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These are the user uploaded subtitles that are being translated: 0 00:00:00,000 --> 00:00:01,660 MICHAEL HEMANN: We have a pretty diverse group of people. 1 00:00:01,660 --> 00:00:03,870 So we're just going to start with a little bit 2 00:00:03,870 --> 00:00:07,530 of a refresher on some basics before we 3 00:00:07,530 --> 00:00:12,430 get into the genetics in subsequent lectures. 4 00:00:12,430 --> 00:00:20,190 So essentially the central dogma of biology 5 00:00:20,190 --> 00:00:31,550 is that we have DNA that goes to RNA that goes to protein. 6 00:00:31,550 --> 00:00:36,600 This is just the basic tenets of modern molecular biology. 7 00:00:36,600 --> 00:00:49,240 So DNA is copied in a process called DNA replication. 8 00:00:49,240 --> 00:00:52,960 DNA replication is essentially the polymerization 9 00:00:52,960 --> 00:00:56,880 of new DNA molecules templated by existing molecules. 10 00:00:56,880 --> 00:01:00,860 So if we just look at a short stretch of DNA here, 11 00:01:00,860 --> 00:01:05,260 a four-base sequence, We have a 5 prime phosphate, 12 00:01:05,260 --> 00:01:09,500 we have a 3 prime hydroxyl, we have two copies of this DNA. 13 00:01:09,500 --> 00:01:12,625 So we have the complementary strand here. 14 00:01:12,625 --> 00:01:17,380 15 00:01:17,380 --> 00:01:24,460 And this is replicated into two daughter molecules of DNA 16 00:01:24,460 --> 00:01:28,190 based on a process called semi-conservative replication, 17 00:01:28,190 --> 00:01:30,280 which means that each of these strands 18 00:01:30,280 --> 00:01:33,850 actually templates the addition of nucleotides 19 00:01:33,850 --> 00:01:35,840 to the other strand. 20 00:01:35,840 --> 00:01:47,170 So we have these two molecules that come apart, 21 00:01:47,170 --> 00:01:56,360 and you have the synthesis of new strands 22 00:01:56,360 --> 00:02:05,700 from 5 prime to 3 prime in both of the daughter strands. 23 00:02:05,700 --> 00:02:08,130 So from the big-picture perspective, 24 00:02:08,130 --> 00:02:10,995 we have a long sequence of DNA. 25 00:02:10,995 --> 00:02:21,440 26 00:02:21,440 --> 00:02:29,050 And we have the synthesis from 5 prime to 3 prime 27 00:02:29,050 --> 00:02:29,980 on both strands. 28 00:02:29,980 --> 00:02:33,310 One strand, you basically have continual synthesis 29 00:02:33,310 --> 00:02:34,980 from lots of origins or replication, 30 00:02:34,980 --> 00:02:38,060 and the other you have Okazaki fragments. 31 00:02:38,060 --> 00:02:41,740 So again, a semi-conservative strategy 32 00:02:41,740 --> 00:02:48,542 that leads to the production of two progeny molecules of DNA, 33 00:02:48,542 --> 00:02:50,500 half of which are the old DNA and half of which 34 00:02:50,500 --> 00:02:53,158 are newly synthesized from nucleotides that 35 00:02:53,158 --> 00:02:54,325 are sort of swimming around. 36 00:02:54,325 --> 00:02:57,510 37 00:02:57,510 --> 00:03:06,520 So the second process is this process of DNA to RNA. 38 00:03:06,520 --> 00:03:15,165 So transcription occurs off of a DNA template. 39 00:03:15,165 --> 00:03:19,758 40 00:03:19,758 --> 00:03:24,520 where we have the binding of an RNA polymerase 41 00:03:24,520 --> 00:03:28,460 to a transcriptional start site, and you 42 00:03:28,460 --> 00:03:36,250 have the new synthesis of an RNA that is essentially 43 00:03:36,250 --> 00:03:38,020 a copy of this top strand-- 44 00:03:38,020 --> 00:03:44,260 this synth strand-- from a migrating transcriptional 45 00:03:44,260 --> 00:03:44,760 bubble. 46 00:03:44,760 --> 00:03:51,250 So this is early in transcription, and this is late 47 00:03:51,250 --> 00:03:53,040 in transcription. 48 00:03:53,040 --> 00:03:58,650 where we have the production of a long RNA molecule that, 49 00:03:58,650 --> 00:04:03,120 again, is templated off this lower strand. 50 00:04:03,120 --> 00:04:05,680 It's identical to the top strand, of course. 51 00:04:05,680 --> 00:04:07,830 It's RNA and not DNA. 52 00:04:07,830 --> 00:04:09,810 So it's a different molecule-- 53 00:04:09,810 --> 00:04:13,500 less stable molecule-- that essentially is 54 00:04:13,500 --> 00:04:16,660 the active copy of our genome. 55 00:04:16,660 --> 00:04:19,140 So it's actively producing information 56 00:04:19,140 --> 00:04:21,539 that's used to encode proteins. 57 00:04:21,539 --> 00:04:24,290 58 00:04:24,290 --> 00:04:27,770 And so that synthesis of proteins-- 59 00:04:27,770 --> 00:04:39,570 so going from RNA to protein is called translation. 60 00:04:39,570 --> 00:04:42,500 So not all RNAs are translated. 61 00:04:42,500 --> 00:04:45,050 So you have lots of classes of RNAs 62 00:04:45,050 --> 00:04:49,160 like tRNAs and ribosomal RNAs that aren't translated. 63 00:04:49,160 --> 00:04:54,530 You have small RNAs that serve to regulate transcription, 64 00:04:54,530 --> 00:04:56,390 like microRNAs. 65 00:04:56,390 --> 00:05:01,190 But all proteins are encoded through the translation 66 00:05:01,190 --> 00:05:03,080 of mRNAs. 67 00:05:03,080 --> 00:05:08,380 And so you have a ribosome, you have an mRNA, 68 00:05:08,380 --> 00:05:14,640 and then you have addition of amino acids 69 00:05:14,640 --> 00:05:20,080 to a growing polypeptide through the introduction 70 00:05:20,080 --> 00:05:26,520 of tRNA-loaded individual amino acids. 71 00:05:26,520 --> 00:05:31,590 So the step wide addition of amino acids 72 00:05:31,590 --> 00:05:33,930 to a polypeptide chain leads to the production 73 00:05:33,930 --> 00:05:35,490 of a large polypeptide. 74 00:05:35,490 --> 00:05:41,760 This large polypeptide is folded into a diverse class 75 00:05:41,760 --> 00:05:43,320 of proteins in the cell-- 76 00:05:43,320 --> 00:05:46,590 proteins including enzymes and receptors 77 00:05:46,590 --> 00:05:49,890 and structural proteins and hormones and lots 78 00:05:49,890 --> 00:05:51,810 of different classes of proteins, 79 00:05:51,810 --> 00:05:54,910 essentially, all made during this process. 80 00:05:54,910 --> 00:06:00,900 And so again, the central dogma of molecular biology 81 00:06:00,900 --> 00:06:04,800 and genetics is that you have a gene which 82 00:06:04,800 --> 00:06:13,270 is a double stranded piece of DNA that yields an RNA that 83 00:06:13,270 --> 00:06:19,810 is a smaller sequence from a transcriptional start site down 84 00:06:19,810 --> 00:06:21,970 to a polyadenylation site. 85 00:06:21,970 --> 00:06:28,480 And this encodes for the translation of a protein 86 00:06:28,480 --> 00:06:32,710 from the start codon like AUG-- 87 00:06:32,710 --> 00:06:36,160 and there are some degenerate start codons-- 88 00:06:36,160 --> 00:06:38,620 but mostly AUG. 89 00:06:38,620 --> 00:06:40,390 So this is the basic principle. 90 00:06:40,390 --> 00:06:44,965 This is the gene as a structural entity. 91 00:06:44,965 --> 00:06:50,370 92 00:06:50,370 --> 00:06:54,780 So a typical gene in our cells-- 93 00:06:54,780 --> 00:07:00,500 average gene is around one to two kilobases, 94 00:07:00,500 --> 00:07:02,660 so 1,000 to 2,000 bases. 95 00:07:02,660 --> 00:07:08,870 That corresponds with a triplet code to 300 to 600, 96 00:07:08,870 --> 00:07:13,850 or 333 to 666 amino acids. 97 00:07:13,850 --> 00:07:16,650 There are genes that are much larger. 98 00:07:16,650 --> 00:07:23,250 So dystrophin, for example, is a gene 99 00:07:23,250 --> 00:07:26,550 that is two million base pairs. 100 00:07:26,550 --> 00:07:29,850 This is the gene that is altered in the condition Duchenne's 101 00:07:29,850 --> 00:07:31,780 muscular dystrophy. 102 00:07:31,780 --> 00:07:34,020 It's mostly introns, which we'll talk about. 103 00:07:34,020 --> 00:07:38,880 But in total physical length, it is two million bases. 104 00:07:38,880 --> 00:07:40,320 Genes can be very small. 105 00:07:40,320 --> 00:07:42,930 They can be 30 or 40 amino acids. 106 00:07:42,930 --> 00:07:46,530 And sometimes it's actually very difficult actually to predict 107 00:07:46,530 --> 00:07:49,060 whether something is a protein-coding gene or not-- 108 00:07:49,060 --> 00:07:50,350 and we'll talk about that-- 109 00:07:50,350 --> 00:07:53,070 how do we know what a gene is, how do we assess 110 00:07:53,070 --> 00:07:54,600 whether it's protein coding. 111 00:07:54,600 --> 00:07:56,400 When we say that we actually have 112 00:07:56,400 --> 00:07:58,420 a certain number of genes in the genome, 113 00:07:58,420 --> 00:08:00,120 how and why are we saying that? 114 00:08:00,120 --> 00:08:01,680 How can we possibly predict that? 115 00:08:01,680 --> 00:08:07,010 116 00:08:07,010 --> 00:08:14,060 E. coli has around 4,000 genes. 117 00:08:14,060 --> 00:08:19,380 We are at the other end of the spectrum. 118 00:08:19,380 --> 00:08:28,870 So humans have 20,000 to 25,000 genes. 119 00:08:28,870 --> 00:08:31,090 Actually, this number has evolved over time. 120 00:08:31,090 --> 00:08:33,765 Initially, but prior to the human genome sequence, 121 00:08:33,765 --> 00:08:35,890 it was thought that there were about 100,000 genes, 122 00:08:35,890 --> 00:08:37,630 but we're simpler than we thought. 123 00:08:37,630 --> 00:08:39,909 But there are much more simple organisms. 124 00:08:39,909 --> 00:08:51,070 For example, an organism with the perhaps unfortunate name 125 00:08:51,070 --> 00:08:56,140 Mycoplasma genitalium has the fewest genes of any organism. 126 00:08:56,140 --> 00:09:00,370 It's 467 genes, so that's basically the bare bones. 127 00:09:00,370 --> 00:09:04,750 That's what you need to get by in the world, around 467 genes. 128 00:09:04,750 --> 00:09:07,120 Anybody know what organism has the most genes? 129 00:09:07,120 --> 00:09:12,750 130 00:09:12,750 --> 00:09:15,600 Any guesses? 131 00:09:15,600 --> 00:09:20,430 So plants have the biggest genomes 132 00:09:20,430 --> 00:09:23,640 in terms of overall sequence length. 133 00:09:23,640 --> 00:09:26,880 There is a kind of flea that used to be the big winner. 134 00:09:26,880 --> 00:09:29,280 So there was a flea that had 31,000. 135 00:09:29,280 --> 00:09:35,100 But right now, it's the octopus, 33,000 genes. 136 00:09:35,100 --> 00:09:37,170 They have all these weird N-cadherins 137 00:09:37,170 --> 00:09:40,990 that are involved in their distributive neural network. 138 00:09:40,990 --> 00:09:42,435 It's a really cool kind of thing. 139 00:09:42,435 --> 00:09:45,330 140 00:09:45,330 --> 00:09:49,460 But they have more than we do. 10381

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