1 00:00:00,840 --> 00:00:02,820 [Lecturer] Hello, and welcome to the third 2 00:00:02,820 --> 00:00:04,890 and final lecture in module two. 3 00:00:04,890 --> 00:00:08,100 Congratulations for making it this far. (chuckles) 4 00:00:08,100 --> 00:00:10,320 Hopefully your head's not spinning too much, 5 00:00:10,320 --> 00:00:12,870 and the information is starting to soak 6 00:00:12,870 --> 00:00:17,580 in a little reinforced through the reading in mostly 7 00:00:17,580 --> 00:00:22,350 in the textbook chapter that excerpts 8 00:00:22,350 --> 00:00:24,300 from the textbook chapter that I wrote. 9 00:00:25,260 --> 00:00:28,530 There isn't that much information in the textbook 10 00:00:28,530 --> 00:00:30,300 for the class on this material. 11 00:00:30,300 --> 00:00:31,410 There's just a few pages, 12 00:00:31,410 --> 00:00:34,500 and in my opinion, it can be a little bit confusing 13 00:00:34,500 --> 00:00:36,300 because it's lacking the detail. 14 00:00:36,300 --> 00:00:37,710 I think it's necessary for you 15 00:00:37,710 --> 00:00:39,810 to understand what they're trying to convey there. 16 00:00:39,810 --> 00:00:43,210 So hopefully you're getting that through the text 17 00:00:44,251 --> 00:00:45,663 in the posted reading, 18 00:00:46,830 --> 00:00:50,100 and the lectures are serving to reinforce 19 00:00:50,100 --> 00:00:52,950 that and to provide you some more detail 20 00:00:52,950 --> 00:00:55,170 and some more color on all of that. 21 00:00:55,170 --> 00:00:58,140 And just, again, remember, this isn't the end 22 00:00:58,140 --> 00:00:59,010 of this material. 23 00:00:59,010 --> 00:01:00,510 We're going to keep coming back to it. 24 00:01:00,510 --> 00:01:03,030 So if it hasn't all fully soaked in 25 00:01:03,030 --> 00:01:06,930 with you yet, just know it will, it absolutely will. 26 00:01:06,930 --> 00:01:09,990 This is the beginning of this semester for this course, 27 00:01:09,990 --> 00:01:12,390 and it will keep coming back up 28 00:01:12,390 --> 00:01:14,490 and in different ways, in different contexts. 29 00:01:14,490 --> 00:01:18,060 And I think, you know, through continued exposure 30 00:01:18,060 --> 00:01:20,520 and exposure in different ways, it will really start 31 00:01:20,520 --> 00:01:22,290 to soak in and not only soak in, 32 00:01:22,290 --> 00:01:25,470 but also start to become clear how this is relevant 33 00:01:25,470 --> 00:01:27,150 for you and for your practice. 34 00:01:27,150 --> 00:01:30,030 But once you have the basics down, then the rest 35 00:01:30,030 --> 00:01:33,000 of it will really start to fall into place. 36 00:01:33,000 --> 00:01:36,393 So let's start talking about the central dogma. 37 00:01:37,650 --> 00:01:41,490 Comes up to the question of what does DNA actually do? 38 00:01:41,490 --> 00:01:43,770 And why is it really that important? 39 00:01:43,770 --> 00:01:46,350 DNA is like the blueprint for life. 40 00:01:46,350 --> 00:01:49,080 It gives instructions for all cells to make all 41 00:01:49,080 --> 00:01:51,840 of their proteins that they will ever make. 42 00:01:51,840 --> 00:01:54,600 So at the very moment of conception, when an egg 43 00:01:54,600 --> 00:01:57,630 and sperm fuse, and you have the full complement of DNA 44 00:01:57,630 --> 00:02:01,350 for an individual that contains all of the instructions 45 00:02:01,350 --> 00:02:03,540 that single cell will need to turn 46 00:02:03,540 --> 00:02:06,730 into an adult fully functioning human being 47 00:02:08,070 --> 00:02:09,990 after development and all of 48 00:02:09,990 --> 00:02:12,390 that, it basically provides all the instructions 49 00:02:14,493 --> 00:02:16,470 that any and all cells that form from 50 00:02:16,470 --> 00:02:18,900 that one original cell will ever need 51 00:02:18,900 --> 00:02:21,180 to make all the proteins it will ever need. 52 00:02:21,180 --> 00:02:24,030 To me, that's pretty astounding to think about. 53 00:02:24,030 --> 00:02:27,150 At the very beginning, all the information is there 54 00:02:27,150 --> 00:02:29,010 and it will happen and it will develop 55 00:02:29,010 --> 00:02:30,560 if given the right environment. 56 00:02:32,670 --> 00:02:34,980 A region of DNA strand that gives the instructions 57 00:02:34,980 --> 00:02:37,830 for making a single protein is called a gene. 58 00:02:37,830 --> 00:02:39,300 So this is how we're defining gene. 59 00:02:39,300 --> 00:02:42,120 It is the unit of inheritance, 60 00:02:42,120 --> 00:02:44,130 and one gene equals the instructions 61 00:02:44,130 --> 00:02:47,295 for making one single protein. 62 00:02:47,295 --> 00:02:50,640 And this is just to a small recap 63 00:02:50,640 --> 00:02:53,310 from what I think was covered in the previous lecture 64 00:02:53,310 --> 00:02:56,811 as well, but just want to reinforce here, one gene, the way 65 00:02:56,811 --> 00:03:01,811 a gene is defined really is that it is a sequence of DNA 66 00:03:03,090 --> 00:03:05,820 and that sequence will provide the instructions 67 00:03:05,820 --> 00:03:07,893 for making a single protein. 68 00:03:08,970 --> 00:03:10,620 Proteins perform virtually all functions 69 00:03:10,620 --> 00:03:12,150 within the cells, tissues, and organs. 70 00:03:12,150 --> 00:03:13,890 And we talked about this already, 71 00:03:13,890 --> 00:03:15,810 but just want to reinforce that's the case. 72 00:03:15,810 --> 00:03:18,900 You have lots of different types of proteins, 73 00:03:18,900 --> 00:03:21,900 of course, just giving a couple examples of proteins 74 00:03:21,900 --> 00:03:24,720 that you can think of insulin, keratin, 75 00:03:24,720 --> 00:03:26,310 neurotransmitter receptors. 76 00:03:26,310 --> 00:03:29,610 I mean, there are thousands and thousands 77 00:03:29,610 --> 00:03:30,930 and thousands of different proteins, 78 00:03:30,930 --> 00:03:32,970 and they all perform very specialized 79 00:03:32,970 --> 00:03:34,533 and distinct functions. 80 00:03:35,730 --> 00:03:40,350 So we have about 25,000 genes in the human genome. 81 00:03:40,350 --> 00:03:42,450 So, but we do actually have more 82 00:03:42,450 --> 00:03:44,040 than 25,000 different proteins. 83 00:03:44,040 --> 00:03:44,910 So how does that work? 84 00:03:44,910 --> 00:03:47,280 You probably are wondering, and rightly so. 85 00:03:47,280 --> 00:03:50,040 Well, again, this is the majority rule 86 00:03:50,040 --> 00:03:51,630 versus the exception rule. 87 00:03:51,630 --> 00:03:55,560 And if we're going on the majority here, the majority 88 00:03:55,560 --> 00:03:59,070 of genes will code for one single protein. 89 00:03:59,070 --> 00:04:02,610 However, proteins can also form different structures 90 00:04:02,610 --> 00:04:05,160 by taking subunits of proteins. 91 00:04:05,160 --> 00:04:07,410 I mean, there's a lot of complicated biology 92 00:04:07,410 --> 00:04:10,440 that can happen, and biochemistry that can happen. 93 00:04:10,440 --> 00:04:11,970 Modifications of proteins 94 00:04:11,970 --> 00:04:15,510 often occur, which can give them distinct functions. 95 00:04:15,510 --> 00:04:19,050 But in general, what we're talking about here in general is 96 00:04:19,050 --> 00:04:21,990 that a single gene will give the instructions 97 00:04:21,990 --> 00:04:25,263 for the cell to properly form one protein. 98 00:04:26,490 --> 00:04:29,160 Genes are made up of bases, as we talked about 99 00:04:29,160 --> 00:04:32,580 in the last lecture, adenine, thymine, cytosine, guanine. 100 00:04:32,580 --> 00:04:36,690 Your four buddies, A, T, C, and G. 101 00:04:36,690 --> 00:04:38,310 So genes are made up of these bases 102 00:04:38,310 --> 00:04:39,417 in a particular sequence. 103 00:04:39,417 --> 00:04:41,940 And the sequence is an arrangement of bases, 104 00:04:41,940 --> 00:04:44,940 like a word made up of specific letters. 105 00:04:44,940 --> 00:04:46,410 So if you're thinking about this, 106 00:04:46,410 --> 00:04:50,250 here's a different metaphor for you, you can think 107 00:04:50,250 --> 00:04:52,800 of the bases as the letters, 108 00:04:52,800 --> 00:04:55,320 and they kind of are, makes it a little simpler 109 00:04:55,320 --> 00:04:57,480 to think of it this way because we represent them 110 00:04:57,480 --> 00:05:00,060 as single letters, but you can think of them as letters, 111 00:05:00,060 --> 00:05:04,163 and you could think of the gene as either a word 112 00:05:04,163 --> 00:05:06,840 or a sentence, say for example. 113 00:05:06,840 --> 00:05:10,830 And that's made up of the right sequence, the right order 114 00:05:10,830 --> 00:05:11,663 of letters. 115 00:05:11,663 --> 00:05:15,420 If something is in the wrong order or missing something 116 00:05:15,420 --> 00:05:18,630 or has something added to it, it would be a different word, 117 00:05:18,630 --> 00:05:19,770 it would be a different sentence. 118 00:05:19,770 --> 00:05:21,570 It would have completely different meaning. 119 00:05:21,570 --> 00:05:23,730 Very similarly here, the sequence, the order 120 00:05:23,730 --> 00:05:26,324 in which As Ts, Cs, and Gs appear 121 00:05:26,324 --> 00:05:30,450 in a gene, it will affect the instructions 122 00:05:30,450 --> 00:05:33,123 for that formation of that particular protein. 123 00:05:35,460 --> 00:05:38,100 So DNA has a pretty cushy job. 124 00:05:38,100 --> 00:05:42,780 You know, it itself doesn't actually do all that much. 125 00:05:42,780 --> 00:05:45,300 It's like the boss, it sends out instructions 126 00:05:45,300 --> 00:05:47,400 from its cushy office in the nucleus. 127 00:05:47,400 --> 00:05:48,630 It's sitting in the nucleus. 128 00:05:48,630 --> 00:05:52,500 It sends out instructions into the cytoplasm 129 00:05:52,500 --> 00:05:54,660 of the cell, and it provides instructions 130 00:05:54,660 --> 00:05:57,180 for other things, you know, other components 131 00:05:57,180 --> 00:05:59,160 to actually do the work of making proteins. 132 00:05:59,160 --> 00:06:00,570 And the proteins are the workhorses. 133 00:06:00,570 --> 00:06:02,855 So they go out and they actually do all the work 134 00:06:02,855 --> 00:06:05,349 in the cell while the DNA sort of sits there 135 00:06:05,349 --> 00:06:09,150 in the nucleus, very protected, which it really has 136 00:06:09,150 --> 00:06:12,570 to be protected because the sequence is quite precious given 137 00:06:12,570 --> 00:06:15,540 that it, the sequence has to be copied with high fidelity 138 00:06:15,540 --> 00:06:18,510 from one generation to the next thousands 139 00:06:18,510 --> 00:06:19,710 and thousands of times over, 140 00:06:19,710 --> 00:06:21,632 if you consider how many times your cells divide 141 00:06:21,632 --> 00:06:22,980 within your body. 142 00:06:22,980 --> 00:06:24,810 So it has to be protected, it's very special, 143 00:06:24,810 --> 00:06:26,820 very precious information. 144 00:06:26,820 --> 00:06:29,245 And also it's gonna be passed on to the next generation 145 00:06:29,245 --> 00:06:32,100 and the next one after that, and the next one after that. 146 00:06:32,100 --> 00:06:35,277 So it needs to be protected and it needs to remain safe. 147 00:06:35,277 --> 00:06:38,876 And in order to do that, it's kept very distinctly 148 00:06:38,876 --> 00:06:41,501 within the nucleus of the cell. 149 00:06:41,501 --> 00:06:43,860 But in order for it to function, it has 150 00:06:43,860 --> 00:06:44,960 to send out these messages 151 00:06:44,960 --> 00:06:49,290 into the cell cytoplasm to tell it how 152 00:06:49,290 --> 00:06:52,293 to basically make all the proteins it needs to make. 153 00:06:53,280 --> 00:06:55,370 The sequence of a gene is copied from the DNA 154 00:06:55,370 --> 00:06:59,940 in the nucleus into a molecule called mRNA. 155 00:06:59,940 --> 00:07:04,940 This stands for M for messenger. RNA is ribonucleic acid. 156 00:07:04,980 --> 00:07:07,743 So this is messenger ribonucleic acid. 157 00:07:08,820 --> 00:07:11,910 The mRNA is transported out of the nucleus 158 00:07:11,910 --> 00:07:15,240 to the protein assembly line where it is used 159 00:07:15,240 --> 00:07:18,330 to instruct how ribosomes assemble proteins. 160 00:07:18,330 --> 00:07:19,800 This process is called translation. 161 00:07:19,800 --> 00:07:22,956 So the first process of copying the DNA 162 00:07:22,956 --> 00:07:27,480 of a gene, the sequence of a gene to mRNA. 163 00:07:27,480 --> 00:07:31,290 So making a copy of it doesn't actually do anything negative 164 00:07:31,290 --> 00:07:33,540 or any way affect the DNA strand itself. 165 00:07:33,540 --> 00:07:35,430 It's just simply making copy, like going 166 00:07:35,430 --> 00:07:38,880 to the library, taking a book, making a photocopy of it. 167 00:07:38,880 --> 00:07:42,190 You know, say like, I think I used this metaphor 168 00:07:43,140 --> 00:07:47,067 in the textbook chapter that that's posted for you to read, 169 00:07:47,067 --> 00:07:50,280 but it's like a reference book at a library, 170 00:07:50,280 --> 00:07:52,620 if you remember what libraries are. (laughs) 171 00:07:52,620 --> 00:07:54,630 Again, I keep using these metaphors and I'm thinking, well, 172 00:07:54,630 --> 00:07:57,930 we don't really use corded telephones and nobody really goes 173 00:07:57,930 --> 00:08:00,510 to the library anymore, but okay, let's assume 174 00:08:00,510 --> 00:08:03,420 that you still go to the library and you want 175 00:08:03,420 --> 00:08:05,880 to look up some information in a reference book 176 00:08:05,880 --> 00:08:07,530 and say something that you can't check out 177 00:08:07,530 --> 00:08:09,900 of the library because it's too precious. 178 00:08:09,900 --> 00:08:11,760 What you could do instead is take it 179 00:08:11,760 --> 00:08:14,040 to the photocopier machine, sit it down 180 00:08:14,040 --> 00:08:17,430 on the photocopier, scan it, take a copy of that, 181 00:08:17,430 --> 00:08:20,370 and that's what you would take out of the library with you. 182 00:08:20,370 --> 00:08:22,620 Let's imagine for a second that the nucleus is 183 00:08:22,620 --> 00:08:26,850 like the library, where in order to get the information 184 00:08:26,850 --> 00:08:30,960 from the nucleus or the library, you go into it, you take it 185 00:08:30,960 --> 00:08:33,150 and you scan a copy, you make a copy 186 00:08:33,150 --> 00:08:35,880 without harming the reference book, which in this case, 187 00:08:35,880 --> 00:08:37,020 in this metaphor would be 188 00:08:37,020 --> 00:08:40,350 like DNA, you're not harming it, you're not destroying it, 189 00:08:40,350 --> 00:08:41,670 you're not taking a part of it, 190 00:08:41,670 --> 00:08:44,900 you're just simply making a copy of it, take a copy of it. 191 00:08:44,900 --> 00:08:49,110 In this case, the copy, the photocopy would be the mRNA. 192 00:08:49,110 --> 00:08:52,020 So it's just a duplicate, essentially 193 00:08:52,020 --> 00:08:53,463 of the DNA sequence. 194 00:08:54,645 --> 00:08:56,880 It can actually leave the nucleus 195 00:08:56,880 --> 00:08:59,130 because it's just a temporary thing, 196 00:08:59,130 --> 00:09:04,130 like it's just a temporary stretch of nucleic acids, 197 00:09:04,174 --> 00:09:08,160 that matches the sequence of that particular gene. 198 00:09:08,160 --> 00:09:10,770 So it can leave the nucleus, that's no problem. 199 00:09:10,770 --> 00:09:12,330 It does, it leaves the nucleus. 200 00:09:12,330 --> 00:09:15,810 So that would be like you taking your photocopies home. 201 00:09:15,810 --> 00:09:16,643 And let's say 202 00:09:16,643 --> 00:09:18,360 in this particular case, it was a reference book 203 00:09:18,360 --> 00:09:22,260 for how to build a bicycle. 204 00:09:22,260 --> 00:09:25,110 You make your copy from the reference book 205 00:09:25,110 --> 00:09:26,730 on how to build a bicycle. 206 00:09:26,730 --> 00:09:28,890 You take that out with you back home. 207 00:09:28,890 --> 00:09:30,780 In this case, going home would be sort of 208 00:09:30,780 --> 00:09:32,730 like leaving the nucleus and going 209 00:09:32,730 --> 00:09:37,368 into the cell cytoplasm where you'll use your tools, say, 210 00:09:37,368 --> 00:09:39,870 your toolbox, your toolkit 211 00:09:39,870 --> 00:09:43,350 for building a bicycle would be really like the ribosomes. 212 00:09:43,350 --> 00:09:46,830 They're going to read the instructions that copied 213 00:09:46,830 --> 00:09:48,180 in this case, like mRNA, 214 00:09:48,180 --> 00:09:50,700 that ribosomes are gonna read the mRNA, that copy 215 00:09:50,700 --> 00:09:53,430 of the sequence, and that's going to tell them how 216 00:09:53,430 --> 00:09:57,690 to assemble that specific protein properly. 217 00:09:57,690 --> 00:10:01,788 Copying the sequence to mRNA is called transcription. 218 00:10:01,788 --> 00:10:05,950 And when the copy or the mRNA is read, 219 00:10:05,950 --> 00:10:09,960 and that instruction is used for making protein 220 00:10:09,960 --> 00:10:13,263 or protein synthesis, that process is called translation. 221 00:10:15,780 --> 00:10:16,650 Let's take a quick peek 222 00:10:16,650 --> 00:10:18,780 at proteins you're probably quite familiar 223 00:10:18,780 --> 00:10:23,340 with certain proteins that are very clinically relevant, 224 00:10:23,340 --> 00:10:26,970 but proteins are made up of a chain of amino acids. 225 00:10:26,970 --> 00:10:30,540 So they're also like a long chain that what we're looking 226 00:10:30,540 --> 00:10:34,590 at here, in this case, this is like a schematic 227 00:10:34,590 --> 00:10:37,440 of a structure using like molecular structure 228 00:10:37,440 --> 00:10:39,300 of a particular protein. 229 00:10:39,300 --> 00:10:42,390 And it is a long chain, 230 00:10:42,390 --> 00:10:44,280 but you can see this doesn't look like a long chain. 231 00:10:44,280 --> 00:10:46,170 This is kind of bunched up and curled up, 232 00:10:46,170 --> 00:10:48,240 and that's absolutely true. 233 00:10:48,240 --> 00:10:51,240 It's formed as a long chain of amino acids. 234 00:10:51,240 --> 00:10:52,650 One attached to the other, attached 235 00:10:52,650 --> 00:10:54,240 to the other, attached to the other. 236 00:10:54,240 --> 00:10:56,383 But then after that, each amino acid has 237 00:10:56,383 --> 00:11:00,180 a very unique chemical structure such that 238 00:11:00,180 --> 00:11:03,660 after the long chain has formed, the protein will start 239 00:11:03,660 --> 00:11:06,990 to fold in on itself and it will form grooves 240 00:11:06,990 --> 00:11:09,663 and it will form very specific shape 241 00:11:09,663 --> 00:11:13,200 to it, which is necessary, completely necessary 242 00:11:13,200 --> 00:11:15,240 for its proper function. 243 00:11:15,240 --> 00:11:16,073 In the case 244 00:11:16,073 --> 00:11:20,940 of proteins structure absolutely determines function. 245 00:11:20,940 --> 00:11:22,500 Structure determines function 246 00:11:22,500 --> 00:11:25,440 and structure of a protein is determined 247 00:11:25,440 --> 00:11:28,380 by its amino acid sequence. 248 00:11:28,380 --> 00:11:31,140 So if we're looking at the schematic 249 00:11:31,140 --> 00:11:34,680 of a protein, say this is basically just showing you a bunch 250 00:11:34,680 --> 00:11:38,610 of different amino acids that are all connected together 251 00:11:38,610 --> 00:11:41,490 as a long chain then folded up on itself. 252 00:11:41,490 --> 00:11:42,690 So protein is just made up 253 00:11:42,690 --> 00:11:45,630 of individual units called amino acids 254 00:11:45,630 --> 00:11:48,540 that interact and fold up on itself 255 00:11:48,540 --> 00:11:51,180 to form the final structure of the protein. 256 00:11:51,180 --> 00:11:54,510 And that structure determines the protein's function. 257 00:11:54,510 --> 00:11:56,670 Its ability to do what it needs to do 258 00:11:56,670 --> 00:12:00,000 within a cell, which is so important. 259 00:12:00,000 --> 00:12:04,634 This is where disease happens because proteins are critical 260 00:12:04,634 --> 00:12:07,560 for every function in the human body. 261 00:12:07,560 --> 00:12:10,110 You can't think of one where a protein isn't necessary 262 00:12:10,110 --> 00:12:12,090 or used in some particular way. 263 00:12:12,090 --> 00:12:16,170 So if a protein happens to have the wrong amino acid 264 00:12:16,170 --> 00:12:18,990 in the wrong place and it can't fold properly, can't form 265 00:12:18,990 --> 00:12:20,220 the right structure, guess what? 266 00:12:20,220 --> 00:12:22,710 It's not gonna have the right function, it's not going 267 00:12:22,710 --> 00:12:24,240 to function properly. 268 00:12:24,240 --> 00:12:26,823 So then that leads to disease. 269 00:12:29,340 --> 00:12:31,590 Okay, let's take a look over here. 270 00:12:31,590 --> 00:12:34,770 So we've talked about amino acids must be the correct ones, 271 00:12:34,770 --> 00:12:36,180 and then the correct order for the protein 272 00:12:36,180 --> 00:12:38,130 to function properly or at all. 273 00:12:38,130 --> 00:12:39,240 Even a single change 274 00:12:39,240 --> 00:12:41,823 in amino acid can disrupt the protein's function. 275 00:12:42,720 --> 00:12:46,410 There are 20 different amino acids, proteins vary greatly 276 00:12:46,410 --> 00:12:48,000 in length, but median length 277 00:12:48,000 --> 00:12:53,000 of a protein is 361 amino acids, but take my word for it. 278 00:12:53,301 --> 00:12:55,530 And they can go from, (chuckles) you know, very short 279 00:12:55,530 --> 00:13:00,390 to really, really long 361 is just the median length 280 00:13:00,390 --> 00:13:02,163 of proteins. 281 00:13:05,460 --> 00:13:08,100 Central dogma, this is a weird phrase, right? 282 00:13:08,100 --> 00:13:09,840 When are we're talking about central dogma, again, 283 00:13:09,840 --> 00:13:11,370 it sounds very philosophical 284 00:13:11,370 --> 00:13:14,490 and maybe even a little religious or something, 285 00:13:14,490 --> 00:13:19,307 but actually, it's not, it is a really key insight 286 00:13:20,820 --> 00:13:22,440 into molecular biology 287 00:13:22,440 --> 00:13:26,610 that is sounds simple when we think about it now, 288 00:13:26,610 --> 00:13:29,160 but was so impactful in the way 289 00:13:29,160 --> 00:13:31,260 that we understand really everything 290 00:13:31,260 --> 00:13:33,420 that functions on a molecular level. 291 00:13:33,420 --> 00:13:36,330 It was first stated by Francis Crick in 1958. 292 00:13:36,330 --> 00:13:38,220 As you can recall, Francis Crick was part 293 00:13:38,220 --> 00:13:40,410 of the Watson and Crick duo 294 00:13:40,410 --> 00:13:43,740 that originally described the structure of DNA. 295 00:13:43,740 --> 00:13:46,200 So it was a very busy guy. 296 00:13:46,200 --> 00:13:48,687 And in 1958, he stated 297 00:13:48,687 --> 00:13:50,910 for the first time that, hey, you know what? 298 00:13:50,910 --> 00:13:55,910 Maybe this is the way DNA functions DNA to RNA to protein. 299 00:13:57,300 --> 00:13:58,710 And what do I mean by that? 300 00:13:58,710 --> 00:14:01,920 Well, this just means this is the flow of information. 301 00:14:01,920 --> 00:14:06,450 So DNA is copied into RNA, RNA provides instructions 302 00:14:06,450 --> 00:14:09,570 for making protein, it always goes this direction. 303 00:14:09,570 --> 00:14:14,310 It always goes DNA to RNA to protein. 304 00:14:14,310 --> 00:14:16,740 You never have protein going back 305 00:14:16,740 --> 00:14:21,390 and informing the instruction of RNA and RNA going back 306 00:14:21,390 --> 00:14:24,690 and somehow affecting the structure of DNA. 307 00:14:24,690 --> 00:14:27,480 Never, never, never, always. 308 00:14:27,480 --> 00:14:28,950 And this is, hey, this is one 309 00:14:28,950 --> 00:14:30,780 of the times I can actually say always (laughs) 310 00:14:30,780 --> 00:14:32,610 and I don't have to say, well, except, and 311 00:14:32,610 --> 00:14:37,610 from all we really understand now, it does always go DNA 312 00:14:38,460 --> 00:14:40,890 to RNA to protein. 313 00:14:40,890 --> 00:14:42,930 Part of the reason for that is what I've been saying, 314 00:14:42,930 --> 00:14:46,890 what I was saying before, which is that DNA is precious. 315 00:14:46,890 --> 00:14:49,020 That's the material that gets passed on. 316 00:14:49,020 --> 00:14:52,110 That's the unit of inheritance from generation 317 00:14:52,110 --> 00:14:54,720 to generation within your own body, 318 00:14:54,720 --> 00:14:56,670 from cell division to cell division. 319 00:14:56,670 --> 00:14:58,826 That is the part that is always going 320 00:14:58,826 --> 00:15:01,800 to be there and always going to be the same. 321 00:15:01,800 --> 00:15:03,960 So we need to protect it. 322 00:15:03,960 --> 00:15:06,600 So it always goes DNA, instructing RNA, 323 00:15:06,600 --> 00:15:09,240 instructing protein formation. 324 00:15:09,240 --> 00:15:13,353 DNA is copied into a complimentary strand of messenger, RNA. 325 00:15:14,400 --> 00:15:17,070 The mRNA is used by ribosomes 326 00:15:17,070 --> 00:15:19,860 in the cytoplasm outside of the nucleus to tell it 327 00:15:19,860 --> 00:15:22,410 to assemble which amino acids and in what order 328 00:15:22,410 --> 00:15:24,210 to properly form a protein. 329 00:15:24,210 --> 00:15:28,140 And remember the right order of amino acids determines the 330 00:15:28,140 --> 00:15:30,750 right function of that protein. 331 00:15:30,750 --> 00:15:35,640 Really, really critical. And again, this is the order. 332 00:15:35,640 --> 00:15:40,290 So step one, this is called transcription. 333 00:15:40,290 --> 00:15:43,350 Step two, this is called translation. 334 00:15:43,350 --> 00:15:44,430 Always goes in that order. 335 00:15:44,430 --> 00:15:47,100 Transcription first, translation second, you have 336 00:15:47,100 --> 00:15:51,840 to make the copy before you can use it to make the protein. 337 00:15:51,840 --> 00:15:53,880 I just wanna make sure that it's very clear here 338 00:15:53,880 --> 00:15:56,460 because I know this is a common misunderstanding 339 00:15:56,460 --> 00:15:58,620 that can happen when we're talking about 340 00:15:58,620 --> 00:16:00,150 DNA to RNA to protein. 341 00:16:00,150 --> 00:16:05,150 DNA does not become RNA, DNA is used to make a copy 342 00:16:07,470 --> 00:16:11,700 that is housed in a molecule called RNA. 343 00:16:11,700 --> 00:16:13,983 RNA is a separate molecule from DNA. 344 00:16:13,983 --> 00:16:18,210 It's just used to make a copy of the DNA. 345 00:16:18,210 --> 00:16:20,790 The RNA does not become protein. 346 00:16:20,790 --> 00:16:23,640 The RNA is used as an instruction, 347 00:16:23,640 --> 00:16:24,473 and we'll talk about 348 00:16:24,473 --> 00:16:26,880 that when we talk about specifics of translation. 349 00:16:26,880 --> 00:16:29,640 But RNA is used to provide directions for how 350 00:16:29,640 --> 00:16:30,930 to properly make proteins. 351 00:16:30,930 --> 00:16:32,880 Proteins are made up of amino acids. 352 00:16:32,880 --> 00:16:35,940 Amino acids are very, very different 353 00:16:35,940 --> 00:16:39,093 from nucleotides, which make up RNA and DNA. 354 00:16:40,080 --> 00:16:42,353 Just wanna make sure that that's pretty clear. 355 00:16:43,500 --> 00:16:45,060 All right, let's take a quick peek 356 00:16:45,060 --> 00:16:47,340 at a schematic of the cell. 357 00:16:47,340 --> 00:16:49,980 And when we're talking about transcription and translation. 358 00:16:49,980 --> 00:16:52,260 DNA in the nucleus, we all know this, 359 00:16:52,260 --> 00:16:53,790 we all love this fact, right? 360 00:16:53,790 --> 00:16:57,210 DNA in the nucleus of the cell, transcription happens. 361 00:16:57,210 --> 00:16:59,880 This is, we'll talk about this in more detail, 362 00:16:59,880 --> 00:17:01,560 but you can start to think of it 363 00:17:01,560 --> 00:17:04,110 as basically one of the two strands. 364 00:17:04,110 --> 00:17:06,150 Remember DNA's double stranded, right? 365 00:17:06,150 --> 00:17:08,167 One of the two strands is used 366 00:17:08,167 --> 00:17:12,990 to make a copy of it, a complimentary copy of it. 367 00:17:12,990 --> 00:17:14,820 Remember what complimentary means? 368 00:17:14,820 --> 00:17:17,070 A binding to T, binding to G. 369 00:17:17,070 --> 00:17:18,357 There is a slight exception here, 370 00:17:18,357 --> 00:17:21,240 and we will talk about that in just a moment. 371 00:17:21,240 --> 00:17:24,360 But basically this is what happens during the transcription. 372 00:17:24,360 --> 00:17:28,680 mRNA is formed as a copy of DNA. 373 00:17:28,680 --> 00:17:31,680 This is completely different molecule does not destroy 374 00:17:31,680 --> 00:17:36,300 in any way, mark or is any way detrimental 375 00:17:36,300 --> 00:17:38,823 to DNA, it's simply copying it. 376 00:17:39,900 --> 00:17:42,390 The mRNA, which is a very short strand compared 377 00:17:42,390 --> 00:17:44,970 to really, really, really long DNA strands, 378 00:17:44,970 --> 00:17:46,980 this is not showing it to scale. 379 00:17:46,980 --> 00:17:49,770 DNA strand, as we've talked about, you know, can be really, 380 00:17:49,770 --> 00:17:51,453 really, it's really, really long. 381 00:17:52,410 --> 00:17:54,060 mRNA is just the length 382 00:17:54,060 --> 00:17:56,850 of the gene, just the length of one gene. 383 00:17:56,850 --> 00:17:58,560 That's the length of the mRNA 384 00:17:58,560 --> 00:18:00,360 because you only need the one gene. 385 00:18:00,360 --> 00:18:03,690 'Cause one gene instructs the formation of one protein. 386 00:18:03,690 --> 00:18:06,809 So mRNA is formed, mRNA is free 387 00:18:06,809 --> 00:18:11,809 to leave the nucleus while DNA is stuck in the nucleus. 388 00:18:12,720 --> 00:18:16,067 mRNA can leave 'cause it's really a short strand 389 00:18:16,067 --> 00:18:18,540 and it also has certain modifications 390 00:18:18,540 --> 00:18:20,460 to it, the DNA does not have, which allows it 391 00:18:20,460 --> 00:18:23,553 to leave the nucleus, so mRNA leaves the nucleus. 392 00:18:24,660 --> 00:18:27,570 So this first step here is called transcription, 393 00:18:27,570 --> 00:18:32,040 making a copy of a sequence of one gene from one 394 00:18:32,040 --> 00:18:37,040 of the strands of DNA into mRNA. 395 00:18:37,170 --> 00:18:40,230 That's transcription, mRNA leaves the nucleus. 396 00:18:40,230 --> 00:18:43,470 And here's where we start to talk about translation. 397 00:18:43,470 --> 00:18:45,480 So how do you get that message 398 00:18:45,480 --> 00:18:48,030 of the DNA sequence which was copied 399 00:18:48,030 --> 00:18:50,790 into mRNA, into protein? 400 00:18:50,790 --> 00:18:52,560 Well, the cell has come up 401 00:18:52,560 --> 00:18:54,840 with a really cool way to do this. 402 00:18:54,840 --> 00:18:59,490 It's actually using code, a code of information 403 00:18:59,490 --> 00:19:03,450 that's housed in the specific order of the bases. 404 00:19:03,450 --> 00:19:06,150 Remember the bases are As, Ts, Cs, and Gs? 405 00:19:06,150 --> 00:19:08,730 The specific order of those which can be found 406 00:19:08,730 --> 00:19:11,980 in the sequence is used and is decoded 407 00:19:13,200 --> 00:19:17,700 to determine the specific amino acid sequence. 408 00:19:17,700 --> 00:19:19,110 What do I mean by that? 409 00:19:19,110 --> 00:19:20,880 Well, the cell has come up 410 00:19:20,880 --> 00:19:23,637 with a specific code where it knows 411 00:19:23,637 --> 00:19:26,100 and it does this in sets of three. 412 00:19:26,100 --> 00:19:27,540 So if you think about it, I don't know, 413 00:19:27,540 --> 00:19:32,340 if you as a kid or you know, if you have children, 414 00:19:32,340 --> 00:19:33,173 if you've ever done this 415 00:19:33,173 --> 00:19:35,940 with them, where you could get like a decoder ring 416 00:19:35,940 --> 00:19:40,940 and you know, you can take the hidden message 417 00:19:41,160 --> 00:19:42,990 and figure out what it actually means. 418 00:19:42,990 --> 00:19:46,740 You know, so this symbol equals A, this symbol equals B, 419 00:19:46,740 --> 00:19:47,910 this symbol equals C. 420 00:19:47,910 --> 00:19:49,560 And you know, you can kind of figure it out 421 00:19:49,560 --> 00:19:51,630 and piece it together, you're breaking a code. 422 00:19:51,630 --> 00:19:53,790 That's exactly what the cell is doing. 423 00:19:53,790 --> 00:19:56,010 The cell is taking this, the specific order 424 00:19:56,010 --> 00:20:00,293 of As, Ts, Cs and Gs and it knows this particular sequence 425 00:20:00,293 --> 00:20:05,280 of bases equals this particular amino acid. 426 00:20:05,280 --> 00:20:09,843 This other sequence of bases equals this other amino acid. 427 00:20:11,220 --> 00:20:14,700 And when I say equals, it means the DNA is trying 428 00:20:14,700 --> 00:20:18,360 to tell the cell that this is the proper order 429 00:20:18,360 --> 00:20:21,033 in which the amino acid sequence should occur. 430 00:20:22,260 --> 00:20:26,430 It does this through a protein complex called ribosome. 431 00:20:26,430 --> 00:20:28,770 Ribosomes will actually bind directly 432 00:20:28,770 --> 00:20:30,913 to the mRNA in the cytoplasm 433 00:20:30,913 --> 00:20:34,470 and using other molecules, which we won't talk about 434 00:20:34,470 --> 00:20:37,500 in a lot of detail 'cause it starts to get pretty technical. 435 00:20:37,500 --> 00:20:40,500 But another molecule called tRNA 436 00:20:40,500 --> 00:20:45,453 or transfer RNA, which has three bases on it. 437 00:20:47,610 --> 00:20:50,430 Which when it binds, remember binding 438 00:20:50,430 --> 00:20:55,430 and base pairing from the DNA double strand? 439 00:20:55,500 --> 00:20:57,300 This is occurring here as well. 440 00:20:57,300 --> 00:20:59,430 But in very short segments, in segments 441 00:20:59,430 --> 00:21:03,210 of three bases at a time, three bases at a time. 442 00:21:03,210 --> 00:21:07,680 That's called that triplet of bases is called a codon. 443 00:21:07,680 --> 00:21:08,513 The reason why it's called a codon is 444 00:21:08,513 --> 00:21:12,870 'cause it codes for a specific amino acid. 445 00:21:12,870 --> 00:21:16,890 Three bases in a specific order will give the instructions 446 00:21:16,890 --> 00:21:18,960 for one specific amino acid. 447 00:21:18,960 --> 00:21:22,680 Three bases equals code for one amino acid. 448 00:21:22,680 --> 00:21:25,530 And the tRNA is really what is the missing link there. 449 00:21:25,530 --> 00:21:29,610 So it has three bases, which it's complimentary 450 00:21:29,610 --> 00:21:32,783 to a specific codon and it attaches itself 451 00:21:32,783 --> 00:21:35,610 to a specific amino acid. 452 00:21:35,610 --> 00:21:38,640 And that way it knows it can come in 453 00:21:38,640 --> 00:21:42,341 and the particular, say tRNA, which has attached 454 00:21:42,341 --> 00:21:47,341 to it, the amino acids say glycine will only bind 455 00:21:47,430 --> 00:21:50,100 to the triplet of nucleotide. 456 00:21:50,100 --> 00:21:54,993 So the three base sequence that corresponds to glycine. 457 00:21:56,430 --> 00:21:59,670 And the ribosome will actually kind of glide 458 00:21:59,670 --> 00:22:03,060 along the messenger, RNA from one end, 459 00:22:03,060 --> 00:22:05,485 specifically one end to the other end. 460 00:22:05,485 --> 00:22:07,320 And as it glides along, 461 00:22:07,320 --> 00:22:10,800 it will read each triplet three at a time. 462 00:22:10,800 --> 00:22:13,527 So it reads this three, for example. 463 00:22:13,527 --> 00:22:15,090 Then it would hop over 464 00:22:15,090 --> 00:22:18,660 and read the next three, read which amino acid 465 00:22:18,660 --> 00:22:21,120 that is using tRNA and then it would hop over 466 00:22:21,120 --> 00:22:23,310 and it'll read the next set of three. 467 00:22:23,310 --> 00:22:25,620 Find that right tRNA with the right amino acid. 468 00:22:25,620 --> 00:22:29,610 And all along these amino acids, the tRNA is being released, 469 00:22:29,610 --> 00:22:31,229 but the amino acid stays behind 470 00:22:31,229 --> 00:22:33,497 and it gets attached using the ribosome 471 00:22:33,497 --> 00:22:35,520 to the previous amino acid. 472 00:22:35,520 --> 00:22:38,550 So you're left with is a long chain of amino acids 473 00:22:38,550 --> 00:22:41,760 that all corresponded to the particular codon 474 00:22:41,760 --> 00:22:45,273 of the mRNA as as the ribosome has moved along it. 475 00:22:46,493 --> 00:22:48,583 This whole process is called translation 476 00:22:48,583 --> 00:22:50,403 or protein synthesis. 477 00:22:52,230 --> 00:22:54,480 Alright, take a second to soak that in (chuckles) 478 00:22:54,480 --> 00:22:57,750 and we're gonna talk about it in more detail now. 479 00:22:57,750 --> 00:22:59,670 Transcription. Let's go back to that. 480 00:22:59,670 --> 00:23:03,210 This is that first stage. Proteins called RNA polymerase. 481 00:23:03,210 --> 00:23:04,950 You don't really need to know the name of it, 482 00:23:04,950 --> 00:23:08,550 but I figure you should at least be exposed to it once. 483 00:23:08,550 --> 00:23:12,120 So proteins called RNA polymerase will bind to one strand 484 00:23:12,120 --> 00:23:14,610 of double stranded DNA within a gene. 485 00:23:14,610 --> 00:23:16,110 And the one strand that it binds 486 00:23:16,110 --> 00:23:18,450 to is called the antisense strand, 487 00:23:18,450 --> 00:23:21,068 and it will make a complimentary strand out 488 00:23:21,068 --> 00:23:24,918 of ribonucleic acid called mRNA. 489 00:23:24,918 --> 00:23:27,210 This is a similar structure 490 00:23:27,210 --> 00:23:29,760 to DNA except it's always single stranded. 491 00:23:29,760 --> 00:23:32,640 RNA is is really, there are some exceptions to 492 00:23:32,640 --> 00:23:33,990 that are important exceptions, 493 00:23:33,990 --> 00:23:37,020 but not for the context of this class. 494 00:23:37,020 --> 00:23:38,040 In the context of this class, 495 00:23:38,040 --> 00:23:40,137 you can just assume RNA is going to be single stranded, 496 00:23:40,137 --> 00:23:43,170 and mRNA really is single stranded. 497 00:23:43,170 --> 00:23:44,910 So it's similar, but instead 498 00:23:44,910 --> 00:23:49,020 of a deoxyribose sugar, it has just a ribose sugar 499 00:23:49,020 --> 00:23:53,250 that it's less likely to form a double stranded structure. 500 00:23:53,250 --> 00:23:56,132 The other difference is that instead, 501 00:23:56,132 --> 00:23:59,820 so while mRNA has very similar nucleotides 502 00:23:59,820 --> 00:24:03,480 to DNA, the bases are similar there. 503 00:24:03,480 --> 00:24:07,950 It has G, it has C, the only exception is T. 504 00:24:07,950 --> 00:24:12,950 So thymine instead of thymine mRNA uses uracil 505 00:24:13,530 --> 00:24:16,110 or the letter U you can replace there. 506 00:24:16,110 --> 00:24:18,210 So anytime you see a T 507 00:24:18,210 --> 00:24:19,752 in the DNA sequence, when you're thinking about 508 00:24:19,752 --> 00:24:23,550 what would the RNA sequence be for that? 509 00:24:23,550 --> 00:24:27,030 You can replace that T with a U. 510 00:24:27,030 --> 00:24:30,420 The reason why it needs to do that is because having uracil 511 00:24:30,420 --> 00:24:34,080 or U present in the sequence targets it 512 00:24:34,080 --> 00:24:37,470 for transport out of the nucleus, that's important. 513 00:24:37,470 --> 00:24:39,960 And it's important that DNA does not have U 514 00:24:39,960 --> 00:24:41,880 or uracil in its sequence 515 00:24:41,880 --> 00:24:45,090 because otherwise DNA would escape the nucleus 516 00:24:45,090 --> 00:24:46,740 and it would no longer be protected 517 00:24:46,740 --> 00:24:49,920 in its nice little environment in the nucleus. 518 00:24:49,920 --> 00:24:52,530 Instead, mRNA has uracil instead 519 00:24:52,530 --> 00:24:55,500 of thymine, which then allows it to escape the nucleus 520 00:24:55,500 --> 00:24:58,803 and get into the cytoplasm for translation. 521 00:25:00,360 --> 00:25:02,640 Okay, so I think we covered the rest of this. 522 00:25:02,640 --> 00:25:05,460 It's single stranded has only one strand and is short. 523 00:25:05,460 --> 00:25:06,293 Oh, right, it's short. 524 00:25:06,293 --> 00:25:09,420 So it's only the length of a single gene. 525 00:25:09,420 --> 00:25:12,870 And as you recall, a gene, a single gene takes up 526 00:25:12,870 --> 00:25:17,733 a very small stretch of the total length of a DNA strand. 527 00:25:19,050 --> 00:25:21,390 The mRNA sequence is complimentary 528 00:25:21,390 --> 00:25:24,000 to the antisense strand and identical 529 00:25:24,000 --> 00:25:27,540 to the sense strand, again, except U replacing T. 530 00:25:27,540 --> 00:25:30,210 So when we're talking about the being complimentary 531 00:25:30,210 --> 00:25:33,900 and identical, we'll look at that on the next slide. 532 00:25:33,900 --> 00:25:35,113 But just think of it this way 533 00:25:35,113 --> 00:25:37,830 and sometimes, let me just say, sometimes 534 00:25:37,830 --> 00:25:41,430 in genetics we use some strange terms like antisense 535 00:25:41,430 --> 00:25:45,810 and sense, there's usually some logic to it though, 536 00:25:45,810 --> 00:25:48,150 so when we say antisense strand, it binds 537 00:25:48,150 --> 00:25:50,250 and copies the antisense strand. 538 00:25:50,250 --> 00:25:52,350 So it's going to be complimentary to that, 539 00:25:52,350 --> 00:25:56,760 which means it's going to be identical to the other strand. 540 00:25:56,760 --> 00:25:57,900 If you're complimentary 541 00:25:57,900 --> 00:26:00,000 to the complimentary strand, (chuckles) it's going 542 00:26:00,000 --> 00:26:02,220 to be the same as that original strand. 543 00:26:02,220 --> 00:26:04,260 It'll sink in a second. 544 00:26:04,260 --> 00:26:06,270 I wanna show you the next slide hopefully, 545 00:26:06,270 --> 00:26:07,620 but just think of it that way. 546 00:26:07,620 --> 00:26:11,010 So mRNA sequence is complimentary 547 00:26:11,010 --> 00:26:14,253 to the antisense strand and identical to the sense strand. 548 00:26:15,840 --> 00:26:19,110 Let's look at an example of what the heck I'm talking about. 549 00:26:19,110 --> 00:26:22,680 Okay, again, let's say this is your gene here, 550 00:26:22,680 --> 00:26:27,540 again, most virtually all genes I can confidently say 551 00:26:27,540 --> 00:26:29,640 all genes are gonna be longer than this, 552 00:26:29,640 --> 00:26:32,070 but it's just to give you a sense of scale. 553 00:26:32,070 --> 00:26:33,600 Let's say this is your DNA strand. 554 00:26:33,600 --> 00:26:37,290 Remember, DNA in the nucleus is normally compacted 555 00:26:37,290 --> 00:26:38,985 into chromosomes. 556 00:26:38,985 --> 00:26:41,250 So we're just stretching it out here 557 00:26:41,250 --> 00:26:43,620 so you can kind of see what's going on. 558 00:26:43,620 --> 00:26:45,450 If we stretch out, you can see 559 00:26:45,450 --> 00:26:48,390 that the two strands, which are normally bonded together 560 00:26:48,390 --> 00:26:53,390 right through base pairing are separated slightly here so 561 00:26:53,668 --> 00:26:57,150 that the two strands are separate from one another. 562 00:26:57,150 --> 00:27:02,150 And RNA can start to form a complementary strand 563 00:27:02,340 --> 00:27:07,340 to the antisense strand using RNA polymerase, 564 00:27:07,350 --> 00:27:10,260 which is this blob here that's coming along 565 00:27:10,260 --> 00:27:12,990 and it goes in a specific direction. 566 00:27:12,990 --> 00:27:15,930 In this instance, it's going from left to right. 567 00:27:15,930 --> 00:27:18,358 So it's going from this side to this side. 568 00:27:18,358 --> 00:27:20,460 The RNA polymerase is moving along 569 00:27:20,460 --> 00:27:22,620 and as it hits particular base, 570 00:27:22,620 --> 00:27:24,758 so let's say it's hitting this particular 571 00:27:24,758 --> 00:27:28,050 guanine here in the antisense strand, it's going to read 572 00:27:28,050 --> 00:27:30,390 that and it's going to know, okay, we need a cytosine. 573 00:27:30,390 --> 00:27:33,240 'cause cytosines going to be complimentary to guanine, 574 00:27:33,240 --> 00:27:35,100 remember C binds to G. 575 00:27:35,100 --> 00:27:37,002 So it will put down a C here. 576 00:27:37,002 --> 00:27:42,002 When it reaches this adenine, this A here. 577 00:27:42,270 --> 00:27:46,110 Remember, the complimentary base 578 00:27:46,110 --> 00:27:48,570 in DNA would be thymine or T. 579 00:27:48,570 --> 00:27:50,580 But since we're talking about RNA, 580 00:27:50,580 --> 00:27:53,190 what replaces thymine in RNA? 581 00:27:53,190 --> 00:27:55,710 That's right, it's uracil or U. 582 00:27:55,710 --> 00:27:59,760 So instead of putting down the base T here, 583 00:27:59,760 --> 00:28:01,080 which you would see is present 584 00:28:01,080 --> 00:28:03,423 in the sense strand, it would use a U. 585 00:28:04,650 --> 00:28:06,840 So the next bases, 586 00:28:06,840 --> 00:28:09,510 you can always predict what it's going to put down. 587 00:28:09,510 --> 00:28:13,307 If this is a C here, it would go GCC UUA ACC GC. 588 00:28:24,216 --> 00:28:25,350 Do you get what I'm saying here? 589 00:28:25,350 --> 00:28:27,900 It's complimentary to the strand. 590 00:28:27,900 --> 00:28:29,130 And you can start 591 00:28:29,130 --> 00:28:31,110 to see why this is called the sense strand. 592 00:28:31,110 --> 00:28:32,550 While there's no, there's nothing going 593 00:28:32,550 --> 00:28:34,080 on here, there's no activity going on 594 00:28:34,080 --> 00:28:36,600 on this strand, it's not being copied. 595 00:28:36,600 --> 00:28:39,270 But what is happening, the sequence identical 596 00:28:39,270 --> 00:28:43,320 to it is being created because the sequence complementary 597 00:28:43,320 --> 00:28:45,450 to the antisense strand is what's being made. 598 00:28:45,450 --> 00:28:49,503 So it moves along until it reaches the end of the gene. 599 00:28:50,760 --> 00:28:53,880 And this is where the mRNA will fall off. 600 00:28:53,880 --> 00:28:56,580 The single stranded mRNA will fall off of the DNA. 601 00:28:56,580 --> 00:28:58,770 The DNA will bind back together. 602 00:28:58,770 --> 00:29:00,570 So the two strands will come back together 603 00:29:00,570 --> 00:29:02,820 and will fold itself right back up 604 00:29:02,820 --> 00:29:06,030 into, its tightly wound chromosome formation 605 00:29:06,030 --> 00:29:09,063 and the mRNA will leave the nucleus. 606 00:29:10,680 --> 00:29:12,960 Let's move on to translation. 607 00:29:12,960 --> 00:29:17,340 mRNA exits the nucleus and reaches ribosomes, ribosomes bind 608 00:29:17,340 --> 00:29:20,880 to mRNA and facilitate protein synthesis using complementary 609 00:29:20,880 --> 00:29:24,510 molecules called tRNA, which bring a specific amino acid 610 00:29:24,510 --> 00:29:27,360 to match a specific mRNA codon sequence. 611 00:29:27,360 --> 00:29:32,360 Remember, codons are sets of three bases along the mRNA. 612 00:29:34,170 --> 00:29:36,959 The tRNA as I mentioned before, it's kind 613 00:29:36,959 --> 00:29:38,970 of the missing link, the bridge 614 00:29:38,970 --> 00:29:43,350 between nucleic acid and amino acid. 615 00:29:43,350 --> 00:29:45,780 So it has an amino acid attached to it, 616 00:29:45,780 --> 00:29:50,780 but it also has a sequence a codon which will bind 617 00:29:51,540 --> 00:29:55,060 to a specific codon and will deposit its amino acid 618 00:29:55,060 --> 00:29:57,900 into the growing protein chain 619 00:29:57,900 --> 00:30:01,257 that is housed on the ribosome. 620 00:30:01,257 --> 00:30:02,490 The ribosome will move 621 00:30:02,490 --> 00:30:04,740 in a specific direction along the mRNA 622 00:30:04,740 --> 00:30:08,583 and will basically shoot out the protein as it goes along. 623 00:30:10,200 --> 00:30:13,500 The ribosome will continue to move along the full length 624 00:30:13,500 --> 00:30:16,500 of the mRNA molecule until it reaches a specific codon. 625 00:30:16,500 --> 00:30:20,640 So remember, codon is a triplet of bases. 626 00:30:20,640 --> 00:30:24,480 So until it reaches a specific sequence called a stop codon, 627 00:30:24,480 --> 00:30:27,840 where it's told to essentially fall off and it does, 628 00:30:27,840 --> 00:30:30,900 and the protein has been completed. 629 00:30:30,900 --> 00:30:31,950 Breaking the code. 630 00:30:31,950 --> 00:30:35,940 So this really is like the code breakers of World War II. 631 00:30:35,940 --> 00:30:38,610 This is kind of the same approach that had to be taken 632 00:30:38,610 --> 00:30:40,950 to figure this code out. 633 00:30:40,950 --> 00:30:43,650 And it has been, and it is very consistent. 634 00:30:43,650 --> 00:30:44,490 We're not talking just 635 00:30:44,490 --> 00:30:49,170 in humans, we're talking about all living species 636 00:30:49,170 --> 00:30:54,170 is just astounding to me how highly conserved this is 637 00:30:54,180 --> 00:30:56,970 across literally every living species 638 00:30:56,970 --> 00:31:00,030 that's been explored has the same code. 639 00:31:00,030 --> 00:31:01,440 How cool is that? 640 00:31:01,440 --> 00:31:04,740 That, I mean, just billions of years of life in evolution. 641 00:31:04,740 --> 00:31:07,923 It has continued to remain identical throughout that. 642 00:31:09,300 --> 00:31:12,000 The base sequence of a gene contains coded information 643 00:31:12,000 --> 00:31:14,160 for ribosomes to make proteins properly, 644 00:31:14,160 --> 00:31:16,047 which is what we've been talking about here. 645 00:31:16,047 --> 00:31:19,350 And the bases are read from mRNA sequentially 646 00:31:19,350 --> 00:31:21,960 in groups of three called codons. 647 00:31:21,960 --> 00:31:24,930 So from just giving you an example of a stretch 648 00:31:24,930 --> 00:31:27,810 of mRNA sequence from reused, replaced Ts 649 00:31:27,810 --> 00:31:31,805 from the DNA sequence, we would read the codons 650 00:31:31,805 --> 00:31:36,805 as follows, AUG/CGU/GGU/AAC/GUA. 651 00:31:38,910 --> 00:31:41,220 So it goes in sets of three, it reads this set 652 00:31:41,220 --> 00:31:43,710 and it moves to the next set of three, and then it moves 653 00:31:43,710 --> 00:31:46,053 to the next set of three and so on and so on. 654 00:31:47,260 --> 00:31:50,370 AUG is universally recognized by ribosomes 655 00:31:50,370 --> 00:31:52,260 as a signal to start translation. 656 00:31:52,260 --> 00:31:55,350 So all proteins start with methionine 657 00:31:55,350 --> 00:31:59,730 because the tRNA, which recognizes AUG, carries 658 00:31:59,730 --> 00:32:02,403 with it the amino acid methionine. 659 00:32:03,270 --> 00:32:04,170 Each codon codes 660 00:32:04,170 --> 00:32:06,990 for specific amino acid except the three codons, 661 00:32:06,990 --> 00:32:09,190 which tell the ribosome to stop translating. 662 00:32:11,010 --> 00:32:12,870 That doesn't have a corresponding tRNA. 663 00:32:12,870 --> 00:32:15,000 And as a result, the ribosome just kinda gets stuck there. 664 00:32:15,000 --> 00:32:16,800 It's like, oh, okay, I guess we're done. 665 00:32:16,800 --> 00:32:18,450 And it sort of falls off. 666 00:32:18,450 --> 00:32:21,660 And then the protein, the chain of amino acids, 667 00:32:21,660 --> 00:32:24,210 which is the protein can go along its way 668 00:32:24,210 --> 00:32:28,773 and form its structure and do its function. 669 00:32:30,704 --> 00:32:35,704 The three stop codons are UGA, UAA and UAG. 670 00:32:36,300 --> 00:32:37,800 Given that there are four bases, 671 00:32:37,800 --> 00:32:42,800 so A, U, C and G four bases in RNA and three positions 672 00:32:45,360 --> 00:32:48,900 for a base per codon, because a codon is a triplet 673 00:32:48,900 --> 00:32:52,320 or three bases, there are 64 possible different codons. 674 00:32:52,320 --> 00:32:54,000 So four to the third power, 675 00:32:54,000 --> 00:32:56,130 but there are only 20 different amino acids. 676 00:32:56,130 --> 00:32:58,410 So most amino acids actually are coded 677 00:32:58,410 --> 00:33:01,530 for by multiple codons. 678 00:33:01,530 --> 00:33:05,700 So it's not just a single three base sequence 679 00:33:05,700 --> 00:33:09,210 that codes for a single amino acid. 680 00:33:09,210 --> 00:33:12,780 One amino acid can have multiple different codons 681 00:33:12,780 --> 00:33:13,713 that code for it. 682 00:33:15,570 --> 00:33:17,970 This can be a good friend for you 683 00:33:17,970 --> 00:33:21,030 if you're ever doing any work where you need 684 00:33:21,030 --> 00:33:23,730 to decode a specific sequence 685 00:33:23,730 --> 00:33:28,620 to understand what the sequence is coding for. 686 00:33:28,620 --> 00:33:30,930 So which amino acids it's coding for. 687 00:33:30,930 --> 00:33:32,430 This is called a codon table. 688 00:33:32,430 --> 00:33:33,990 And you can find it, you can Google it. 689 00:33:33,990 --> 00:33:36,690 It'll come up, I think there's one in the textbook. 690 00:33:36,690 --> 00:33:40,890 There's one in the excerpts from the textbook 691 00:33:40,890 --> 00:33:42,570 that I included as well. 692 00:33:42,570 --> 00:33:43,403 They're everywhere. 693 00:33:43,403 --> 00:33:46,290 So just look for codon table, you'll find this. 694 00:33:46,290 --> 00:33:48,480 The way you read this is, remember 695 00:33:48,480 --> 00:33:49,770 there are three bases, right? 696 00:33:49,770 --> 00:33:51,060 Three bases in a codon. 697 00:33:51,060 --> 00:33:55,320 You have the first base along the left hand side here. 698 00:33:55,320 --> 00:33:59,100 So vertically along the left hand side, you find, which 699 00:33:59,100 --> 00:34:00,090 is your first base. 700 00:34:00,090 --> 00:34:02,910 So let's say it's a C. Okay, there's C. 701 00:34:02,910 --> 00:34:04,530 Then you need to know what's your second base. 702 00:34:04,530 --> 00:34:07,917 Let's say your second base is an A, okay, well you look here 703 00:34:07,917 --> 00:34:12,120 and then your third base, let's say is, 704 00:34:12,120 --> 00:34:15,330 so we had C, A let's say your third base is a G. 705 00:34:15,330 --> 00:34:19,843 So we would look under C, come over to A, G. 706 00:34:21,342 --> 00:34:24,690 It says CAG, here it is. What is that code for? 707 00:34:24,690 --> 00:34:27,120 Codes for glutamine. 708 00:34:27,120 --> 00:34:28,650 This is giving you the letters are 709 00:34:28,650 --> 00:34:31,950 the single letter designations for each of the amino acids. 710 00:34:31,950 --> 00:34:35,640 Which is sort of a standard designation for each of them. 711 00:34:35,640 --> 00:34:38,400 So you can look at it this way, you know, you can figure it 712 00:34:38,400 --> 00:34:40,200 out that way you can also just kind of glance 713 00:34:40,200 --> 00:34:41,280 through the chart if you don't want 714 00:34:41,280 --> 00:34:43,080 to use the different columns. 715 00:34:43,080 --> 00:34:44,700 Let's say, you know, you're looking 716 00:34:44,700 --> 00:34:49,700 for what is AAG, oh, well here's AAG that codes for lysine. 717 00:34:50,580 --> 00:34:52,020 Got it. Okay. 718 00:34:52,020 --> 00:34:55,660 So this is a very handy useful table 719 00:34:57,850 --> 00:35:02,520 that you can use in decoding DNA sequence. 720 00:35:02,520 --> 00:35:04,110 So here are a few tricks 721 00:35:04,110 --> 00:35:06,450 for quickly decoding a DNA sequence. 722 00:35:06,450 --> 00:35:08,220 So if this is the DNA sequence. 723 00:35:08,220 --> 00:35:10,860 Let's say this is these are the two complimentary strands 724 00:35:10,860 --> 00:35:14,310 to one another, you can tell, first of all, this is DNA. 725 00:35:14,310 --> 00:35:18,030 Why? Because there's thymine here and it's not uracil. 726 00:35:18,030 --> 00:35:20,880 So we know it's DNA. No, it's not RNA. 727 00:35:20,880 --> 00:35:22,290 So this is DNA, 728 00:35:22,290 --> 00:35:25,080 and we know these two are complimentary to one another. 729 00:35:25,080 --> 00:35:27,390 How do we know that? Well, because they are. 730 00:35:27,390 --> 00:35:31,290 So A is complimentary to T. T to A, G to C, C to. 731 00:35:31,290 --> 00:35:33,300 So we know these two strands are complimentary 732 00:35:33,300 --> 00:35:34,203 to one another. 733 00:35:36,000 --> 00:35:37,980 If we're looking at this DNA sequence 734 00:35:37,980 --> 00:35:42,280 and we want to know what is the sequence 735 00:35:43,200 --> 00:35:45,600 of amino acids that this is coding for? 736 00:35:45,600 --> 00:35:47,340 What we can do very quickly is think 737 00:35:47,340 --> 00:35:52,170 of, okay, well what would the RNA sequence be for this? 738 00:35:52,170 --> 00:35:54,570 All you have to do is change the antisense strand. 739 00:35:54,570 --> 00:35:59,570 T, anytime there's a T to a U and separating the codons. 740 00:35:59,850 --> 00:36:01,237 What do I mean by that? 741 00:36:01,237 --> 00:36:04,110 So the first codon, the first three triplet 742 00:36:04,110 --> 00:36:06,750 of bases is ATG. 743 00:36:06,750 --> 00:36:10,140 We change that to AUG because instead of Ts we have Us 744 00:36:10,140 --> 00:36:15,140 in RNA sequence, then the next set would be CGG. 745 00:36:15,630 --> 00:36:17,850 Well, nothing to change there. It's just CGG. 746 00:36:17,850 --> 00:36:22,850 The next set is TAC, oh, there's T, it becomes U, UAC. 747 00:36:23,192 --> 00:36:26,343 And the next set is GTA, which oh, that becomes GUA. 748 00:36:27,330 --> 00:36:31,083 And then the last set here is TGA, which becomes UGA. 749 00:36:32,841 --> 00:36:36,480 And you just go back to your handy dandy codon table 750 00:36:36,480 --> 00:36:38,010 and you look each one of those up 751 00:36:38,010 --> 00:36:40,153 and you say, okay, well the first one is AUG. 752 00:36:40,153 --> 00:36:41,190 It's always going to be the first one. 753 00:36:41,190 --> 00:36:43,673 If you're starting from the beginning of the protein. 754 00:36:44,609 --> 00:36:48,990 AUG, whoop, there it is. Methionine, that's the start codon. 755 00:36:48,990 --> 00:36:53,040 Okay, so we have methionine, methionine here. 756 00:36:53,040 --> 00:36:55,920 Then the next one is CGG. Let's go back to that table. 757 00:36:55,920 --> 00:37:00,503 CGG, like the sound effects? (chuckles) 758 00:37:02,717 --> 00:37:07,020 All right, so CGG is arginine. Let's go back. 759 00:37:07,020 --> 00:37:11,250 Hey arginine, so we write an arginine. The next one is UAC. 760 00:37:11,250 --> 00:37:16,250 Let's cut back here UAC, that's tyrosine, Tyrosine. 761 00:37:19,260 --> 00:37:22,083 Then you know the next one is GUA. G, U, A. 762 00:37:25,260 --> 00:37:28,797 That's valine. Yep, valine. 763 00:37:28,797 --> 00:37:33,797 And the last one is UGA. U, G, A. 764 00:37:34,170 --> 00:37:36,014 Oh, there's no amino acid here. 765 00:37:36,014 --> 00:37:39,300 Well that's very true because it is a stop codon. 766 00:37:39,300 --> 00:37:41,370 Remember, stop codon does not actually code 767 00:37:41,370 --> 00:37:42,203 for an amino acid. 768 00:37:42,203 --> 00:37:44,640 It simply tells the ribosome, okay, we're done here. 769 00:37:44,640 --> 00:37:48,900 We stop. We've made the protein and that's what it is. 770 00:37:48,900 --> 00:37:50,127 So your amino acid sequence would read 771 00:37:50,127 --> 00:37:53,793 Methionine, Arginine, Tyrosine, Valine. 772 00:37:54,630 --> 00:37:59,630 That's it. All right, let's summarize what we have so far. 773 00:37:59,775 --> 00:38:02,760 DNA instructs the proper formation of all proteins 774 00:38:02,760 --> 00:38:04,590 without ever leaving the nucleus. 775 00:38:04,590 --> 00:38:06,360 Pretty neat trick, I'd have to say. 776 00:38:06,360 --> 00:38:09,060 Central dogma reads DNA to RNA 777 00:38:09,060 --> 00:38:10,830 to protein, always in that order. 778 00:38:10,830 --> 00:38:14,490 Always, always, always. Transcription is the first stage. 779 00:38:14,490 --> 00:38:17,580 The antisense strand of DNA for a particular gene is copied 780 00:38:17,580 --> 00:38:20,026 into complementary mRNA in the nucleus. 781 00:38:20,026 --> 00:38:23,220 Then that mRNA exits the nucleus 782 00:38:23,220 --> 00:38:24,487 and we start in translation 783 00:38:24,487 --> 00:38:28,243 in which the mRNA reaches ribosomes, which bind 784 00:38:28,243 --> 00:38:31,110 to it and facilitate assembly of amino acids 785 00:38:31,110 --> 00:38:33,180 in the order dictated by the sequence. 786 00:38:33,180 --> 00:38:35,220 Remember, transcription happens 787 00:38:35,220 --> 00:38:37,026 in the nucleus, translation happens 788 00:38:37,026 --> 00:38:39,684 in the cytoplasm or outside of the nucleus. 789 00:38:39,684 --> 00:38:42,180 Ribosomes read mRNA a sequence in sets 790 00:38:42,180 --> 00:38:45,180 of three adjacent bases called codons, starting 791 00:38:45,180 --> 00:38:47,970 with AUG and ending with one 792 00:38:47,970 --> 00:38:52,593 of three different stop codons, UGA, UAA or UAG. 793 00:38:53,520 --> 00:38:55,320 Each codon codes specifically 794 00:38:55,320 --> 00:38:58,980 for 1 of 20 amino acids or a stop codon. 795 00:38:58,980 --> 00:39:02,613 And each amino acid may have multiple codon sequences. 796 00:39:04,140 --> 00:39:08,100 All right, well what's in the next module? 797 00:39:08,100 --> 00:39:10,440 You're asking you ready to go? You ready for more? 798 00:39:10,440 --> 00:39:12,183 I hope so. I really do. 799 00:39:13,020 --> 00:39:16,140 Just know that again, once you get these basics down, 800 00:39:16,140 --> 00:39:19,380 we can start really talking about the applications of this. 801 00:39:19,380 --> 00:39:20,640 And remember, you're going 802 00:39:20,640 --> 00:39:22,620 to have this reinforced again and again and again. 803 00:39:22,620 --> 00:39:24,930 So if you don't 100% get it yet 804 00:39:24,930 --> 00:39:27,324 and not totally comfortable with it, it's okay. 805 00:39:27,324 --> 00:39:31,020 You'll get there. I know you will absolutely get there. 806 00:39:31,020 --> 00:39:32,250 So what's in the next module? 807 00:39:32,250 --> 00:39:34,590 We're going to talk about gene expression 808 00:39:34,590 --> 00:39:36,330 and what that means and as far 809 00:39:36,330 --> 00:39:41,330 as turning genes up down on off DNA replication. 810 00:39:41,700 --> 00:39:44,010 So how does the DNA 811 00:39:44,010 --> 00:39:48,240 in a single fertilized egg end up becoming the DNA 812 00:39:48,240 --> 00:39:51,360 in 50 trillion cells for an adult individual? 813 00:39:51,360 --> 00:39:53,160 How does the DNA replicate itself? 814 00:39:53,160 --> 00:39:56,370 And as part of that, we'll talk about mitosis and meiosis 815 00:39:56,370 --> 00:39:58,623 or the two processes of cell division. 816 00:39:59,970 --> 00:40:03,090 All right, with that, I want to direct you 817 00:40:03,090 --> 00:40:05,220 to a couple of different online resources. 818 00:40:05,220 --> 00:40:08,130 If you're curious about either learning more, seeing it 819 00:40:08,130 --> 00:40:10,740 in a different format, hearing it from someone else other 820 00:40:10,740 --> 00:40:13,260 than me, please, please use any sources 821 00:40:13,260 --> 00:40:14,492 that will be helpful to you. 822 00:40:14,492 --> 00:40:17,370 I'm going to post these on Blackboard site 823 00:40:17,370 --> 00:40:18,750 for you to click through too. 824 00:40:18,750 --> 00:40:20,370 But there's the Genetics Home reference, 825 00:40:20,370 --> 00:40:23,160 which is a great one to click through. 826 00:40:23,160 --> 00:40:26,580 University of Utah Genetic Science Learning Center is 827 00:40:26,580 --> 00:40:27,480 also wonderful. 828 00:40:27,480 --> 00:40:31,890 They have some great videos and some different animations 829 00:40:31,890 --> 00:40:33,360 that might help you to start 830 00:40:33,360 --> 00:40:36,003 to conceptualize what we've been talking about. 831 00:40:36,840 --> 00:40:38,891 And the National Institutes of Health 832 00:40:38,891 --> 00:40:43,890 and Gene Education Center that can also be quite helpful 833 00:40:43,890 --> 00:40:47,190 in just getting a different perspective on the same topics 834 00:40:47,190 --> 00:40:48,750 that we're discussing here. 835 00:40:48,750 --> 00:40:51,660 So with that, I'd like to thank you so much 836 00:40:51,660 --> 00:40:54,600 for your attention and for bearing with me through this. 837 00:40:54,600 --> 00:40:56,624 We will absolutely reach the point 838 00:40:56,624 --> 00:40:59,610 of talking about clinical applications 839 00:40:59,610 --> 00:41:03,540 that is not far away, but hopefully you're starting 840 00:41:03,540 --> 00:41:05,126 to feel a little bit more comfortable 841 00:41:05,126 --> 00:41:10,126 with the terminology, with the concepts of genetics. 842 00:41:10,410 --> 00:41:15,360 You will be amazed, I think, in how much better 843 00:41:15,360 --> 00:41:16,560 and easier it is to start 844 00:41:16,560 --> 00:41:18,230 to understand the clinical applications 845 00:41:18,230 --> 00:41:21,213 of this if you understand the basic science behind it. 846 00:41:22,320 --> 00:41:24,750 All right with that, I will sign off. 847 00:41:24,750 --> 00:41:27,660 So as always, please let me know if you have questions 848 00:41:27,660 --> 00:41:31,410 along the way and I'm more than happy to help 849 00:41:31,410 --> 00:41:34,233 with anything, provide additional resources where I can. 850 00:41:35,610 --> 00:41:39,423 And I will talk with you in the next module. Thank you.