:00:43,180 --> 00:00:48,230 PROFESSOR: 17%, so let's put them down on the map and write-- 9 00:00:48,230 --> 00:00:49,195 I'll move it over. 10 00:00:49,195 --> 00:00:49,980 We'll just put it there. 11 00:00:49,980 --> 00:00:54,340 17%. 12 00:00:54,340 --> 00:00:58,200 Now he goes to some other piece of data in the lab and he says, oh, yeah, 13 00:00:58,200 --> 00:01:04,080 someone did a cross with vestigial and that eye color thing I showed you over 14 00:01:04,080 --> 00:01:07,380 there, cinnabar, an eye color mutant. 15 00:01:07,380 --> 00:01:12,870 And what they found was that vestigial and cinnabar had 8% 16 00:01:12,870 --> 00:01:16,160 recombination frequency. 17 00:01:16,160 --> 00:01:19,340 He said, where should I put it on the map? 18 00:01:19,340 --> 00:01:22,560 Cinnabar is 8% away from vestigial. 19 00:01:25,320 --> 00:01:27,776 Where should it go on the map? 20 00:01:27,776 --> 00:01:29,240 STUDENT: Depends how far it is from it. 21 00:01:29,240 --> 00:01:31,010 PROFESSOR: Depends on which side it's on. 22 00:01:31,010 --> 00:01:37,500 So maybe cinnabar is over here, or maybe cinnabar is over here, but 23 00:01:37,500 --> 00:01:44,780 either way it's 8% to the left or 8% to the right of vestigial, if this 24 00:01:44,780 --> 00:01:46,930 Chromosome Theory is right. 25 00:01:46,930 --> 00:01:47,440 Which is it? 26 00:01:47,440 --> 00:01:50,543 How do we know whether it's to the right or to the left? 27 00:01:50,543 --> 00:01:52,395 [INTERPOSING VOICES] 28 00:01:52,395 --> 00:01:55,820 PROFESSOR: Ah, testable predictions. 29 00:01:55,820 --> 00:01:59,110 For the first time in all this stuff, we're hearing some testable 30 00:01:59,110 --> 00:02:00,270 predictions. 31 00:02:00,270 --> 00:02:02,130 Testable prediction-- 32 00:02:02,130 --> 00:02:11,300 if it's over here on the left and it's 8% away, 8% over here, what should the 33 00:02:11,300 --> 00:02:12,150 distance be-- 34 00:02:12,150 --> 00:02:15,710 we'll call that cinnabar, because that's what it was-- 35 00:02:15,710 --> 00:02:18,130 what should the distance be between black and cinnabar? 36 00:02:18,130 --> 00:02:18,822 STUDENT: 9%. 37 00:02:18,822 --> 00:02:20,072 PROFESSOR: It should be 9%. 38 00:02:22,900 --> 00:02:28,890 But what if instead cinnabar is over here? 39 00:02:28,890 --> 00:02:30,560 How far will black be away? 40 00:02:30,560 --> 00:02:31,412 STUDENT: 25. 41 00:02:31,412 --> 00:02:34,370 PROFESSOR: It'll be the 17 plus 8. 42 00:02:34,370 --> 00:02:43,060 It'll be 17 plus 8. 43 00:02:43,060 --> 00:02:45,880 He checks the data. 44 00:02:45,880 --> 00:02:52,640 Black and vestigial are 17, vestigial to cinnabar is 8, black 45 00:02:52,640 --> 00:02:54,360 to cinnabar is 9. 46 00:02:56,960 --> 00:03:04,500 He had two choices, and it turned out that this looks like it's the map-- 47 00:03:04,500 --> 00:03:09,776 9, 8, 17. 48 00:03:09,776 --> 00:03:11,810 Now he goes further. 49 00:03:11,810 --> 00:03:13,030 He gets another cross. 50 00:03:13,030 --> 00:03:15,800 There's a mutant called lobe. 51 00:03:15,800 --> 00:03:20,290 Lobe has 5% recombination away from vestigial. 52 00:03:20,290 --> 00:03:23,140 Where do you want to stick it? 53 00:03:23,140 --> 00:03:25,240 One side or the other. 54 00:03:25,240 --> 00:03:33,290 If it's over here at 5%, the lobe mutant-- 55 00:03:33,290 --> 00:03:36,200 give me a testable prediction. 56 00:03:36,200 --> 00:03:38,260 Cinnabar to lobe will be how much? 57 00:03:38,260 --> 00:03:38,992 STUDENT: 13. 58 00:03:38,992 --> 00:03:41,222 PROFESSOR: 13. 59 00:03:41,222 --> 00:03:43,730 It is. 60 00:03:43,730 --> 00:03:46,912 How far will it be from black to lobe? 61 00:03:46,912 --> 00:03:47,884 STUDENT: 22. 62 00:03:47,884 --> 00:03:48,900 PROFESSOR: How much? 63 00:03:48,900 --> 00:03:49,790 STUDENT: 22. 64 00:03:49,790 --> 00:03:53,350 PROFESSOR: 22. 65 00:03:53,350 --> 00:03:54,600 It is. 66 00:03:56,690 --> 00:03:58,430 This is a very good all-nighter. 67 00:03:58,430 --> 00:04:01,300 He's sitting there drawing things. 68 00:04:01,300 --> 00:04:03,890 Try another one over here, curved wing. 69 00:04:06,950 --> 00:04:10,200 It's 3 away from lobed. 70 00:04:10,200 --> 00:04:14,480 If it's on that side, then this will be 8. 71 00:04:14,480 --> 00:04:18,130 That will be 16, et cetera, et cetera. 72 00:04:18,130 --> 00:04:23,160 Every new gene that I drop into that map ends up making lots of testable 73 00:04:23,160 --> 00:04:24,990 predictions. 74 00:04:24,990 --> 00:04:28,300 And just the opposite of all the other stuff that has been going on, those 75 00:04:28,300 --> 00:04:32,670 testable predictions are being tested and they're turning out to be right. 76 00:04:32,670 --> 00:04:33,920 That is so cool. 77 00:04:37,570 --> 00:04:41,900 Alfred Sturtevant is saying the idea that these things lie on a line makes 78 00:04:41,900 --> 00:04:45,440 these testable predictions of all those distances are going to be, and 79 00:04:45,440 --> 00:04:48,420 they're all checking out. 80 00:04:48,420 --> 00:04:50,550 He does one other thing. 81 00:04:50,550 --> 00:04:55,730 He says this involves pair wise. 82 00:04:55,730 --> 00:05:03,500 These are two factor crosses, crosses that just involve two genes 83 00:05:03,500 --> 00:05:03,950 simultaneously. 84 00:05:03,950 --> 00:05:05,800 They're like we've been drawing over there. 85 00:05:05,800 --> 00:05:12,950 It's just pairwise testing of particular pairs of genes. 86 00:05:12,950 --> 00:05:16,905 What about three factor crosses? 87 00:05:22,750 --> 00:05:25,675 What do I mean by a three factor cross? 88 00:05:25,675 --> 00:05:28,520 Well, I'm going to forget about black and cinnabar and vestigial and all 89 00:05:28,520 --> 00:05:30,190 those sort of things for the moment. 90 00:05:30,190 --> 00:05:34,370 And I'm just going to make it very simple and say, suppose I had a cross 91 00:05:34,370 --> 00:05:44,200 where in the F1 I had a, b, c, plus, plus, plus. 92 00:05:44,200 --> 00:05:51,500 I'm going to cross it to a, b, c, a, b, c, and I'm going to look at the 93 00:05:51,500 --> 00:05:55,110 possible gametes that could come out in a three factor cross. 94 00:05:55,110 --> 00:05:59,510 How many possible gametes can come out in a three factor cross? 95 00:05:59,510 --> 00:06:02,530 I've got two choices at the first locus-- 96 00:06:02,530 --> 00:06:05,320 at the first gene, I've got two choices at the next gene and I've got 97 00:06:05,320 --> 00:06:06,340 two choices and the next gene. 98 00:06:06,340 --> 00:06:08,870 That makes eight possible choices, right. 99 00:06:08,870 --> 00:06:10,850 So let's actually write those down. 100 00:06:10,850 --> 00:06:11,370 Let's see. 101 00:06:11,370 --> 00:06:15,420 If this theory is right, this Chromosome Theory is right, I've got 102 00:06:15,420 --> 00:06:23,910 my a, b, c, I've got my plus, plus, plus, and crossovers could occur. 103 00:06:23,910 --> 00:06:27,806 Maybe there's no crossovers or maybe there's a crossover here or a 104 00:06:27,806 --> 00:06:29,550 crossover there. 105 00:06:29,550 --> 00:06:30,140 Oh, I don't know. 106 00:06:30,140 --> 00:06:38,430 Let's for the sake of argument, say this is 10% recombination here and 10% 107 00:06:38,430 --> 00:06:42,870 recombination here just in my simple example. 108 00:06:42,870 --> 00:06:43,860 Well, what are the possibilities? 109 00:06:43,860 --> 00:06:46,450 I could have no recombinations at all. 110 00:06:46,450 --> 00:06:52,190 If no recombination occurs, no crossing over occurs, then what kind 111 00:06:52,190 --> 00:06:55,420 of gametes can I get out of that? 112 00:06:55,420 --> 00:07:02,725 I could get a, b, c, or I could get plus plus plus. 113 00:07:05,240 --> 00:07:17,800 Now I could have one recombination that separates a away. 114 00:07:21,870 --> 00:07:22,880 So what could I get there? 115 00:07:22,880 --> 00:07:27,470 For a recombination occurs that separates from b and c, what kind of 116 00:07:27,470 --> 00:07:29,791 gametes could there be? 117 00:07:29,791 --> 00:07:36,970 a plus plus or plus b c will be the kinds of gametes that I could get. a 118 00:07:36,970 --> 00:07:43,920 plus plus or plus b c, and one recombination can do it. 119 00:07:43,920 --> 00:07:48,930 What's the chance of one recombination occurring, a recombination occurring 120 00:07:48,930 --> 00:07:50,600 here but not here? 121 00:07:50,600 --> 00:07:53,330 What's the chance of recombination here? 122 00:07:53,330 --> 00:07:54,330 We said 10%. 123 00:07:54,330 --> 00:07:56,460 What's the chance of no recombination here? 124 00:07:56,460 --> 00:07:57,310 STUDENT: 90. 125 00:07:57,310 --> 00:07:58,670 PROFESSOR: 90%. 126 00:07:58,670 --> 00:08:07,530 So that's going to be 10% times 90%, so that means 9% of the time 127 00:08:07,530 --> 00:08:08,935 we might see that. 128 00:08:08,935 --> 00:08:10,470 Let's just check out one over here. 129 00:08:10,470 --> 00:08:12,790 What's the chance there's no recombination here and no 130 00:08:12,790 --> 00:08:13,740 recombination here? 131 00:08:13,740 --> 00:08:13,990 STUDENT: 90 times 90. 132 00:08:13,990 --> 00:08:22,780 PROFESSOR: 90 times 90, 90% times 90% is 81%. 133 00:08:22,780 --> 00:08:28,370 Let's try this recombination now over here that separates away c. 134 00:08:28,370 --> 00:08:29,920 What are the possible gametes? 135 00:08:29,920 --> 00:08:35,695 We'll have recombination separating c. 136 00:08:38,520 --> 00:08:47,025 What do we get, a b plus or plus b c-- 137 00:08:47,025 --> 00:08:49,960 I'm sorry, or plus plus c. 138 00:08:49,960 --> 00:08:51,020 There we go. 139 00:08:51,020 --> 00:08:52,892 And what's the probability of that occurring? 140 00:08:52,892 --> 00:08:53,836 STUDENT: 90%. 141 00:08:53,836 --> 00:09:02,090 PROFESSOR: 90% times 10% equals 9%. 142 00:09:02,090 --> 00:09:08,030 But can I ever get a gamete where b has been separated away from little a 143 00:09:08,030 --> 00:09:09,022 and little c? 144 00:09:09,022 --> 00:09:10,320 STUDENT: Two recombinations. 145 00:09:10,320 --> 00:09:14,130 PROFESSOR: It takes two recombinations, not one recombination. 146 00:09:14,130 --> 00:09:16,420 Two won't do, so one won't do it. 147 00:09:16,420 --> 00:09:17,600 You need two recombinations. 148 00:09:17,600 --> 00:09:21,000 You need this event and that event. 149 00:09:23,910 --> 00:09:34,080 Two recombinations, two recombination events, and then you 150 00:09:34,080 --> 00:09:35,670 can separate b away. 151 00:09:35,670 --> 00:09:40,530 But because b is in the middle, it takes two, and you're going to get 152 00:09:40,530 --> 00:09:44,650 plus b plus, a plus c. 153 00:09:44,650 --> 00:09:48,370 And what's the chance of two recombinations? 154 00:09:48,370 --> 00:10:00,510 10% times 10% equals 1%. 155 00:10:00,510 --> 00:10:05,690 One of the three is very hard to separate away from the others because 156 00:10:05,690 --> 00:10:08,900 it takes two crossovers if it's in the middle. 157 00:10:08,900 --> 00:10:12,700 That is a pretty cool testable prediction that based on the two 158 00:10:12,700 --> 00:10:19,170 factor distances and the map of who's in the middle, you can predict that 159 00:10:19,170 --> 00:10:22,550 one of them is going to be very much harder to separate from the others 160 00:10:22,550 --> 00:10:24,340 because it takes two crossovers. 161 00:10:24,340 --> 00:10:28,620 And when you look at the data, that's what you see. 162 00:10:31,930 --> 00:10:35,560 The sun rises over Manhattan. 163 00:10:35,560 --> 00:10:42,380 Bleary Alfred Sturtevant realizes that the Chromosome Theory checks out. 164 00:10:42,380 --> 00:10:45,730 It makes amazing testable predictions of this whole thing. 165 00:10:49,410 --> 00:10:53,400 Sturtevant writes it up and it becomes one of the most 166 00:10:53,400 --> 00:10:56,520 famous papers in genetics. 167 00:10:56,520 --> 00:10:59,870 Why is it such a famous paper in genetics? 168 00:10:59,870 --> 00:11:03,020 Let's just flip to a fly map here. 169 00:11:03,020 --> 00:11:05,850 This is an example of the fruit fly genetic map. 170 00:11:05,850 --> 00:11:09,900 This has only got a teeny fraction of what's on the fruit fly genetic map. 171 00:11:09,900 --> 00:11:14,980 You've got vermilion and scalloped wings and here's cinnabar and 172 00:11:14,980 --> 00:11:17,900 vestigial and lobed curved and black body. 173 00:11:17,900 --> 00:11:20,480 Right over here is where we've been working on the map. 174 00:11:20,480 --> 00:11:23,090 And all of these different traits are there. 175 00:11:23,090 --> 00:11:28,220 This is, like, way cool, this map that he's produced and that scientists 176 00:11:28,220 --> 00:11:34,670 throughout the rest and rest of the century produce. 177 00:11:34,670 --> 00:11:37,860 We've got a question for you now about recombination frequency. 178 00:11:37,860 --> 00:11:41,030 Try answering this one to be sure that you understand how 179 00:11:41,030 --> 00:11:42,280 recombination works. 13672

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