1 00:00:01,000 --> 00:00:04,000 So we're shifting gears today. We're going to talk about molecular 2 00:00:04,000 --> 00:00:08,000 evolution, i.e. how do we understand how species 3 00:00:08,000 --> 00:00:12,000 evolve, how do we understand a lot about ourselves, 4 00:00:12,000 --> 00:00:17,000 how human evolution is taking place over the last couple hundred 5 00:00:17,000 --> 00:00:21,000 thousand years. And traditionally, 6 00:00:21,000 --> 00:00:25,000 evolution has been the purview of people who study the morphology of 7 00:00:25,000 --> 00:00:29,000 organisms, and when I talk about morphology, obviously I'm talking 8 00:00:29,000 --> 00:00:34,000 about shape and form. And by comparing organisms, 9 00:00:34,000 --> 00:00:38,000 starting already 250 years ago, one began to develop hierarchies of 10 00:00:38,000 --> 00:00:43,000 how different organisms on the planet are related to one another. 11 00:00:43,000 --> 00:00:47,000 You've seen this, undoubtedly, in high school biology. 12 00:00:47,000 --> 00:00:51,000 This is the study of phylogeny, and phylogeny has traditionally been 13 00:00:57,000 --> 00:01:00,000 figured out by comparing the phenotypes, the morphologies of 14 00:01:00,000 --> 00:01:03,000 adults, sometimes embryonic development, and on that basis, 15 00:01:03,000 --> 00:01:06,000 attempting to extrapolate back in evolutionary time, 16 00:01:06,000 --> 00:01:10,000 about the relatedness of different organisms, one to the other. 17 00:01:10,000 --> 00:01:14,000 And in so doing, one has been able to create, 18 00:01:14,000 --> 00:01:18,000 for example, family trees, here's something that Charles Darwin was 19 00:01:18,000 --> 00:01:22,000 already interested in, the various kinds of finches on the 20 00:01:22,000 --> 00:01:27,000 Galapagos Islands off Peru, in the Pacific. And here, one is 21 00:01:27,000 --> 00:01:31,000 beginning to organize different bird species on the basis of whether 22 00:01:31,000 --> 00:01:35,000 they're more closely or less closely related to one another, 23 00:01:35,000 --> 00:01:39,000 and to draw pedigrees, which, one imagines, describe how they 24 00:01:39,000 --> 00:01:44,000 evolved, one from the other. i.e., organisms which are very 25 00:01:44,000 --> 00:01:48,000 similar to one another must be more closely related evolutionarily, 26 00:01:48,000 --> 00:01:53,000 and conversely, those that appear very differently from one another, 27 00:01:53,000 --> 00:01:58,000 morphologically, must be far more distantly related to one another. 28 00:01:58,000 --> 00:02:02,000 In fact, these kinds of morphologic extrapolations can be very 29 00:02:02,000 --> 00:02:07,000 misleading. So here, for example, are two kinds of eyes. 30 00:02:07,000 --> 00:02:11,000 The top eye is a Drysophila eye 31 00:02:11,000 --> 00:02:14,000 which, to state the obvious, looks a lot different from our eyes, 32 00:02:14,000 --> 00:02:18,000 which is that the chordate eyes shown the bottom. 33 00:02:18,000 --> 00:02:21,000 Totally different. Our rods and cones face backwards, 34 00:02:21,000 --> 00:02:24,000 the Drysophila Arthropod eyes, the light sensors face forward. 35 00:02:24,000 --> 00:02:27,000 Everything is different. And on the basis of that, 36 00:02:27,000 --> 00:02:30,000 you would say that these two organisms are independent 37 00:02:30,000 --> 00:02:34,000 evolutionary inventions, that they've been invented on two 38 00:02:34,000 --> 00:02:37,000 occasions, and that they have no relatedness, one to the 39 00:02:37,000 --> 00:02:41,000 other, at all. But I will tell you an extraordinary 40 00:02:41,000 --> 00:02:45,000 experiment. You can take, there's a master gene that controls 41 00:02:45,000 --> 00:02:50,000 eye development in the fly, Drosophila. It's called eyeless, 42 00:02:50,000 --> 00:02:55,000 if you knock it out then the eye doesn't develop at all. 43 00:02:55,000 --> 00:02:59,000 And you can take out of the mouse, what is apparently a related gene 44 00:02:59,000 --> 00:03:04,000 called small eye, so the fly gene is called eyeless 45 00:03:04,000 --> 00:03:09,000 and the mouse gene is called small eye. And you can put the small-eyed 46 00:03:09,000 --> 00:03:13,000 gene into the Drosophila genome, in a fly that lacks the eyeless gene. 47 00:03:13,000 --> 00:03:18,000 So here we're talking about two 48 00:03:18,000 --> 00:03:22,000 different genes. The fly gene is called eyeless, 49 00:03:22,000 --> 00:03:26,000 the mammalian gene, at least in mouse, is called small eye. 50 00:03:26,000 --> 00:03:30,000 If you knock out this gene in the fly genome, and replace it with this 51 00:03:30,000 --> 00:03:34,000 gene, you get a perfectly normal Drosophila eye. 52 00:03:34,000 --> 00:03:38,000 It's extraordinary. Or you can do the following, 53 00:03:38,000 --> 00:03:42,000 you can arrange it so that the mouse small eye gene is expressed 54 00:03:42,000 --> 00:03:46,000 ectopically. When I say ectopically, 55 00:03:46,000 --> 00:03:51,000 I mean that it's expressed in the wrong place, at the wrong time. 56 00:03:51,000 --> 00:03:56,000 So you can do the following experiment. In a fly genome, 57 00:03:56,000 --> 00:04:00,000 you can arrange it so that the mouse small eye gene becomes expressed on 58 00:04:00,000 --> 00:04:05,000 one of the extremities of the fly, on one of the legs of the fly. And 59 00:04:05,000 --> 00:04:10,000 now, on one of the extremities of the fly, an ectopic eye will develop, 60 00:04:10,000 --> 00:04:15,000 looks just like a Drosophila eye, but it's development is programmed 61 00:04:15,000 --> 00:04:19,000 by the mouse small eye gene. What I'm telling you is that these 62 00:04:19,000 --> 00:04:23,000 two genes are totally interchangeable, 63 00:04:23,000 --> 00:04:27,000 that they are effectively indistinguishable from one another, 64 00:04:27,000 --> 00:04:31,000 functionally they have some sequence relatedness, but in terms of the way 65 00:04:31,000 --> 00:04:34,000 they program development, they are effectively equivalent. 66 00:04:34,000 --> 00:04:38,000 And what this means is that the progenitor of these two genes 67 00:04:38,000 --> 00:04:42,000 must've already existed at the time that the flies and we diverged, 68 00:04:42,000 --> 00:04:46,000 which six or seven-hundred million years ago, and in the intervening 69 00:04:46,000 --> 00:04:50,000 six or seven-hundred million years, these genes have been totally 70 00:04:50,000 --> 00:04:53,000 unchanged. i.e., once the gene was developed, 71 00:04:53,000 --> 00:04:57,000 evolution could not tinker with it, and begin to change it in different 72 00:04:57,000 --> 00:05:00,000 ways, ostensibly because such tinkering would render these genes 73 00:05:00,000 --> 00:05:04,000 dysfunctional, and thereby would inactivate them, 74 00:05:04,000 --> 00:05:08,000 thereby depriving the organism of a critical sensory organ. 75 00:05:08,000 --> 00:05:11,000 So here we have an example, a dramatic example, of how 76 00:05:11,000 --> 00:05:15,000 morphology misleads us. Here we have an example of where we 77 00:05:15,000 --> 00:05:18,000 would say these two eyes, the two eyes I've shown you here, 78 00:05:18,000 --> 00:05:22,000 are so different from one another that they must, 79 00:05:22,000 --> 00:05:26,000 by necessity, be independent evolutionary inventions. 80 00:05:26,000 --> 00:05:29,000 But in fact, genetics tells us, and these gene-swapping experiments, 81 00:05:29,000 --> 00:05:33,000 tell us that the two eyes descend from a common ancestral eye, 82 00:05:33,000 --> 00:05:37,000 a prototypical eye, whose precise morphology we can't discern anymore. 83 00:05:37,000 --> 00:05:41,000 And so we begin to realize that if we really want to understand 84 00:05:41,000 --> 00:05:44,000 evolution and we really want to understand phylogeny, 85 00:05:44,000 --> 00:05:48,000 phylogeny being how the species are related to one another, 86 00:05:48,000 --> 00:05:52,000 we have to the DNA, and we have to begin to look not at phenotype, 87 00:05:52,000 --> 00:05:56,000 but we have to look instead, at genotype. 88 00:05:56,000 --> 00:06:01,000 The Darwinian model is pretty much like this, the survival of the 89 00:06:01,000 --> 00:06:06,000 fittest. And when I say that, we imagine that we have here, a 90 00:06:06,000 --> 00:06:11,000 genetically heterogeneous group of organisms within a species, 91 00:06:11,000 --> 00:06:16,000 and this, this number of individuals in the species could be 100, 92 00:06:16,000 --> 00:06:22,000 it could be 1,000,000. This particular individual, 93 00:06:22,000 --> 00:06:27,000 by chance, acquires a mutation, or an advantageous allele, through 94 00:06:27,000 --> 00:06:32,000 some genetic alteration. This genotype renders this organism 95 00:06:32,000 --> 00:06:36,000 more fit, phenotypically, has a selective advantage and 96 00:06:36,000 --> 00:06:40,000 consequently, over extended periods of time, which may be thousands or 97 00:06:40,000 --> 00:06:44,000 even millions of years, the descendents of the organism 98 00:06:44,000 --> 00:06:48,000 bearing this allele now have advantage, have greater reproductive 99 00:06:48,000 --> 00:06:52,000 advantage, survival advantage, compared with the other individuals 100 00:06:52,000 --> 00:06:56,000 in the same species, and therefore, the representation of 101 00:06:56,000 --> 00:07:00,000 this mutant allele in the gene pool of the species becomes expanded. 102 00:07:00,000 --> 00:07:03,000 When I say gene pool, I'm talking bout the common shared 103 00:07:03,000 --> 00:07:07,000 set of genes within the species, such as within the human species. 104 00:07:07,000 --> 00:07:10,000 And so eventually, the descendents of this organism, 105 00:07:10,000 --> 00:07:14,000 or the descendants of an organism bearing this allele, 106 00:07:14,000 --> 00:07:17,000 now become overrepresented in the population, because they're more fit. 107 00:07:17,000 --> 00:07:21,000 And then there can be another succession, i. 108 00:07:21,000 --> 00:07:24,000 ., there could be other mutations occurring subsequently. 109 00:07:24,000 --> 00:07:28,000 Once again, favoring the selective outgrowth of an individual bearing 110 00:07:28,000 --> 00:07:31,000 this allele, or this allele. And in addition, 111 00:07:31,000 --> 00:07:35,000 there can be the process of what one calls, speciation. 112 00:07:35,000 --> 00:07:38,000 That is to say, that if some parts of the species live in one place, 113 00:07:38,000 --> 00:07:42,000 and other parts of the species live in another place, 114 00:07:42,000 --> 00:07:45,000 geographically, they may no longer interbreed, and as a consequence, 115 00:07:45,000 --> 00:07:49,000 and because of the fact they're under different selective pressures, 116 00:07:49,000 --> 00:07:52,000 they may begin to diverge from another if, evolutionary speaking, 117 00:07:52,000 --> 00:07:56,000 because they're no longer actively exchanging genes within one another. 118 00:07:56,000 --> 00:08:00,000 And, as a consequence, one can have new species arriving. 119 00:08:00,000 --> 00:08:03,000 And what one believes, this happens over slow, 120 00:08:03,000 --> 00:08:07,000 slowly over evolutionary time, but it does arise, and to the extent 121 00:08:07,000 --> 00:08:11,000 it does, one eventually ends up with organisms here and here, 122 00:08:11,000 --> 00:08:15,000 which can no longer effectively interbreed with one another. 123 00:08:15,000 --> 00:08:18,000 That is to say, they become genetically so different from one 124 00:08:18,000 --> 00:08:22,000 another, that any hybrids formed between them are, 125 00:08:22,000 --> 00:08:26,000 in fact, sterile, for one reason or another, if they're at all 126 00:08:26,000 --> 00:08:30,000 interested in breeding with one another to begin with. 127 00:08:30,000 --> 00:08:33,000 And what this means is that we can begin to trace how closely or 128 00:08:33,000 --> 00:08:37,000 distantly related species are to one another, simply by asking how 129 00:08:37,000 --> 00:08:40,000 closely or similarly related are their DNA sequences? 130 00:08:40,000 --> 00:08:44,000 If, distantly related organisms have very distantly related 131 00:08:44,000 --> 00:08:48,000 sequences, and closely related organisms must have sequences which 132 00:08:48,000 --> 00:08:51,000 are very similar to one another. And over evolutionary time, there's 133 00:08:51,000 --> 00:08:55,000 a so-called mutational clock, where one, where each species 134 00:08:55,000 --> 00:08:59,000 accumulates a certain number of point mutations, 135 00:08:59,000 --> 00:09:02,000 base substitutions in it's DNA, per million years, and the longer 136 00:09:02,000 --> 00:09:06,000 the two species are separated from one another, the greater will be the 137 00:09:06,000 --> 00:09:10,000 difference in their sequence diversity. 138 00:09:10,000 --> 00:09:14,000 And on that simple basis, one can begin to construct 139 00:09:14,000 --> 00:09:18,000 evolutionary trees of, for example, the entire cellular 140 00:09:18,000 --> 00:09:22,000 life on the planet. And here's such an evolutionary 141 00:09:22,000 --> 00:09:27,000 tree, where what's being compared is the ribosomal RNA sequences, 142 00:09:27,000 --> 00:09:31,000 i.e., the small ribosomal RNA. Remember, ribosomes have two 143 00:09:31,000 --> 00:09:35,000 subunits, small and large, in the case of prokaryotes, 144 00:09:35,000 --> 00:09:39,000 it's 16S RNA, that is, it's sedimentation rate. 145 00:09:39,000 --> 00:09:43,000 In the case of mammals, it's 18S. In both cases, 146 00:09:43,000 --> 00:09:47,000 these are small ribosomal RNA subunits. The ribosome was only 147 00:09:47,000 --> 00:09:51,000 invented on one occasion during the evolution of life on the planet, 148 00:09:51,000 --> 00:09:55,000 so one can begin to compare since all cellular life forms have life 149 00:09:55,000 --> 00:09:58,000 forms, one can ask how similar, or dissimilar, are the various 150 00:09:58,000 --> 00:10:02,000 sequences and coding, in small ribosomal RNA subunits? 151 00:10:02,000 --> 00:10:06,000 And on the basis of that, one has concluded that there are actually 152 00:10:06,000 --> 00:10:10,000 three branches of cellular life on the planet. 153 00:10:10,000 --> 00:10:13,000 The bacteria indicated here, this is not such a great Xerox, 154 00:10:13,000 --> 00:10:17,000 where you see a whole series of different kinds of bacteria, 155 00:10:17,000 --> 00:10:20,000 indicated on this tree. Sorry about the poor reproduction. 156 00:10:20,000 --> 00:10:24,000 Here there's a dashed line indicating that we're talking, 157 00:10:24,000 --> 00:10:28,000 there's a second kingdom in the middle here, indicated by what are 158 00:10:28,000 --> 00:10:31,000 called archae, and the archae are also, 159 00:10:31,000 --> 00:10:35,000 from our point of view, prokaryotes, but they're not bacteria. They are 160 00:10:35,000 --> 00:10:39,000 a single-cell life form, they're often found in unusual 161 00:10:39,000 --> 00:10:42,000 situations, for instance, in thermal vents in the bottom of 162 00:10:42,000 --> 00:10:46,000 the ocean floor, some of them are able to stand high 163 00:10:46,000 --> 00:10:50,000 salt, some of them are able to stand high temperature, 164 00:10:50,000 --> 00:10:54,000 like therma fillus, therma proteus, and so fourth. 165 00:10:54,000 --> 00:10:58,000 And these, their ribosomal RNAs, are so different from those of 166 00:10:58,000 --> 00:11:02,000 bacteria, that they've been placed in their own separate kingdom. 167 00:11:02,000 --> 00:11:06,000 And finally, here are the eukaryotes, all over here. 168 00:11:06,000 --> 00:11:10,000 These are all eukaryotic cells, starting here. And we, our cells, 169 00:11:10,000 --> 00:11:14,000 seem to be slightly more closely related to those of the Archaea, 170 00:11:14,000 --> 00:11:18,000 if you follow this ribosomal sequences, than they are to 171 00:11:18,000 --> 00:11:22,000 the actual bacteria. So, there's actually two major 172 00:11:22,000 --> 00:11:26,000 prokaryotic life forms on the planet. The first living organism, 173 00:11:26,000 --> 00:11:30,000 well if you begin to try to look back in geological record, 174 00:11:30,000 --> 00:11:34,000 it looks like the first living cellular life forms existed already 175 00:11:34,000 --> 00:11:38,000 3-3.5 billion years ago, not so long after the planet was 176 00:11:38,000 --> 00:11:42,000 formed, which was between 4. and 4.5 billion years ago. And 177 00:11:42,000 --> 00:11:46,000 here's the whole eukaryotic tree, and if we look at the eukaryotic 178 00:11:46,000 --> 00:11:50,000 trees, remembering here that we're starting at 3.5 billion years ago, 179 00:11:50,000 --> 00:11:53,000 And we're using this evolutionary clock to determine relatedness, 180 00:11:53,000 --> 00:11:56,000 then we see a whole series of single-cell eukaryotes, 181 00:11:56,000 --> 00:12:00,000 here are their names are, these are protozoan, eukaryotic 182 00:12:00,000 --> 00:12:03,000 protozoan. Here's Amoeba, here are slime molds, here are 183 00:12:03,000 --> 00:12:07,000 cilliates, we're still at single-cell organisms. 184 00:12:07,000 --> 00:12:10,000 Finally we get to multi-cellular organisms, plants, 185 00:12:10,000 --> 00:12:14,000 fungi, and animals, and so, all animals on the planet 186 00:12:14,000 --> 00:12:17,000 are a relatively recent invention. All animals, all of the metazoan, 187 00:12:17,000 --> 00:12:21,000 are just on this very small branch, and we know that this very small 188 00:12:21,000 --> 00:12:25,000 branch started around 600-650 million years ago, 189 00:12:25,000 --> 00:12:29,000 maybe 700 million years ago. And that was the time, roughly 190 00:12:29,000 --> 00:12:32,000 speaking, when we and flies last had our common ancestor, 191 00:12:32,000 --> 00:12:36,000 otherwise, to state the obvious, we and flies are very different. 192 00:12:36,000 --> 00:12:40,000 The fact that the gene for encoding the eye has been conserved, 193 00:12:40,000 --> 00:12:44,000 so faithfully, over enormous evolutionary period of time 194 00:12:44,000 --> 00:12:48,000 indicates something else, And that is, certain genes can 195 00:12:48,000 --> 00:12:52,000 evolve progressively over a long period of time, 196 00:12:52,000 --> 00:12:57,000 because they don't encode vital functions, or they may even be 197 00:12:57,000 --> 00:13:02,000 sequences between genes that don't encode phenotype at all. 198 00:13:02,000 --> 00:13:06,000 Imagine, for example, we have a situation were here we have a gene 199 00:13:06,000 --> 00:13:11,000 which encodes a vital function, like the eye, here's another gene 200 00:13:11,000 --> 00:13:16,000 that encodes another function, oh I don't know, a leg. 201 00:13:16,000 --> 00:13:19,000 And here we have intergenic sequences. After all, 202 00:13:19,000 --> 00:13:23,000 as you have learned by now, more than 96% of the DNA in our 203 00:13:23,000 --> 00:13:27,000 genome, doesn't encode proteins, and probably isn't even responsible 204 00:13:27,000 --> 00:13:31,000 for regulating genes. So these sequences, right in here, 205 00:13:31,000 --> 00:13:34,000 can mutate freely during the course of evolution, without having a 206 00:13:34,000 --> 00:13:38,000 deleterious effect on the phenotype of the organism. 207 00:13:38,000 --> 00:13:42,000 There's no evolutionary pressure to constrain the evolution of these 208 00:13:42,000 --> 00:13:46,000 genes, but if this gene over here encodes an eyes, 209 00:13:46,000 --> 00:13:49,000 And if this gene has been optimized in it's sequence, 210 00:13:49,000 --> 00:13:53,000 early in the course of evolution, that any subsequently occurring 211 00:13:53,000 --> 00:13:57,000 mutations will compromise it's function, and therefore there's 212 00:13:57,000 --> 00:14:00,000 enormous selective pressure to eliminate any organism which has 213 00:14:00,000 --> 00:14:04,000 begun to tinker with the sequence of this gene, by changing it's sequence. 214 00:14:04,000 --> 00:14:08,000 Here, in stark contrast, there's no such selective pressure. 215 00:14:08,000 --> 00:14:11,000 The organism, that is, 216 00:14:11,000 --> 00:14:14,000 can tinker at will with this. I don't mean literally that the 217 00:14:14,000 --> 00:14:18,000 organism is able to tinker with it's own DNA sequences, 218 00:14:18,000 --> 00:14:21,000 but the hand of evolution can change these sequences in here, 219 00:14:21,000 --> 00:14:24,000 at will, without having any effect on the viability of the organism on 220 00:14:24,000 --> 00:14:27,000 it's selective, or Darwinian, fitness, 221 00:14:27,000 --> 00:14:30,000 and therefore, such mutations in these, in these sequences, 222 00:14:30,000 --> 00:14:34,000 are neutral mutation, they have on effect on phenotype, 223 00:14:34,000 --> 00:14:37,000 and they will not be eliminated from the gene pool. 224 00:14:37,000 --> 00:14:40,000 Again here, mutations in these vital, critical genes will be 225 00:14:40,000 --> 00:14:43,000 eliminated from the gene pool. So that's another one of the 226 00:14:43,000 --> 00:14:46,000 principles in molecular evolution that we want to talk about. 227 00:14:46,000 --> 00:14:50,000 And if you follow these principles, we can not only do, draw 228 00:14:50,000 --> 00:14:53,000 evolutionary trees like this, which have a grand scope, a scale of 229 00:14:53,000 --> 00:14:56,000 three and a half billion years, we can talk, for example, about how 230 00:14:56,000 --> 00:15:00,000 different kinds of bears are related to one another, 231 00:15:00,000 --> 00:15:03,000 and on the basis, once again, of their DNA sequence. 232 00:15:03,000 --> 00:15:06,000 Or, if you want, we can even look at how different kinds of 233 00:15:06,000 --> 00:15:10,000 domesticated animals are related to one another. 234 00:15:10,000 --> 00:15:14,000 This is kind of a fun undertaking. Look at this. Why is it fun? Well 235 00:15:14,000 --> 00:15:19,000 it's, it's kind of an amusing idea, how often were cows domesticated 236 00:15:19,000 --> 00:15:23,000 during the history of humanity? How often were sheep domesticated? 237 00:15:23,000 --> 00:15:28,000 Pigs, water buffalos, and horses. And what you see here is that cattle 238 00:15:28,000 --> 00:15:32,000 were domesticated on two occasions, probably once in Western Asia, the 239 00:15:32,000 --> 00:15:37,000 middle east, and once in Eastern Asia. Sheep were domesticated twice, 240 00:15:37,000 --> 00:15:42,000 all modern sheep following these two families here. 241 00:15:42,000 --> 00:15:46,000 Obviously they share a common ancestor someway back, 242 00:15:46,000 --> 00:15:50,000 but most sheep either fall here or here. Pigs seem to have been 243 00:15:50,000 --> 00:15:54,000 domesticated twice, once over here and once over here, 244 00:15:54,000 --> 00:15:58,000 water buffalos twice, horses are very confusing, 245 00:15:58,000 --> 00:16:02,000 it looks like they were domesticated on several occasions because they're 246 00:16:02,000 --> 00:16:06,000 all over the map, they're not two clusters of 247 00:16:06,000 --> 00:16:10,000 closely-related varieties, like here and here. What others, 248 00:16:10,000 --> 00:16:14,000 dogs, that's recently, I forget what the number is for dogs, once. 249 00:16:14,000 --> 00:16:18,000 Dogs were domesticated once, probably the earliest domestication, 250 00:16:18,000 --> 00:16:22,000 about 100,000 years ago. They all have one common radiating tree, 251 00:16:22,000 --> 00:16:26,000 here we have two radiating trees, one cluster over here, one cluster 252 00:16:26,000 --> 00:16:31,000 over here, with sheep, pigs, and so fourth. So we can even, 253 00:16:31,000 --> 00:16:35,000 so you can learn an enormous amount about even the history of 254 00:16:35,000 --> 00:16:40,000 agriculture, by looking at these kinds of DNA pedigree. 255 00:16:40,000 --> 00:16:44,000 Here's some other interesting principles. Mitochondrial DNA 256 00:16:44,000 --> 00:16:49,000 passes always from the mother, so when a fertilized egg is formed, 257 00:16:49,000 --> 00:16:53,000 Dad gives his chromosomes, but he doesn't donate for any, 258 00:16:53,000 --> 00:16:58,000 doesn't donate any mitochondrial DNA. I remember visiting a friend in 259 00:16:58,000 --> 00:17:03,000 North Carolina in 1974, and he was looking at the 260 00:17:03,000 --> 00:17:07,000 mitochondrial DNA of mules and, when you breed a horse and a donkey, 261 00:17:07,000 --> 00:17:12,000 what do you get out? You get a mule out, 262 00:17:12,000 --> 00:17:18,000 or, what happens if you do it the other way? What happens if the 263 00:17:18,000 --> 00:17:24,000 father is a horse, and the mother is a donkey? 264 00:17:24,000 --> 00:17:30,000 It's a hinny, it's actually called a hinny. So there's two ways of 265 00:17:30,000 --> 00:17:36,000 breeding, and the question is now, and by the way, it's not so nice to 266 00:17:36,000 --> 00:17:42,000 have a father being the horse and the mother being the mule. 267 00:17:42,000 --> 00:17:45,000 Why? Because Mom isn't used to carrying an embryo that's much 268 00:17:45,000 --> 00:17:49,000 larger than she's adapted to. The other way is fine, because then 269 00:17:49,000 --> 00:17:53,000 she can carry a small embryo, but if Dad comes from a much larger 270 00:17:53,000 --> 00:17:57,000 species, then the fetus that the female donkey must carry, 271 00:17:57,000 --> 00:18:00,000 is larger than her womb is really evolved to carry. 272 00:18:00,000 --> 00:18:04,000 So, you don't often see these hinnies around because they cause 273 00:18:04,000 --> 00:18:08,000 great difficulty at birth. In any case, why did I get into 274 00:18:08,000 --> 00:18:12,000 this digression? Glad I asked that. 275 00:18:12,000 --> 00:18:15,000 The question was, where did the mitochondrial DNA come? 276 00:18:15,000 --> 00:18:19,000 1974, this was still a hot question. And it turned out, 277 00:18:19,000 --> 00:18:22,000 the mitochondrial DNA in both the mules and the hinnies came always 278 00:18:22,000 --> 00:18:26,000 from Mom. There was not a trace of mitochondrial DNA from the father 279 00:18:26,000 --> 00:18:29,000 and, as a consequence, this begins to cause us to realize 280 00:18:29,000 --> 00:18:33,000 where our mitochondrial DNA comes from. So his mitochondrial DNA 281 00:18:33,000 --> 00:18:36,000 comes from his mother, his maternal grandmother, 282 00:18:36,000 --> 00:18:40,000 her mother, her mother before her, and so fourth, and the same for each 283 00:18:40,000 --> 00:18:43,000 one of you. And what this means is that if you 284 00:18:43,000 --> 00:18:47,000 look at a pedigree like this, and for example, here we have a 285 00:18:47,000 --> 00:18:50,000 mother and a father, girls are always round, 286 00:18:50,000 --> 00:18:54,000 boys are square. And here you'll see the mitochondrial DNA, 287 00:18:54,000 --> 00:18:57,000 it's donated to all of the children, but the fact is that these boys, 288 00:18:57,000 --> 00:19:01,000 when they mate, when they have offspring, 289 00:19:01,000 --> 00:19:05,000 they will no longer pass along her mitochondrial DNA, 290 00:19:05,000 --> 00:19:08,000 so it will be lost. And the only way the mitochondrial 291 00:19:08,000 --> 00:19:12,000 DNA can be transmitted is through one of her daughters, 292 00:19:12,000 --> 00:19:16,000 who in turn, have daughters. Here you see the situation where 293 00:19:16,000 --> 00:19:20,000 almost all of her mitochondrial DNA is lost, except for this female 294 00:19:20,000 --> 00:19:24,000 descendent who, once again, passes it on to her sons 295 00:19:24,000 --> 00:19:28,000 and daughters. Only the daughters, 296 00:19:28,000 --> 00:19:33,000 again, can transmit mitochondrial DNA. And there is equity in life, 297 00:19:33,000 --> 00:19:37,000 it doesn't often happen. Jack Kennedy said life is unfair, 298 00:19:37,000 --> 00:19:41,000 but sometimes it's reasonably fair, but here is the y-chromosomes, the 299 00:19:41,000 --> 00:19:46,000 y-counterpart. Keep in mind, the y-chromosome only 300 00:19:46,000 --> 00:19:50,000 passes from father-to-son, to father-to-son, and exactly the 301 00:19:50,000 --> 00:19:54,000 same dynamics apply. And importantly, this is critical 302 00:19:54,000 --> 00:19:58,000 for our thinking now, neither the y-chromosome nor the 303 00:19:58,000 --> 00:20:02,000 mitochondrial DNA recombines with another chromosome. 304 00:20:02,000 --> 00:20:06,000 And therefore, the complexities of diploid mendelian genetics are 305 00:20:06,000 --> 00:20:10,000 obviated. So when you're looking at, for example, the mitochondrial DNA, 306 00:20:10,000 --> 00:20:14,000 you can look at the pure results of accumulated mutations, 307 00:20:14,000 --> 00:20:17,000 You don't have to worry about crossing-over, 308 00:20:17,000 --> 00:20:21,000 you don't have to worry about exchange of portions of a gene 309 00:20:21,000 --> 00:20:25,000 between two homologous chromosomes. It doesn't happen with the 310 00:20:25,000 --> 00:20:29,000 y-chromosome because there's only one of them in the cell, 311 00:20:29,000 --> 00:20:33,000 and it doesn't happen with the mitochondrial DNA because there's no 312 00:20:33,000 --> 00:20:37,000 other DNA for it to equilibrate with. As a consequence, 313 00:20:37,000 --> 00:20:41,000 we can begin to think about what happens with mitochondrial DNA and 314 00:20:41,000 --> 00:20:45,000 y-chromosomal DNA, in young and old species. 315 00:20:45,000 --> 00:20:48,000 So let's talk about a recently formed species, 316 00:20:48,000 --> 00:20:52,000 and let's say we have a young species down here, 317 00:20:52,000 --> 00:20:55,000 below the illustration, and now this species, which has 318 00:20:55,000 --> 00:20:59,000 recently come into existence for whatever reason, 319 00:20:59,000 --> 00:21:02,000 hangs around for the next couple million years. 320 00:21:02,000 --> 00:21:06,000 And while it hangs around, there will be random mutations, 321 00:21:06,000 --> 00:21:10,000 which strike the genomes of individual members of that species. 322 00:21:10,000 --> 00:21:14,000 And therefore, the longer the life of the species 323 00:21:14,000 --> 00:21:18,000 as a whole, the more genetically diverse will become the individuals 324 00:21:18,000 --> 00:21:22,000 in the species, and therefore, this species will 325 00:21:22,000 --> 00:21:26,000 grow to have more and more genetic diversity, just because of the 326 00:21:26,000 --> 00:21:30,000 random stochastic mutations that accumulate in different peoples 327 00:21:30,000 --> 00:21:34,000 genomes in the course of the life of this species, over millions of years. 328 00:21:34,000 --> 00:21:38,000 Again, keep in mind that the vast majority of these accumulated 329 00:21:38,000 --> 00:21:42,000 mutations will be mutual mutations, which will not affect phenotype, and 330 00:21:42,000 --> 00:21:46,000 therefore, they will not be eliminated by Darwinian selection. 331 00:21:46,000 --> 00:21:50,000 And many of these neutral mutations, which have no effect on organismic 332 00:21:50,000 --> 00:21:54,000 fitness, but are simply evolutionary neutral, are sometimes called 333 00:21:54,000 --> 00:21:59,000 polymorphisms. The term polymorphism, 334 00:21:59,000 --> 00:22:03,000 -morph is once again morphology, derives from the fact that species 335 00:22:03,000 --> 00:22:07,000 tend to be polymorphic, we don't all have blond hair, 336 00:22:07,000 --> 00:22:11,000 we don't all have brown eyes. We, as a species, 337 00:22:11,000 --> 00:22:15,000 have a great variability in phenotype, we're polymorphic, 338 00:22:15,000 --> 00:22:18,000 and yet having black hair, and having blond hair, 339 00:22:18,000 --> 00:22:22,000 and having red hair, none of those is considered mutant, 340 00:22:22,000 --> 00:22:25,000 none of those is considered pathological. I. 341 00:22:25,000 --> 00:22:29,000 ., among the group of normal phenotypes, there's a whole series 342 00:22:29,000 --> 00:22:32,000 of different gradations, and these are considered normal 343 00:22:32,000 --> 00:22:36,000 gradations in phenotype, but at the genetic level, 344 00:22:36,000 --> 00:22:40,000 we talk about polymorphisms in the same sense. 345 00:22:40,000 --> 00:22:43,000 Genetically distinct nucleotide sequences, which again, 346 00:22:43,000 --> 00:22:47,000 are not pathological, they don't create a disadvantageous phenotype. 347 00:22:47,000 --> 00:22:51,000 And as a consequence, they are once again, not selected against. 348 00:22:51,000 --> 00:22:54,000 Now look what happens over here. Here we have great genetic 349 00:22:54,000 --> 00:22:58,000 diversity, but what will happen is, for one reason or another, only a 350 00:22:58,000 --> 00:23:02,000 small subset of individuals constituting this species, 351 00:23:02,000 --> 00:23:06,000 will turn out to be the ancestors of the successor species. 352 00:23:06,000 --> 00:23:09,000 Here's the next species that arises. And why will these just be the 353 00:23:09,000 --> 00:23:13,000 ancestors? Well, everybody else could get killed off 354 00:23:13,000 --> 00:23:16,000 through some plague, they might get killed off by 355 00:23:16,000 --> 00:23:20,000 somebody going out and purposefully killing them, or, 356 00:23:20,000 --> 00:23:23,000 it might just be that a meteor comes down and wipes all these guys out, 357 00:23:23,000 --> 00:23:27,000 and these are the only ones in here, from this small subset of the 358 00:23:27,000 --> 00:23:31,000 original species, who end up surviving, 359 00:23:31,000 --> 00:23:34,000 and who end up becoming the precursors, the ancestors, 360 00:23:34,000 --> 00:23:38,000 of the new species, and once again, undergoes a period of 361 00:23:38,000 --> 00:23:42,000 diversification. And what we have therefore, 362 00:23:42,000 --> 00:23:46,000 is a diversification and then a collapse of genetic diversity. 363 00:23:46,000 --> 00:23:50,000 Here, this species, because it came from a small group, 364 00:23:50,000 --> 00:23:54,000 is initially rather, rather homogenous genetically, 365 00:23:54,000 --> 00:23:59,000 but with the passage of evolutionary time, once again, 366 00:23:59,000 --> 00:24:03,000 there's evolutionary diversification. So, an older species actually ends 367 00:24:03,000 --> 00:24:07,000 up being much more genetically diverse than does the 368 00:24:07,000 --> 00:24:12,000 younger species. If you look at two chimpanzees 369 00:24:12,000 --> 00:24:16,000 living on opposite sides of the same hill in West Africa, 370 00:24:16,000 --> 00:24:20,000 they are genetically far more distantly related to one another, 371 00:24:20,000 --> 00:24:24,000 than any one of us, by a factor of 10 to 15. Two chimpanzees, 372 00:24:24,000 --> 00:24:28,000 they look exactly the same, they have the same peculiar habits, 373 00:24:28,000 --> 00:24:32,000 but they're genetically far more distantly-related than we are to 374 00:24:32,000 --> 00:24:36,000 one-another, than I am to any one of you, or than any one of you is to 375 00:24:36,000 --> 00:24:40,000 one another. And what does that mean? 376 00:24:40,000 --> 00:24:45,000 It means that, roughly speaking, 377 00:24:45,000 --> 00:24:50,000 the species of chimpanzees is, at least, 10 or 15 times older than 378 00:24:50,000 --> 00:24:56,000 our species are. We're a young species, 379 00:24:56,000 --> 00:25:01,000 chimpanzees probably first speciated three or four million years ago, 380 00:25:01,000 --> 00:25:07,000 if the paleontological record is, is accurate. Paleontology is the 381 00:25:07,000 --> 00:25:12,000 study of old, dusty bones, so you can begin to imagine when 382 00:25:12,000 --> 00:25:18,000 chimpanzee bones become recognizable in the earth. 383 00:25:18,000 --> 00:25:22,000 So a paleontologist says that, that chimps aren't that old, and it 384 00:25:22,000 --> 00:25:27,000 begins to suggest that our species is only about 200, 385 00:25:27,000 --> 00:25:32,000 00 years old, at the oldest. Now you say 200,000 years is a long 386 00:25:32,000 --> 00:25:36,000 time, but it isn't so long because I started out this discussion talking 387 00:25:36,000 --> 00:25:41,000 about 3.5 billion years, 3.5 times ten to the ninth, 388 00:25:41,000 --> 00:25:46,000 and now I'm talking about two times ten to the fourth. 389 00:25:46,000 --> 00:25:51,000 Is that right? No, two times ten to the fifth. 390 00:25:51,000 --> 00:25:55,000 Four orders of magnitude difference. So that means that our species, we 391 00:25:55,000 --> 00:25:59,000 went through a bottleneck about 200-250,000 years ago, 392 00:25:59,000 --> 00:26:04,000 and because that is so recent, we haven't had a chance to actually 393 00:26:04,000 --> 00:26:08,000 acquire much genetic diversity. We're actually very closely related 394 00:26:08,000 --> 00:26:12,000 to one another, although to talk to people, 395 00:26:12,000 --> 00:26:17,000 you'd think we were all very distantly related to one another. 396 00:26:17,000 --> 00:26:21,000 Here's another interesting notion, which also figures in, and that is, 397 00:26:21,000 --> 00:26:26,000 what happens in the genetics of small populations? 398 00:26:26,000 --> 00:26:30,000 So here we started out with eight individuals, and let's assume for a 399 00:26:30,000 --> 00:26:34,000 moment, that this population has a steady size, i. 400 00:26:34,000 --> 00:26:38,000 . it doesn't increase or decrease over the course of several 401 00:26:38,000 --> 00:26:42,000 generations. And what that means is that each couple will, 402 00:26:42,000 --> 00:26:46,000 on average, leave behind two children, and those two children 403 00:26:46,000 --> 00:26:50,000 will breed, and each of them will, couples in the successor population, 404 00:26:50,000 --> 00:26:54,000 will leave behind two children. And what you see already, 405 00:26:54,000 --> 00:26:58,000 in such small populations, is that for example, this male here 406 00:26:58,000 --> 00:27:02,000 has two girls, and right away, 407 00:27:02,000 --> 00:27:06,000 to the extent he had an interesting y-chromosome, that y-chromosome was 408 00:27:06,000 --> 00:27:10,000 lost from the gene pool. This girl, here, had an interesting 409 00:27:10,000 --> 00:27:14,000 mitochondrial DNA, but right away that's lost, 410 00:27:14,000 --> 00:27:18,000 because she has, she has just two boys. And what you see, 411 00:27:18,000 --> 00:27:22,000 in very rapid order, in small populations, there's a 412 00:27:22,000 --> 00:27:26,000 homogenization of the genetic compliment, just because the alleles 413 00:27:26,000 --> 00:27:30,000 are lost within what's called, genetic drift. 414 00:27:30,000 --> 00:27:34,000 And as a consequence, very rapidly, there becomes 415 00:27:34,000 --> 00:27:38,000 homozygosity at many loci in very small populations. 416 00:27:38,000 --> 00:27:42,000 A real-life situation comes from Mutiny on the Bounty, 417 00:27:42,000 --> 00:27:46,000 where Fletcher Christian ends up getting shipwrecked on, 418 00:27:46,000 --> 00:27:50,000 what island was it, Pitcairn Island, which is somewhere on the South 419 00:27:50,000 --> 00:27:54,000 Pacific, South Atlantic, I forget where. Anyhow, today if 420 00:27:54,000 --> 00:27:58,000 you go to Pitcairn Island, almost everybody is called, 421 00:27:58,000 --> 00:28:02,000 almost everybody has a family name, Christian. 422 00:28:02,000 --> 00:28:05,000 Why? Was it that he was more studly and fecund than everybody else? 423 00:28:05,000 --> 00:28:08,000 Probably not. What probably happened was, in the same dynamics 424 00:28:08,000 --> 00:28:12,000 that dictates the homogenization of y-chromosomes, 425 00:28:12,000 --> 00:28:15,000 dictates the homogenization of family names. So, 426 00:28:15,000 --> 00:28:18,000 if you isolate people in a small demographic isolate, 427 00:28:18,000 --> 00:28:22,000 like an island in the middle of the ocean, over a period of generations, 428 00:28:22,000 --> 00:28:25,000 roughly equal to, I think, twice the number of individuals in the steady, 429 00:28:25,000 --> 00:28:28,000 state population, everybody will have the same family name, 430 00:28:28,000 --> 00:28:32,000 because the other family names will, by chance, in a small population, 431 00:28:32,000 --> 00:28:36,000 just be lost. On my father's side of the family, 432 00:28:36,000 --> 00:28:40,000 I have hundreds of cousins with my family name, and on my mother's side 433 00:28:40,000 --> 00:28:44,000 of the family, not a single one, 434 00:28:44,000 --> 00:28:48,000 just as an example of this kind of trait. Now keep in mind that this 435 00:28:48,000 --> 00:28:52,000 evolutionary diversification can also affect the y-chromosome, 436 00:28:52,000 --> 00:28:56,000 so therefore, there are different y-chromosomes across the face of the 437 00:28:56,000 --> 00:29:00,000 planet, which can be distinguished, not because they're better or lesser 438 00:29:00,000 --> 00:29:04,000 y-chromosomes, in terms of the phenotype of 439 00:29:04,000 --> 00:29:08,000 maleness, but because they've accumulated polymorphisms 440 00:29:08,000 --> 00:29:12,000 over a period of time. They may be single-nucleotide 441 00:29:12,000 --> 00:29:16,000 polymorphisms, but these single-nucleotide 442 00:29:16,000 --> 00:29:20,000 polymorphisms can be used to determine how closely, 443 00:29:20,000 --> 00:29:24,000 or distantly related, are individuals to one another. 444 00:29:24,000 --> 00:29:28,000 Let's look at the mitochondrial DNA of women in western Europe, 445 00:29:28,000 --> 00:29:33,000 and if you look at the mitochondrial DNA of women in western Europe, 446 00:29:33,000 --> 00:29:37,000 you find that they only have, how many different things there? 447 00:29:37,000 --> 00:29:41,000 One, two, three, four, five, six, seven, there's seven basic 448 00:29:41,000 --> 00:29:45,000 types of mitochondrial DNA that are found in western and northern 449 00:29:45,000 --> 00:29:50,000 European women. And what that means is, 450 00:29:50,000 --> 00:29:55,000 inescapably, people who live in modern-day Europe, 451 00:29:55,000 --> 00:30:00,000 descend from seven women who had these respective mitochondrial DNA 452 00:30:00,000 --> 00:30:05,000 sequences. When did those seven ancestors live, 453 00:30:05,000 --> 00:30:10,000 well we don't really know, probably between 10-15,000 years ago. 454 00:30:10,000 --> 00:30:15,000 But, the western-European population descends from an 455 00:30:15,000 --> 00:30:20,000 stunningly small number of founders. 456 00:30:20,000 --> 00:30:22,000 Now clearly, DNA sequencing is terrific, but it's not good enough 457 00:30:22,000 --> 00:30:25,000 to know the names of those women, so I can tell you that they were not 458 00:30:25,000 --> 00:30:27,000 named Velda and Jasmine. [LAUGHTER] Anyhow, but here you 459 00:30:27,000 --> 00:30:30,000 can see, here you can, now obviously, these women in turn 460 00:30:30,000 --> 00:30:32,000 were related to one another, you can ask, you can do another kind 461 00:30:32,000 --> 00:30:35,000 of question. How much are all of our mitochondrial DNA are related to 462 00:30:35,000 --> 00:30:37,000 one another, how distantly related are they to one another, 463 00:30:37,000 --> 00:30:40,000 given the rate of evolution of mitochondrial DNA sequences? 464 00:30:40,000 --> 00:30:45,000 And if you ask that question, the answer is that we all had a 465 00:30:45,000 --> 00:30:51,000 common ancestress who lived about 150,000 years ago. 466 00:30:51,000 --> 00:30:57,000 All of us trace our mitochondrial DNA to her. Does that mean that 467 00:30:57,000 --> 00:31:02,000 there was only one woman alive there, she's called, Mitochondrial-Eve, 468 00:31:02,000 --> 00:31:08,000 again, we don't know her name. Does that mean there was only one woman 469 00:31:08,000 --> 00:31:14,000 alive, well it doesn't mean that at all because of what I just told you, 470 00:31:14,000 --> 00:31:20,000 in small populations the proto-human population. 471 00:31:20,000 --> 00:31:24,000 I just told you that certain polymorphisms die out because of 472 00:31:24,000 --> 00:31:28,000 this genetic drift, because of these stochastic events. 473 00:31:28,000 --> 00:31:32,000 And so, the founding human population could have had 20, 474 00:31:32,000 --> 00:31:36,000 50,100 individuals in it, but one woman's mitochondrial DNA happened 475 00:31:36,000 --> 00:31:41,000 because of these accidents to dominate, so that now, 476 00:31:41,000 --> 00:31:45,000 all of us have the same, are the descendents of her 477 00:31:45,000 --> 00:31:49,000 mitochondrial DNA. Clearly, in the intervening time 478 00:31:49,000 --> 00:31:53,000 since 150,000 years ago, accumulated mutations have, 479 00:31:53,000 --> 00:31:57,000 have altered subtly the mitochondrial DNA genome, 480 00:31:57,000 --> 00:32:02,000 so there's polymorphisms, And so one can make, 481 00:32:02,000 --> 00:32:08,000 one can drive phylogenies of different kinds of mitochondrial DNA, 482 00:32:08,000 --> 00:32:13,000 and look at the relatedness between different clades, 483 00:32:13,000 --> 00:32:19,000 different groups, of women in modern-day Europe. 484 00:32:19,000 --> 00:32:24,000 70% of Finish men, in Finland, have a y-chromosome 485 00:32:24,000 --> 00:32:30,000 polymorphism that is otherwise virtually unheard of in the rest of 486 00:32:30,000 --> 00:32:36,000 Europe. 70% of Finish men, now what does that mean? 487 00:32:36,000 --> 00:32:38,000 Well, to me to means that those 70% of Finish men descended from a 488 00:32:38,000 --> 00:32:41,000 common ancestor, a male who lived around, 489 00:32:41,000 --> 00:32:44,000 if you look at the sequences, who lived around two or three 490 00:32:44,000 --> 00:32:47,000 thousand years ago, and who, for some reason, 491 00:32:47,000 --> 00:32:50,000 became the ancestor of all the people living in modern Finland. 492 00:32:50,000 --> 00:32:52,000 That's extraordinary. There's four million people living in Finland 493 00:32:52,000 --> 00:32:55,000 today, and the males all have their inherit, inherit their y-chromosome 494 00:32:55,000 --> 00:32:58,000 from that man, we don't know exactly where he lived, 495 00:32:58,000 --> 00:33:01,000 But obviously the modern Finish 496 00:33:01,000 --> 00:33:05,000 population descends from a very small founder-group who came into 497 00:33:05,000 --> 00:33:09,000 what we call, modern Finland, relatively recently, maybe two-two 498 00:33:09,000 --> 00:33:13,000 and a half thousand years ago, and thereafter, did not freely 499 00:33:13,000 --> 00:33:16,000 interbreed with the rest of the European population. 500 00:33:16,000 --> 00:33:20,000 How do we know that? Because that y-chromosomal 501 00:33:20,000 --> 00:33:24,000 polymorphism is not present elsewhere, it's only present in 502 00:33:24,000 --> 00:33:28,000 Finland. So it was a genetic, and obviously linguistic, isolate. 503 00:33:28,000 --> 00:33:32,000 So where do we all come from, 504 00:33:32,000 --> 00:33:36,000 all of us human beings? How closely related are we to one another? 505 00:33:36,000 --> 00:33:40,000 Here's, here's a measurement of the distances between different 506 00:33:40,000 --> 00:33:44,000 mitochondrial DNA's from different branches of humanity. 507 00:33:44,000 --> 00:33:49,000 And what you see is something really quite extraordinary and 508 00:33:49,000 --> 00:33:53,000 stunning. Here, you'll see that the people, 509 00:33:53,000 --> 00:33:57,000 the non-African lineages here and here, are actually relatively 510 00:33:57,000 --> 00:34:01,000 closely related to one another. But if you look at the people who 511 00:34:01,000 --> 00:34:04,000 live in Africa, down here, there is enormous genetic 512 00:34:04,000 --> 00:34:08,000 diversity. Look how far these evolutionary branches reach back, 513 00:34:08,000 --> 00:34:11,000 look how long these are. The distance of these branches, 514 00:34:11,000 --> 00:34:14,000 of these roots, determines how far, how distantly related these 515 00:34:14,000 --> 00:34:18,000 individuals are, one to the other. 516 00:34:18,000 --> 00:34:21,000 And on the basis of that, and on the basis of a lot of other 517 00:34:21,000 --> 00:34:24,000 auxiliary genetic information, we can conclude that Africa was the 518 00:34:24,000 --> 00:34:28,000 site where genetic diversification was generated during 519 00:34:28,000 --> 00:34:31,000 human evolution. And that what happened, 520 00:34:31,000 --> 00:34:35,000 as a consequence of that diversification, 521 00:34:35,000 --> 00:34:39,000 is starting over the last 40, 50, 60,000 years ago, different 522 00:34:39,000 --> 00:34:42,000 populations, different sub-populations, 523 00:34:42,000 --> 00:34:46,000 small, isolated sub-populations, migrated out of Africa, took a very 524 00:34:46,000 --> 00:34:49,000 small sub-set of the polymorphisms with them, and became the 525 00:34:49,000 --> 00:34:53,000 founder-populations of a whole variety of whole different 526 00:34:53,000 --> 00:34:57,000 modern-day populations. These populations here are largely 527 00:34:57,000 --> 00:35:00,000 Mongoloid, these populations here are largely Caucasian, 528 00:35:00,000 --> 00:35:04,000 and here, we see that in Africa there's enormous genetic 529 00:35:04,000 --> 00:35:07,000 diversity. And by the way, 530 00:35:07,000 --> 00:35:11,000 all the genes that are present here, the alleles that are present here, 531 00:35:11,000 --> 00:35:15,000 can also be found in Africa, but in relatively small proportions 532 00:35:15,000 --> 00:35:19,000 in Africa. And we know this kind of diversity exists both for the 533 00:35:19,000 --> 00:35:23,000 mitochondrial DNA, and here's for the y-chromosomal DNA, 534 00:35:23,000 --> 00:35:26,000 again, we look for polymorphisms. And this is not a very good 535 00:35:26,000 --> 00:35:30,000 overhead, again, the reproduction was not very good, 536 00:35:30,000 --> 00:35:34,000 but what I'm showing you is that the evolutionary, the depth of these 537 00:35:34,000 --> 00:35:38,000 evolutionary branches is enormous in Africa, yet in other parts of the 538 00:35:38,000 --> 00:35:42,000 globe, people are much more closely-related to one another. 539 00:35:42,000 --> 00:35:45,000 Some people argue on the basis of the genetic-relatedness of western 540 00:35:45,000 --> 00:35:48,000 and northern Europeans, that the modern European population 541 00:35:48,000 --> 00:35:52,000 is largely descended from about 20 couples that moved into Europe about 542 00:35:52,000 --> 00:35:55,000 10,000 years ago, eight to ten thousand years ago, 543 00:35:55,000 --> 00:35:58,000 at the time when agriculture was introduced into Europe from the 544 00:35:58,000 --> 00:36:02,000 middle east, just on the basis of looking at these y-chromosomal 545 00:36:02,000 --> 00:36:06,000 sequences. And so, we human beings arose, 546 00:36:06,000 --> 00:36:11,000 even though we are reasonably distantly related to one another on 547 00:36:11,000 --> 00:36:16,000 this graph, keep in mind that we as a species, are enormously close to 548 00:36:16,000 --> 00:36:21,000 one another because of the youth of this, of our species. 549 00:36:21,000 --> 00:36:26,000 If you look at our, the time of this diversification was probably 550 00:36:26,000 --> 00:36:31,000 sometime between 80-100, 00 years ago, so how did it all 551 00:36:31,000 --> 00:36:36,000 happen? We can even figure out the history of humanity by beginning to 552 00:36:36,000 --> 00:36:42,000 look at these different kinds of polymorphisms. 553 00:36:42,000 --> 00:36:45,000 A long time ago, individuals went out from Africa, 554 00:36:45,000 --> 00:36:49,000 maybe starting 100,000 years ago, maybe starting more recently, 555 00:36:49,000 --> 00:36:53,000 and went across the southern rim of Eurasia, and we know already, 556 00:36:53,000 --> 00:36:56,000 we find archeological remains of Aborigines in Australia between 557 00:36:56,000 --> 00:37:00,000 40-60,000 years ago. And by the way, those people are 558 00:37:00,000 --> 00:37:04,000 very distantly related to the rest of us, having left and not 559 00:37:04,000 --> 00:37:08,000 intermingled with the rest of humanity for a very long 560 00:37:08,000 --> 00:37:11,000 period of time. There were Aborigines in Australia, 561 00:37:11,000 --> 00:37:15,000 already at a time when our ancestors, to the extent we had ancestors in 562 00:37:15,000 --> 00:37:19,000 Europe, were still battling the Neanderthals, who only died out 30, 563 00:37:19,000 --> 00:37:23,000 00 years ago. You may know by the way, you may have read in the 564 00:37:23,000 --> 00:37:27,000 newspaper, about a month ago, they discovered skeletons of very 565 00:37:27,000 --> 00:37:30,000 small people on an island Indonesia. In fact, those were probably not 566 00:37:30,000 --> 00:37:34,000 even homosapiens, those were probably a precursor 567 00:37:34,000 --> 00:37:38,000 species, because we know over the last two million years, 568 00:37:38,000 --> 00:37:42,000 there have been hominoids, look like human beings but are 569 00:37:42,000 --> 00:37:46,000 precursors, who might migrated out of Africa, who dispersed throughout 570 00:37:46,000 --> 00:37:50,000 Asia, and who eventually became extinct, 571 00:37:50,000 --> 00:37:53,000 So that the only modern human who exist are the descendents of this 572 00:37:53,000 --> 00:37:57,000 out migration that began about 100, 00 years ago. We know that about 15, 573 00:37:57,000 --> 00:38:00,000 00 years ago some of these people ended up going over here, 574 00:38:00,000 --> 00:38:04,000 to crossing in four different waves of migration, you can see it from 575 00:38:04,000 --> 00:38:08,000 the DNA, into the western hemisphere. 576 00:38:08,000 --> 00:38:12,000 Amerindians, that is, American Indians, Native Americans, 577 00:38:12,000 --> 00:38:16,000 are genetically rather homogenous. Why? Because they all descend from 578 00:38:16,000 --> 00:38:21,000 very small founder populations that came into the western hemisphere 579 00:38:21,000 --> 00:38:25,000 relatively recently. And there's enormous genetic 580 00:38:25,000 --> 00:38:30,000 homogeneity among different subgroups of individuals here in 581 00:38:30,000 --> 00:38:34,000 South America. Speaking of South America, 582 00:38:34,000 --> 00:38:39,000 if you look in some parts of Venezuela, what you find is that the 583 00:38:39,000 --> 00:38:43,000 mitochondrial DNA is largely of Indian-origin, 584 00:38:43,000 --> 00:38:48,000 but the y-chromosomal DNA is largely of European origin. 585 00:38:48,000 --> 00:38:52,000 So, what happens there, that's a testimonial to the tragic 586 00:38:52,000 --> 00:38:56,000 fate of the Indians, where the conquistadors from Spain 587 00:38:56,000 --> 00:39:00,000 came in, killed all the men, and took all the women, to be their 588 00:39:00,000 --> 00:39:04,000 brides. How else can you explain the fact that there's no Indian 589 00:39:04,000 --> 00:39:08,000 y-chromosomes, there's all, there is instead only 590 00:39:08,000 --> 00:39:12,000 European y-chromosomes. And here you can begin to see what 591 00:39:12,000 --> 00:39:16,000 happened here in New York, as well. 40,000 years ago people 592 00:39:16,000 --> 00:39:21,000 started trickling into Europe, and they hung around there for the 593 00:39:21,000 --> 00:39:26,000 next 30,000 years, pretty much on their own. 594 00:39:26,000 --> 00:39:30,000 The remnants of those people who came in, we know from DNA, 595 00:39:30,000 --> 00:39:35,000 are the Basques who live in northern Spain, who speak, 596 00:39:35,000 --> 00:39:40,000 by the way, a non-indo European language. 597 00:39:40,000 --> 00:39:43,000 They're the relics of this initial settlement by modern humans of 598 00:39:43,000 --> 00:39:47,000 Europe, starting 40, 00 years ago. And they had the 599 00:39:47,000 --> 00:39:50,000 continent for themselves for the next 30,000 years, 600 00:39:50,000 --> 00:39:54,000 until this new founder population came in, about 10, 601 00:39:54,000 --> 00:39:57,000 00 years ago. Here's the names of the girls who were in that group, 602 00:39:57,000 --> 00:40:01,000 Ursula and Katrine and Zenya, Tara, Jasmine, and Velda, and they became 603 00:40:01,000 --> 00:40:04,000 the modern agriculturalists, and swamped out the people who were 604 00:40:04,000 --> 00:40:08,000 there 40,000 years ago, who now only survive as a relic 605 00:40:08,000 --> 00:40:12,000 population. Here's a fun story I like to tell 606 00:40:12,000 --> 00:40:16,000 each year, and it's about the Cohen and y-chromosome, 607 00:40:16,000 --> 00:40:21,000 and you'll see what an amusing story this is, just from genetics. 608 00:40:21,000 --> 00:40:25,000 Now the name Cohen, in Hebrew means, a high priest, 609 00:40:25,000 --> 00:40:29,000 and you've heard people named Cohen, it's not such an uncommon name among 610 00:40:29,000 --> 00:40:34,000 the Jews. And it says, in the Bible, in Genesis and Exodus, 611 00:40:34,000 --> 00:40:38,000 that all the high priests in the Bible are the descendents of Aaron, 612 00:40:38,000 --> 00:40:43,000 the brother of Moses. And it's also been the practice for 613 00:40:43,000 --> 00:40:47,000 the last 3,000 years, that the only person who can become, 614 00:40:47,000 --> 00:40:51,000 the only male who can become a Cohen, is the son of a Cohen. 615 00:40:51,000 --> 00:40:56,000 In other words, you cannot be adopted into a family and acquire 616 00:40:56,000 --> 00:41:00,000 the name Cohen. And if that's all true, 617 00:41:00,000 --> 00:41:05,000 and if the Bible is true, and Aaron lived 3,000 years ago, 618 00:41:05,000 --> 00:41:09,000 whatever his name was, then it should be the case that all male 619 00:41:09,000 --> 00:41:14,000 Cohen's should have the same y-chromosome, right? 620 00:41:14,000 --> 00:41:17,000 Because they all descend, their family name is Cohen, 621 00:41:17,000 --> 00:41:21,000 they could only get it from their father, they could only get their 622 00:41:21,000 --> 00:41:25,000 y-chromosome from their father, so they should all have the same 623 00:41:25,000 --> 00:41:29,000 y-chromosome. Of course, you say that can't really be the 624 00:41:29,000 --> 00:41:32,000 case, because we know in this country, in this country, 625 00:41:32,000 --> 00:41:36,000 between five and ten percent of people, on average, 626 00:41:36,000 --> 00:41:40,000 are sending Father's Day cards to the wrong person. 627 00:41:40,000 --> 00:41:44,000 What does that mean? Non-paternity. 628 00:41:44,000 --> 00:41:48,000 When you do genetic counseling of family these days, 629 00:41:48,000 --> 00:41:53,000 one of the strictures is, that you never tell the family if 630 00:41:53,000 --> 00:41:57,000 the children have genetic polymorphisms that don't match that 631 00:41:57,000 --> 00:42:02,000 of the person whom they think is their father. They don't look like 632 00:42:02,000 --> 00:42:06,000 their, the person whom they regard as father, but that's always assumed 633 00:42:06,000 --> 00:42:11,000 to be a role of the genetic dice. So, how is that relevant? Well, 634 00:42:11,000 --> 00:42:16,000 let's talk about this descent from Aaron, who lived 3,000 years ago. 635 00:42:16,000 --> 00:42:20,000 We're talking about the y-chromosome being passed from one generation to 636 00:42:20,000 --> 00:42:24,000 the next, just like the family name. So what happened, what would happen 637 00:42:24,000 --> 00:42:29,000 if sometime over the last 3, 00 years, Mrs. Cohen had a dalliance, 638 00:42:29,000 --> 00:42:33,000 had an affair, with a television repairman, 639 00:42:33,000 --> 00:42:37,000 or the milkman, or the mailman, and never told Mr. Cohen? The 640 00:42:37,000 --> 00:42:42,000 y-chromosome, which her son thought he was getting from Dad, 641 00:42:42,000 --> 00:42:46,000 wouldn't be coming from Dad, it'd be coming from this other, 642 00:42:46,000 --> 00:42:51,000 the milkman or the mailman, and it wouldn't be a Cohen-y chromosome 643 00:42:51,000 --> 00:42:55,000 unless, by chance, the mailman or the milkman also 644 00:42:55,000 --> 00:43:00,000 happened to be a Cohen, [LAUGHTER], it could happen. 645 00:43:00,000 --> 00:43:04,000 But the chances are, roughly speaking, Cohen's are only 646 00:43:04,000 --> 00:43:08,000 four percent of all Jews, so the chances are against that 647 00:43:08,000 --> 00:43:12,000 happening. OK, so they did this experiment, 648 00:43:12,000 --> 00:43:16,000 and this is really astounding experiment. They went, 649 00:43:16,000 --> 00:43:20,000 the story is they went to a beach in Tel Aviv, I don't know whether they 650 00:43:20,000 --> 00:43:24,000 actually did that or not, and they picked up, they picked up 651 00:43:24,000 --> 00:43:28,000 100 male Cohen's who were Ashkenazi , Ashkenazi means their ancestors came 652 00:43:28,000 --> 00:43:32,000 from central Europe, over here. And they picked up 100 Sefardi 653 00:43:32,000 --> 00:43:36,000 Cohen's, and the Sefardi Cohen's come from Spain, 654 00:43:36,000 --> 00:43:40,000 North Africa, Egypt, Yemen, Iraq, Iran, Uzbekistan, 655 00:43:40,000 --> 00:43:44,000 Central Asia. And the last time that the Iraqi Cohen's and the 656 00:43:44,000 --> 00:43:48,000 Ashkenazi Cohen's were interbreeding, were about 500 BC, 657 00:43:48,000 --> 00:43:52,000 at the time of the Babylonian XL, so they've been apart a long time. 658 00:43:52,000 --> 00:43:56,000 And they looked at their y-chromosomes, 659 00:43:56,000 --> 00:44:00,000 and what they found was that 70% of the y-chromosomes of these male 660 00:44:00,000 --> 00:44:04,000 Cohen's, 70% of the Cohen's shared the same y-chromosome. 661 00:44:04,000 --> 00:44:07,000 Well, the same y-chromosome was present only in 15% of non-Cohen, 662 00:44:07,000 --> 00:44:11,000 Israeli Jews. Now think about that for a second. 70% of these men had 663 00:44:11,000 --> 00:44:14,000 the same y-chromosome, of course they didn't know they had 664 00:44:14,000 --> 00:44:18,000 the same y-chromosome, all they knew was that they had the 665 00:44:18,000 --> 00:44:22,000 same family name. And what that means, 666 00:44:22,000 --> 00:44:25,000 inescapably, is that over a period of two or three thousand years, 667 00:44:25,000 --> 00:44:29,000 it was hard to trace with exactitude when the common male ancestor lived, 668 00:44:29,000 --> 00:44:32,000 over a period of two or three thousand years, 669 00:44:32,000 --> 00:44:36,000 somehow the milkman and the mailman stayed away from Mrs. 670 00:44:36,000 --> 00:44:40,000 Cohen, or Mrs. Cohen was unusually virtuous. 671 00:44:40,000 --> 00:44:43,000 Because keep in mind, any single affair with the milkman 672 00:44:43,000 --> 00:44:47,000 or the mailman, over 3,000 years, 673 00:44:47,000 --> 00:44:50,000 would've broke this chain of inheritance, any single incidence of 674 00:44:50,000 --> 00:44:54,000 non-paternity. It's a really astounding story, 675 00:44:54,000 --> 00:44:57,000 and it's hard, there can be no artifact to it, 676 00:44:57,000 --> 00:45:01,000 there's no bias in it, there's no other way to explain it. 677 00:45:01,000 --> 00:45:04,000 And you can begin to find similar stories of families in England, 678 00:45:04,000 --> 00:45:08,000 where males are tenth cousins of one another, they have the same family 679 00:45:08,000 --> 00:45:12,000 name, and they also have the same y-chromosome. 680 00:45:12,000 --> 00:45:17,000 The most amusing commentary on this stems from a tribe that lives in 681 00:45:17,000 --> 00:45:22,000 southern Africa, and these people are called, 682 00:45:22,000 --> 00:45:27,000 Lemba, L-e-m-b-a. And the, the myth of the Lemba is that they descend 683 00:45:27,000 --> 00:45:32,000 from Jews who came down from the north, Jewish traitors. 684 00:45:32,000 --> 00:45:37,000 So just for the hell of it, some geneticists went down and drew 685 00:45:37,000 --> 00:45:42,000 blood from the male Lembas, and there's four casts of Lembas, 686 00:45:42,000 --> 00:45:47,000 there's the ruling class, there's the warriors, there's the farmers, 687 00:45:47,000 --> 00:45:51,000 the merchants, I don't know. And what they found was that all 688 00:45:51,000 --> 00:45:55,000 members of the, almost all members of the ruling 689 00:45:55,000 --> 00:45:59,000 cast among the Lembas, had the same y-chromosome, 690 00:45:59,000 --> 00:46:02,000 and the y-chromosome had exactly the same polymorphisms of the Cohen 691 00:46:02,000 --> 00:46:06,000 y-chromosome. No one in the other, no males in the other three casts 692 00:46:06,000 --> 00:46:10,000 had, or very few, had otherwise this y-chromosomal 693 00:46:10,000 --> 00:46:14,000 polymorphism. Go figure, I don't know what's going on. 694 00:46:14,000 --> 00:46:17,000 Now did those people look Jewish? Well, they looked like everybody 695 00:46:17,000 --> 00:46:20,000 else around them, because if there was a Mr. 696 00:46:20,000 --> 00:46:23,000 Cohen who came down there, three or four hundred years ago, 697 00:46:23,000 --> 00:46:27,000 and married in, he obviously married one of the local population. 698 00:46:27,000 --> 00:46:30,000 And there were no other people around from, coming in from the 699 00:46:30,000 --> 00:46:33,000 north, to marry to, so that 99% of the males in this 700 00:46:33,000 --> 00:46:37,000 ruling cast, who have the Cohen y-chromosome, 99% of their genes 701 00:46:37,000 --> 00:46:40,000 come from the local population, the only thing they inherited from 702 00:46:40,000 --> 00:46:44,000 Mr. Cohen was the y-chromosome. Where else would they get their 703 00:46:44,000 --> 00:46:48,000 genes? There wasn't a massive migration from the middle east down 704 00:46:48,000 --> 00:46:52,000 to the Lemba tribes, probably just one man came down 705 00:46:52,000 --> 00:46:56,000 selling trinkets, or who-knows-what, 706 00:46:56,000 --> 00:47:00,000 television sets, or VCRs, sometime over the last three or four 707 00:47:00,000 --> 00:47:04,000 hundred years. And somehow, for reasons that we 708 00:47:04,000 --> 00:47:08,000 have no idea, he became the ancestor of this cast of people in this tribe 709 00:47:08,000 --> 00:47:12,000 in the middle of Africa. And so you have stories that you 710 00:47:12,000 --> 00:47:16,000 begin to pick up, which are stranger than fiction, 711 00:47:16,000 --> 00:47:20,000 some of the weirdest stories that you've ever heard of in your life. 712 00:47:20,000 --> 00:47:24,000 Imagine having 3,000 years of uninterrupted transmission from, 713 00:47:24,000 --> 00:47:28,000 without a single case of non-paternity. 714 00:47:28,000 --> 00:47:32,000 It didn't happen all the cases, because I didn't say 100% of the 715 00:47:32,000 --> 00:47:36,000 Cohen men had it, on 30% of the occasions, 716 00:47:36,000 --> 00:47:40,000 there must have been some snipping of this chain of transmission. 717 00:47:40,000 --> 00:47:52,000 And keep in mind that this chain of transmission happened over a period 718 00:47:52,000 --> 00:48:04,000 of enormous political and upheaval, over the last 3,000 years. The 719 00:48:04,000 --> 00:48:17,000 middle east, and Europe, and North Africa, have not been 720 00:48:17,000 --> 00:48:29,000 tranquil places over that period of time. Enormous population dispersal, 721 00:48:29,000 --> 00:48:42,000 and confusion, and displacement, 722 00:48:42,000 --> 00:48:54,000 and yet we now begin to look, by looking at the DNA, we can begin 723 00:48:54,000 --> 00:49:07,000 to see all kinds of really interesting things. 724 00:49:07,000 --> 00:49:11,000 Next, on Friday, Eric is going to talk with you, 725 00:49:11,000 --> 00:49:16,000 I believe, on Monday, as well. And Wednesday, we're going to talk about 726 00:49:16,000 --> 00:49:20,000 a related topic, which is, how do all, 727 00:49:20,000 --> 00:49:25,000 how do these human genetic differences have implications for 728 00:49:25,000 --> 00:49:29,000 the way we think about one another, and the way that we will develop? 729 00:49:29,000 --> 00:49:34,000 See you then, a week from today.