1 00:00:01 --> 00:00:04 So we're shifting gears today. We're going to talk about molecular 2 00:00:04 --> 00:00:08 evolution, i.e. how do we understand how species 3 00:00:08 --> 00:00:12 evolve, how do we understand a lot about ourselves, 4 00:00:12 --> 00:00:17 how human evolution is taking place over the last couple hundred 5 00:00:17 --> 00:00:21 thousand years. And traditionally, 6 00:00:21 --> 00:00:25 evolution has been the purview of people who study the morphology of 7 00:00:25 --> 00:00:29 organisms, and when I talk about morphology, obviously I'm talking 8 00:00:29 --> 00:00:34 about shape and form. And by comparing organisms, 9 00:00:34 --> 00:00:38 starting already 250 years ago, one began to develop hierarchies of 10 00:00:38 --> 00:00:43 how different organisms on the planet are related to one another. 11 00:00:43 --> 00:00:47 You've seen this, undoubtedly, in high school biology. 12 00:00:47 --> 00:00:51 This is the study of phylogeny, and phylogeny has traditionally been 13 00:00:51 --> 00:00:57 14 00:00:57 --> 00:01:00 figured out by comparing the phenotypes, the morphologies of 15 00:01:00 --> 00:01:03 adults, sometimes embryonic development, and on that basis, 16 00:01:03 --> 00:01:06 attempting to extrapolate back in evolutionary time, 17 00:01:06 --> 00:01:10 about the relatedness of different organisms, one to the other. 18 00:01:10 --> 00:01:14 And in so doing, one has been able to create, 19 00:01:14 --> 00:01:18 for example, family trees, here's something that Charles Darwin was 20 00:01:18 --> 00:01:22 already interested in, the various kinds of finches on the 21 00:01:22 --> 00:01:27 Galapagos Islands off Peru, in the Pacific. And here, one is 22 00:01:27 --> 00:01:31 beginning to organize different bird species on the basis of whether 23 00:01:31 --> 00:01:35 they're more closely or less closely related to one another, 24 00:01:35 --> 00:01:39 and to draw pedigrees, which, one imagines, describe how they 25 00:01:39 --> 00:01:44 evolved, one from the other. i.e., organisms which are very 26 00:01:44 --> 00:01:48 similar to one another must be more closely related evolutionarily, 27 00:01:48 --> 00:01:53 and conversely, those that appear very differently from one another, 28 00:01:53 --> 00:01:58 morphologically, must be far more distantly related to one another. 29 00:01:58 --> 00:02:02 In fact, these kinds of morphologic extrapolations can be very 30 00:02:02 --> 00:02:07 misleading. So here, for example, are two kinds of eyes. 31 00:02:07 --> 00:02:11 The top eye is a Drysophila eye 32 00:02:11 --> 00:02:14 which, to state the obvious, looks a lot different from our eyes, 33 00:02:14 --> 00:02:18 which is that the chordate eyes shown the bottom. 34 00:02:18 --> 00:02:21 Totally different. Our rods and cones face backwards, 35 00:02:21 --> 00:02:24 the Drysophila Arthropod eyes, the light sensors face forward. 36 00:02:24 --> 00:02:27 Everything is different. And on the basis of that, 37 00:02:27 --> 00:02:30 you would say that these two organisms are independent 38 00:02:30 --> 00:02:34 evolutionary inventions, that they've been invented on two 39 00:02:34 --> 00:02:37 occasions, and that they have no relatedness, one to the 40 00:02:37 --> 00:02:41 other, at all. But I will tell you an extraordinary 41 00:02:41 --> 00:02:45 experiment. You can take, there's a master gene that controls 42 00:02:45 --> 00:02:50 eye development in the fly, Drosophila. It's called eyeless, 43 00:02:50 --> 00:02:55 if you knock it out then the eye doesn't develop at all. 44 00:02:55 --> 00:02:59 And you can take out of the mouse, what is apparently a related gene 45 00:02:59 --> 00:03:04 called small eye, so the fly gene is called eyeless 46 00:03:04 --> 00:03:09 and the mouse gene is called small eye. And you can put the small-eyed 47 00:03:09 --> 00:03:13 gene into the Drosophila genome, in a fly that lacks the eyeless gene. 48 00:03:13 --> 00:03:18 So here we're talking about two 49 00:03:18 --> 00:03:22 different genes. The fly gene is called eyeless, 50 00:03:22 --> 00:03:26 the mammalian gene, at least in mouse, is called small eye. 51 00:03:26 --> 00:03:30 If you knock out this gene in the fly genome, and replace it with this 52 00:03:30 --> 00:03:34 gene, you get a perfectly normal Drosophila eye. 53 00:03:34 --> 00:03:38 It's extraordinary. Or you can do the following, 54 00:03:38 --> 00:03:42 you can arrange it so that the mouse small eye gene is expressed 55 00:03:42 --> 00:03:46 ectopically. When I say ectopically, 56 00:03:46 --> 00:03:51 I mean that it's expressed in the wrong place, at the wrong time. 57 00:03:51 --> 00:03:56 So you can do the following experiment. In a fly genome, 58 00:03:56 --> 00:04:00 you can arrange it so that the mouse small eye gene becomes expressed on 59 00:04:00 --> 00:04:05 one of the extremities of the fly, on one of the legs of the fly. And 60 00:04:05 --> 00:04:10 now, on one of the extremities of the fly, an ectopic eye will develop, 61 00:04:10 --> 00:04:15 looks just like a Drosophila eye, but it's development is programmed 62 00:04:15 --> 00:04:19 by the mouse small eye gene. What I'm telling you is that these 63 00:04:19 --> 00:04:23 two genes are totally interchangeable, 64 00:04:23 --> 00:04:27 that they are effectively indistinguishable from one another, 65 00:04:27 --> 00:04:31 functionally they have some sequence relatedness, but in terms of the way 66 00:04:31 --> 00:04:34 they program development, they are effectively equivalent. 67 00:04:34 --> 00:04:38 And what this means is that the progenitor of these two genes 68 00:04:38 --> 00:04:42 must've already existed at the time that the flies and we diverged, 69 00:04:42 --> 00:04:46 which six or seven-hundred million years ago, and in the intervening 70 00:04:46 --> 00:04:50 six or seven-hundred million years, these genes have been totally 71 00:04:50 --> 00:04:53 unchanged. i.e., once the gene was developed, 72 00:04:53 --> 00:04:57 evolution could not tinker with it, and begin to change it in different 73 00:04:57 --> 00:05:00 ways, ostensibly because such tinkering would render these genes 74 00:05:00 --> 00:05:04 dysfunctional, and thereby would inactivate them, 75 00:05:04 --> 00:05:08 thereby depriving the organism of a critical sensory organ. 76 00:05:08 --> 00:05:11 So here we have an example, a dramatic example, of how 77 00:05:11 --> 00:05:15 morphology misleads us. Here we have an example of where we 78 00:05:15 --> 00:05:18 would say these two eyes, the two eyes I've shown you here, 79 00:05:18 --> 00:05:22 are so different from one another that they must, 80 00:05:22 --> 00:05:26 by necessity, be independent evolutionary inventions. 81 00:05:26 --> 00:05:29 But in fact, genetics tells us, and these gene-swapping experiments, 82 00:05:29 --> 00:05:33 tell us that the two eyes descend from a common ancestral eye, 83 00:05:33 --> 00:05:37 a prototypical eye, whose precise morphology we can't discern anymore. 84 00:05:37 --> 00:05:41 And so we begin to realize that if we really want to understand 85 00:05:41 --> 00:05:44 evolution and we really want to understand phylogeny, 86 00:05:44 --> 00:05:48 phylogeny being how the species are related to one another, 87 00:05:48 --> 00:05:52 we have to the DNA, and we have to begin to look not at phenotype, 88 00:05:52 --> 00:05:56 but we have to look instead, at genotype. 89 00:05:56 --> 00:06:01 The Darwinian model is pretty much like this, the survival of the 90 00:06:01 --> 00:06:06 fittest. And when I say that, we imagine that we have here, a 91 00:06:06 --> 00:06:11 genetically heterogeneous group of organisms within a species, 92 00:06:11 --> 00:06:16 and this, this number of individuals in the species could be 100, 93 00:06:16 --> 00:06:22 it could be 1,000,000. This particular individual, 94 00:06:22 --> 00:06:27 by chance, acquires a mutation, or an advantageous allele, through 95 00:06:27 --> 00:06:32 some genetic alteration. This genotype renders this organism 96 00:06:32 --> 00:06:36 more fit, phenotypically, has a selective advantage and 97 00:06:36 --> 00:06:40 consequently, over extended periods of time, which may be thousands or 98 00:06:40 --> 00:06:44 even millions of years, the descendents of the organism 99 00:06:44 --> 00:06:48 bearing this allele now have advantage, have greater reproductive 100 00:06:48 --> 00:06:52 advantage, survival advantage, compared with the other individuals 101 00:06:52 --> 00:06:56 in the same species, and therefore, the representation of 102 00:06:56 --> 00:07:00 this mutant allele in the gene pool of the species becomes expanded. 103 00:07:00 --> 00:07:03 When I say gene pool, I'm talking bout the common shared 104 00:07:03 --> 00:07:07 set of genes within the species, such as within the human species. 105 00:07:07 --> 00:07:10 And so eventually, the descendents of this organism, 106 00:07:10 --> 00:07:14 or the descendants of an organism bearing this allele, 107 00:07:14 --> 00:07:17 now become overrepresented in the population, because they're more fit. 108 00:07:17 --> 00:07:21 And then there can be another succession, i. 109 00:07:21 --> 00:07:24 ., there could be other mutations occurring subsequently. 110 00:07:24 --> 00:07:28 Once again, favoring the selective outgrowth of an individual bearing 111 00:07:28 --> 00:07:31 this allele, or this allele. And in addition, 112 00:07:31 --> 00:07:35 there can be the process of what one calls, speciation. 113 00:07:35 --> 00:07:38 That is to say, that if some parts of the species live in one place, 114 00:07:38 --> 00:07:42 and other parts of the species live in another place, 115 00:07:42 --> 00:07:45 geographically, they may no longer interbreed, and as a consequence, 116 00:07:45 --> 00:07:49 and because of the fact they're under different selective pressures, 117 00:07:49 --> 00:07:52 they may begin to diverge from another if, evolutionary speaking, 118 00:07:52 --> 00:07:56 because they're no longer actively exchanging genes within one another. 119 00:07:56 --> 00:08:00 And, as a consequence, one can have new species arriving. 120 00:08:00 --> 00:08:03 And what one believes, this happens over slow, 121 00:08:03 --> 00:08:07 slowly over evolutionary time, but it does arise, and to the extent 122 00:08:07 --> 00:08:11 it does, one eventually ends up with organisms here and here, 123 00:08:11 --> 00:08:15 which can no longer effectively interbreed with one another. 124 00:08:15 --> 00:08:18 That is to say, they become genetically so different from one 125 00:08:18 --> 00:08:22 another, that any hybrids formed between them are, 126 00:08:22 --> 00:08:26 in fact, sterile, for one reason or another, if they're at all 127 00:08:26 --> 00:08:30 interested in breeding with one another to begin with. 128 00:08:30 --> 00:08:33 And what this means is that we can begin to trace how closely or 129 00:08:33 --> 00:08:37 distantly related species are to one another, simply by asking how 130 00:08:37 --> 00:08:40 closely or similarly related are their DNA sequences? 131 00:08:40 --> 00:08:44 If, distantly related organisms have very distantly related 132 00:08:44 --> 00:08:48 sequences, and closely related organisms must have sequences which 133 00:08:48 --> 00:08:51 are very similar to one another. And over evolutionary time, there's 134 00:08:51 --> 00:08:55 a so-called mutational clock, where one, where each species 135 00:08:55 --> 00:08:59 accumulates a certain number of point mutations, 136 00:08:59 --> 00:09:02 base substitutions in it's DNA, per million years, and the longer 137 00:09:02 --> 00:09:06 the two species are separated from one another, the greater will be the 138 00:09:06 --> 00:09:10 difference in their sequence diversity. 139 00:09:10 --> 00:09:14 And on that simple basis, one can begin to construct 140 00:09:14 --> 00:09:18 evolutionary trees of, for example, the entire cellular 141 00:09:18 --> 00:09:22 life on the planet. And here's such an evolutionary 142 00:09:22 --> 00:09:27 tree, where what's being compared is the ribosomal RNA sequences, 143 00:09:27 --> 00:09:31 i.e., the small ribosomal RNA. Remember, ribosomes have two 144 00:09:31 --> 00:09:35 subunits, small and large, in the case of prokaryotes, 145 00:09:35 --> 00:09:39 it's 16S RNA, that is, it's sedimentation rate. 146 00:09:39 --> 00:09:43 In the case of mammals, it's 18S. In both cases, 147 00:09:43 --> 00:09:47 these are small ribosomal RNA subunits. The ribosome was only 148 00:09:47 --> 00:09:51 invented on one occasion during the evolution of life on the planet, 149 00:09:51 --> 00:09:55 so one can begin to compare since all cellular life forms have life 150 00:09:55 --> 00:09:58 forms, one can ask how similar, or dissimilar, are the various 151 00:09:58 --> 00:10:02 sequences and coding, in small ribosomal RNA subunits? 152 00:10:02 --> 00:10:06 And on the basis of that, one has concluded that there are actually 153 00:10:06 --> 00:10:10 three branches of cellular life on the planet. 154 00:10:10 --> 00:10:13 The bacteria indicated here, this is not such a great Xerox, 155 00:10:13 --> 00:10:17 where you see a whole series of different kinds of bacteria, 156 00:10:17 --> 00:10:20 indicated on this tree. Sorry about the poor reproduction. 157 00:10:20 --> 00:10:24 Here there's a dashed line indicating that we're talking, 158 00:10:24 --> 00:10:28 there's a second kingdom in the middle here, indicated by what are 159 00:10:28 --> 00:10:31 called archae, and the archae are also, 160 00:10:31 --> 00:10:35 from our point of view, prokaryotes, but they're not bacteria. They are 161 00:10:35 --> 00:10:39 a single-cell life form, they're often found in unusual 162 00:10:39 --> 00:10:42 situations, for instance, in thermal vents in the bottom of 163 00:10:42 --> 00:10:46 the ocean floor, some of them are able to stand high 164 00:10:46 --> 00:10:50 salt, some of them are able to stand high temperature, 165 00:10:50 --> 00:10:54 like therma fillus, therma proteus, and so fourth. 166 00:10:54 --> 00:10:58 And these, their ribosomal RNAs, are so different from those of 167 00:10:58 --> 00:11:02 bacteria, that they've been placed in their own separate kingdom. 168 00:11:02 --> 00:11:06 And finally, here are the eukaryotes, all over here. 169 00:11:06 --> 00:11:10 These are all eukaryotic cells, starting here. And we, our cells, 170 00:11:10 --> 00:11:14 seem to be slightly more closely related to those of the Archaea, 171 00:11:14 --> 00:11:18 if you follow this ribosomal sequences, than they are to 172 00:11:18 --> 00:11:22 the actual bacteria. So, there's actually two major 173 00:11:22 --> 00:11:26 prokaryotic life forms on the planet. The first living organism, 174 00:11:26 --> 00:11:30 well if you begin to try to look back in geological record, 175 00:11:30 --> 00:11:34 it looks like the first living cellular life forms existed already 176 00:11:34 --> 00:11:38 3-3.5 billion years ago, not so long after the planet was 177 00:11:38 --> 00:11:42 formed, which was between 4. and 4.5 billion years ago. And 178 00:11:42 --> 00:11:46 here's the whole eukaryotic tree, and if we look at the eukaryotic 179 00:11:46 --> 00:11:50 trees, remembering here that we're starting at 3.5 billion years ago, 180 00:11:50 --> 00:11:53 And we're using this evolutionary clock to determine relatedness, 181 00:11:53 --> 00:11:56 then we see a whole series of single-cell eukaryotes, 182 00:11:56 --> 00:12:00 here are their names are, these are protozoan, eukaryotic 183 00:12:00 --> 00:12:03 protozoan. Here's Amoeba, here are slime molds, here are 184 00:12:03 --> 00:12:07 cilliates, we're still at single-cell organisms. 185 00:12:07 --> 00:12:10 Finally we get to multi-cellular organisms, plants, 186 00:12:10 --> 00:12:14 fungi, and animals, and so, all animals on the planet 187 00:12:14 --> 00:12:17 are a relatively recent invention. All animals, all of the metazoan, 188 00:12:17 --> 00:12:21 are just on this very small branch, and we know that this very small 189 00:12:21 --> 00:12:25 branch started around 600-650 million years ago, 190 00:12:25 --> 00:12:29 maybe 700 million years ago. And that was the time, roughly 191 00:12:29 --> 00:12:32 speaking, when we and flies last had our common ancestor, 192 00:12:32 --> 00:12:36 otherwise, to state the obvious, we and flies are very different. 193 00:12:36 --> 00:12:40 The fact that the gene for encoding the eye has been conserved, 194 00:12:40 --> 00:12:44 so faithfully, over enormous evolutionary period of time 195 00:12:44 --> 00:12:48 indicates something else, And that is, certain genes can 196 00:12:48 --> 00:12:52 evolve progressively over a long period of time, 197 00:12:52 --> 00:12:57 because they don't encode vital functions, or they may even be 198 00:12:57 --> 00:13:02 sequences between genes that don't encode phenotype at all. 199 00:13:02 --> 00:13:06 Imagine, for example, we have a situation were here we have a gene 200 00:13:06 --> 00:13:11 which encodes a vital function, like the eye, here's another gene 201 00:13:11 --> 00:13:16 that encodes another function, oh I don't know, a leg. 202 00:13:16 --> 00:13:19 And here we have intergenic sequences. After all, 203 00:13:19 --> 00:13:23 as you have learned by now, more than 96% of the DNA in our 204 00:13:23 --> 00:13:27 genome, doesn't encode proteins, and probably isn't even responsible 205 00:13:27 --> 00:13:31 for regulating genes. So these sequences, right in here, 206 00:13:31 --> 00:13:34 can mutate freely during the course of evolution, without having a 207 00:13:34 --> 00:13:38 deleterious effect on the phenotype of the organism. 208 00:13:38 --> 00:13:42 There's no evolutionary pressure to constrain the evolution of these 209 00:13:42 --> 00:13:46 genes, but if this gene over here encodes an eyes, 210 00:13:46 --> 00:13:49 And if this gene has been optimized in it's sequence, 211 00:13:49 --> 00:13:53 early in the course of evolution, that any subsequently occurring 212 00:13:53 --> 00:13:57 mutations will compromise it's function, and therefore there's 213 00:13:57 --> 00:14:00 enormous selective pressure to eliminate any organism which has 214 00:14:00 --> 00:14:04 begun to tinker with the sequence of this gene, by changing it's sequence. 215 00:14:04 --> 00:14:08 Here, in stark contrast, there's no such selective pressure. 216 00:14:08 --> 00:14:11 The organism, that is, 217 00:14:11 --> 00:14:14 can tinker at will with this. I don't mean literally that the 218 00:14:14 --> 00:14:18 organism is able to tinker with it's own DNA sequences, 219 00:14:18 --> 00:14:21 but the hand of evolution can change these sequences in here, 220 00:14:21 --> 00:14:24 at will, without having any effect on the viability of the organism on 221 00:14:24 --> 00:14:27 it's selective, or Darwinian, fitness, 222 00:14:27 --> 00:14:30 and therefore, such mutations in these, in these sequences, 223 00:14:30 --> 00:14:34 are neutral mutation, they have on effect on phenotype, 224 00:14:34 --> 00:14:37 and they will not be eliminated from the gene pool. 225 00:14:37 --> 00:14:40 Again here, mutations in these vital, critical genes will be 226 00:14:40 --> 00:14:43 eliminated from the gene pool. So that's another one of the 227 00:14:43 --> 00:14:46 principles in molecular evolution that we want to talk about. 228 00:14:46 --> 00:14:50 And if you follow these principles, we can not only do, draw 229 00:14:50 --> 00:14:53 evolutionary trees like this, which have a grand scope, a scale of 230 00:14:53 --> 00:14:56 three and a half billion years, we can talk, for example, about how 231 00:14:56 --> 00:15:00 different kinds of bears are related to one another, 232 00:15:00 --> 00:15:03 and on the basis, once again, of their DNA sequence. 233 00:15:03 --> 00:15:06 Or, if you want, we can even look at how different kinds of 234 00:15:06 --> 00:15:10 domesticated animals are related to one another. 235 00:15:10 --> 00:15:14 This is kind of a fun undertaking. Look at this. Why is it fun? Well 236 00:15:14 --> 00:15:19 it's, it's kind of an amusing idea, how often were cows domesticated 237 00:15:19 --> 00:15:23 during the history of humanity? How often were sheep domesticated? 238 00:15:23 --> 00:15:28 Pigs, water buffalos, and horses. And what you see here is that cattle 239 00:15:28 --> 00:15:32 were domesticated on two occasions, probably once in Western Asia, the 240 00:15:32 --> 00:15:37 middle east, and once in Eastern Asia. Sheep were domesticated twice, 241 00:15:37 --> 00:15:42 all modern sheep following these two families here. 242 00:15:42 --> 00:15:46 Obviously they share a common ancestor someway back, 243 00:15:46 --> 00:15:50 but most sheep either fall here or here. Pigs seem to have been 244 00:15:50 --> 00:15:54 domesticated twice, once over here and once over here, 245 00:15:54 --> 00:15:58 water buffalos twice, horses are very confusing, 246 00:15:58 --> 00:16:02 it looks like they were domesticated on several occasions because they're 247 00:16:02 --> 00:16:06 all over the map, they're not two clusters of 248 00:16:06 --> 00:16:10 closely-related varieties, like here and here. What others, 249 00:16:10 --> 00:16:14 dogs, that's recently, I forget what the number is for dogs, once. 250 00:16:14 --> 00:16:18 Dogs were domesticated once, probably the earliest domestication, 251 00:16:18 --> 00:16:22 about 100,000 years ago. They all have one common radiating tree, 252 00:16:22 --> 00:16:26 here we have two radiating trees, one cluster over here, one cluster 253 00:16:26 --> 00:16:31 over here, with sheep, pigs, and so fourth. So we can even, 254 00:16:31 --> 00:16:35 so you can learn an enormous amount about even the history of 255 00:16:35 --> 00:16:40 agriculture, by looking at these kinds of DNA pedigree. 256 00:16:40 --> 00:16:44 Here's some other interesting principles. Mitochondrial DNA 257 00:16:44 --> 00:16:49 passes always from the mother, so when a fertilized egg is formed, 258 00:16:49 --> 00:16:53 Dad gives his chromosomes, but he doesn't donate for any, 259 00:16:53 --> 00:16:58 doesn't donate any mitochondrial DNA. I remember visiting a friend in 260 00:16:58 --> 00:17:03 North Carolina in 1974, and he was looking at the 261 00:17:03 --> 00:17:07 mitochondrial DNA of mules and, when you breed a horse and a donkey, 262 00:17:07 --> 00:17:12 what do you get out? You get a mule out, 263 00:17:12 --> 00:17:18 or, what happens if you do it the other way? What happens if the 264 00:17:18 --> 00:17:24 father is a horse, and the mother is a donkey? 265 00:17:24 --> 00:17:30 It's a hinny, it's actually called a hinny. So there's two ways of 266 00:17:30 --> 00:17:36 breeding, and the question is now, and by the way, it's not so nice to 267 00:17:36 --> 00:17:42 have a father being the horse and the mother being the mule. 268 00:17:42 --> 00:17:45 Why? Because Mom isn't used to carrying an embryo that's much 269 00:17:45 --> 00:17:49 larger than she's adapted to. The other way is fine, because then 270 00:17:49 --> 00:17:53 she can carry a small embryo, but if Dad comes from a much larger 271 00:17:53 --> 00:17:57 species, then the fetus that the female donkey must carry, 272 00:17:57 --> 00:18:00 is larger than her womb is really evolved to carry. 273 00:18:00 --> 00:18:04 So, you don't often see these hinnies around because they cause 274 00:18:04 --> 00:18:08 great difficulty at birth. In any case, why did I get into 275 00:18:08 --> 00:18:12 this digression? Glad I asked that. 276 00:18:12 --> 00:18:15 The question was, where did the mitochondrial DNA come? 277 00:18:15 --> 00:18:19 1974, this was still a hot question. And it turned out, 278 00:18:19 --> 00:18:22 the mitochondrial DNA in both the mules and the hinnies came always 279 00:18:22 --> 00:18:26 from Mom. There was not a trace of mitochondrial DNA from the father 280 00:18:26 --> 00:18:29 and, as a consequence, this begins to cause us to realize 281 00:18:29 --> 00:18:33 where our mitochondrial DNA comes from. So his mitochondrial DNA 282 00:18:33 --> 00:18:36 comes from his mother, his maternal grandmother, 283 00:18:36 --> 00:18:40 her mother, her mother before her, and so fourth, and the same for each 284 00:18:40 --> 00:18:43 one of you. And what this means is that if you 285 00:18:43 --> 00:18:47 look at a pedigree like this, and for example, here we have a 286 00:18:47 --> 00:18:50 mother and a father, girls are always round, 287 00:18:50 --> 00:18:54 boys are square. And here you'll see the mitochondrial DNA, 288 00:18:54 --> 00:18:57 it's donated to all of the children, but the fact is that these boys, 289 00:18:57 --> 00:19:01 when they mate, when they have offspring, 290 00:19:01 --> 00:19:05 they will no longer pass along her mitochondrial DNA, 291 00:19:05 --> 00:19:08 so it will be lost. And the only way the mitochondrial 292 00:19:08 --> 00:19:12 DNA can be transmitted is through one of her daughters, 293 00:19:12 --> 00:19:16 who in turn, have daughters. Here you see the situation where 294 00:19:16 --> 00:19:20 almost all of her mitochondrial DNA is lost, except for this female 295 00:19:20 --> 00:19:24 descendent who, once again, passes it on to her sons 296 00:19:24 --> 00:19:28 and daughters. Only the daughters, 297 00:19:28 --> 00:19:33 again, can transmit mitochondrial DNA. And there is equity in life, 298 00:19:33 --> 00:19:37 it doesn't often happen. Jack Kennedy said life is unfair, 299 00:19:37 --> 00:19:41 but sometimes it's reasonably fair, but here is the y-chromosomes, the 300 00:19:41 --> 00:19:46 y-counterpart. Keep in mind, the y-chromosome only 301 00:19:46 --> 00:19:50 passes from father-to-son, to father-to-son, and exactly the 302 00:19:50 --> 00:19:54 same dynamics apply. And importantly, this is critical 303 00:19:54 --> 00:19:58 for our thinking now, neither the y-chromosome nor the 304 00:19:58 --> 00:20:02 mitochondrial DNA recombines with another chromosome. 305 00:20:02 --> 00:20:06 And therefore, the complexities of diploid mendelian genetics are 306 00:20:06 --> 00:20:10 obviated. So when you're looking at, for example, the mitochondrial DNA, 307 00:20:10 --> 00:20:14 you can look at the pure results of accumulated mutations, 308 00:20:14 --> 00:20:17 You don't have to worry about crossing-over, 309 00:20:17 --> 00:20:21 you don't have to worry about exchange of portions of a gene 310 00:20:21 --> 00:20:25 between two homologous chromosomes. It doesn't happen with the 311 00:20:25 --> 00:20:29 y-chromosome because there's only one of them in the cell, 312 00:20:29 --> 00:20:33 and it doesn't happen with the mitochondrial DNA because there's no 313 00:20:33 --> 00:20:37 other DNA for it to equilibrate with. As a consequence, 314 00:20:37 --> 00:20:41 we can begin to think about what happens with mitochondrial DNA and 315 00:20:41 --> 00:20:45 y-chromosomal DNA, in young and old species. 316 00:20:45 --> 00:20:48 So let's talk about a recently formed species, 317 00:20:48 --> 00:20:52 and let's say we have a young species down here, 318 00:20:52 --> 00:20:55 below the illustration, and now this species, which has 319 00:20:55 --> 00:20:59 recently come into existence for whatever reason, 320 00:20:59 --> 00:21:02 hangs around for the next couple million years. 321 00:21:02 --> 00:21:06 And while it hangs around, there will be random mutations, 322 00:21:06 --> 00:21:10 which strike the genomes of individual members of that species. 323 00:21:10 --> 00:21:14 And therefore, the longer the life of the species 324 00:21:14 --> 00:21:18 as a whole, the more genetically diverse will become the individuals 325 00:21:18 --> 00:21:22 in the species, and therefore, this species will 326 00:21:22 --> 00:21:26 grow to have more and more genetic diversity, just because of the 327 00:21:26 --> 00:21:30 random stochastic mutations that accumulate in different peoples 328 00:21:30 --> 00:21:34 genomes in the course of the life of this species, over millions of years. 329 00:21:34 --> 00:21:38 Again, keep in mind that the vast majority of these accumulated 330 00:21:38 --> 00:21:42 mutations will be mutual mutations, which will not affect phenotype, and 331 00:21:42 --> 00:21:46 therefore, they will not be eliminated by Darwinian selection. 332 00:21:46 --> 00:21:50 And many of these neutral mutations, which have no effect on organismic 333 00:21:50 --> 00:21:54 fitness, but are simply evolutionary neutral, are sometimes called 334 00:21:54 --> 00:21:59 polymorphisms. The term polymorphism, 335 00:21:59 --> 00:22:03 -morph is once again morphology, derives from the fact that species 336 00:22:03 --> 00:22:07 tend to be polymorphic, we don't all have blond hair, 337 00:22:07 --> 00:22:11 we don't all have brown eyes. We, as a species, 338 00:22:11 --> 00:22:15 have a great variability in phenotype, we're polymorphic, 339 00:22:15 --> 00:22:18 and yet having black hair, and having blond hair, 340 00:22:18 --> 00:22:22 and having red hair, none of those is considered mutant, 341 00:22:22 --> 00:22:25 none of those is considered pathological. I. 342 00:22:25 --> 00:22:29 ., among the group of normal phenotypes, there's a whole series 343 00:22:29 --> 00:22:32 of different gradations, and these are considered normal 344 00:22:32 --> 00:22:36 gradations in phenotype, but at the genetic level, 345 00:22:36 --> 00:22:40 we talk about polymorphisms in the same sense. 346 00:22:40 --> 00:22:43 Genetically distinct nucleotide sequences, which again, 347 00:22:43 --> 00:22:47 are not pathological, they don't create a disadvantageous phenotype. 348 00:22:47 --> 00:22:51 And as a consequence, they are once again, not selected against. 349 00:22:51 --> 00:22:54 Now look what happens over here. Here we have great genetic 350 00:22:54 --> 00:22:58 diversity, but what will happen is, for one reason or another, only a 351 00:22:58 --> 00:23:02 small subset of individuals constituting this species, 352 00:23:02 --> 00:23:06 will turn out to be the ancestors of the successor species. 353 00:23:06 --> 00:23:09 Here's the next species that arises. And why will these just be the 354 00:23:09 --> 00:23:13 ancestors? Well, everybody else could get killed off 355 00:23:13 --> 00:23:16 through some plague, they might get killed off by 356 00:23:16 --> 00:23:20 somebody going out and purposefully killing them, or, 357 00:23:20 --> 00:23:23 it might just be that a meteor comes down and wipes all these guys out, 358 00:23:23 --> 00:23:27 and these are the only ones in here, from this small subset of the 359 00:23:27 --> 00:23:31 original species, who end up surviving, 360 00:23:31 --> 00:23:34 and who end up becoming the precursors, the ancestors, 361 00:23:34 --> 00:23:38 of the new species, and once again, undergoes a period of 362 00:23:38 --> 00:23:42 diversification. And what we have therefore, 363 00:23:42 --> 00:23:46 is a diversification and then a collapse of genetic diversity. 364 00:23:46 --> 00:23:50 Here, this species, because it came from a small group, 365 00:23:50 --> 00:23:54 is initially rather, rather homogenous genetically, 366 00:23:54 --> 00:23:59 but with the passage of evolutionary time, once again, 367 00:23:59 --> 00:24:03 there's evolutionary diversification. So, an older species actually ends 368 00:24:03 --> 00:24:07 up being much more genetically diverse than does the 369 00:24:07 --> 00:24:12 younger species. If you look at two chimpanzees 370 00:24:12 --> 00:24:16 living on opposite sides of the same hill in West Africa, 371 00:24:16 --> 00:24:20 they are genetically far more distantly related to one another, 372 00:24:20 --> 00:24:24 than any one of us, by a factor of 10 to 15. Two chimpanzees, 373 00:24:24 --> 00:24:28 they look exactly the same, they have the same peculiar habits, 374 00:24:28 --> 00:24:32 but they're genetically far more distantly-related than we are to 375 00:24:32 --> 00:24:36 one-another, than I am to any one of you, or than any one of you is to 376 00:24:36 --> 00:24:40 one another. And what does that mean? 377 00:24:40 --> 00:24:45 It means that, roughly speaking, 378 00:24:45 --> 00:24:50 the species of chimpanzees is, at least, 10 or 15 times older than 379 00:24:50 --> 00:24:56 our species are. We're a young species, 380 00:24:56 --> 00:25:01 chimpanzees probably first speciated three or four million years ago, 381 00:25:01 --> 00:25:07 if the paleontological record is, is accurate. Paleontology is the 382 00:25:07 --> 00:25:12 study of old, dusty bones, so you can begin to imagine when 383 00:25:12 --> 00:25:18 chimpanzee bones become recognizable in the earth. 384 00:25:18 --> 00:25:22 So a paleontologist says that, that chimps aren't that old, and it 385 00:25:22 --> 00:25:27 begins to suggest that our species is only about 200, 386 00:25:27 --> 00:25:32 00 years old, at the oldest. Now you say 200,000 years is a long 387 00:25:32 --> 00:25:36 time, but it isn't so long because I started out this discussion talking 388 00:25:36 --> 00:25:41 about 3.5 billion years, 3.5 times ten to the ninth, 389 00:25:41 --> 00:25:46 and now I'm talking about two times ten to the fourth. 390 00:25:46 --> 00:25:51 Is that right? No, two times ten to the fifth. 391 00:25:51 --> 00:25:55 Four orders of magnitude difference. So that means that our species, we 392 00:25:55 --> 00:25:59 went through a bottleneck about 200-250,000 years ago, 393 00:25:59 --> 00:26:04 and because that is so recent, we haven't had a chance to actually 394 00:26:04 --> 00:26:08 acquire much genetic diversity. We're actually very closely related 395 00:26:08 --> 00:26:12 to one another, although to talk to people, 396 00:26:12 --> 00:26:17 you'd think we were all very distantly related to one another. 397 00:26:17 --> 00:26:21 Here's another interesting notion, which also figures in, and that is, 398 00:26:21 --> 00:26:26 what happens in the genetics of small populations? 399 00:26:26 --> 00:26:30 So here we started out with eight individuals, and let's assume for a 400 00:26:30 --> 00:26:34 moment, that this population has a steady size, i. 401 00:26:34 --> 00:26:38 . it doesn't increase or decrease over the course of several 402 00:26:38 --> 00:26:42 generations. And what that means is that each couple will, 403 00:26:42 --> 00:26:46 on average, leave behind two children, and those two children 404 00:26:46 --> 00:26:50 will breed, and each of them will, couples in the successor population, 405 00:26:50 --> 00:26:54 will leave behind two children. And what you see already, 406 00:26:54 --> 00:26:58 in such small populations, is that for example, this male here 407 00:26:58 --> 00:27:02 has two girls, and right away, 408 00:27:02 --> 00:27:06 to the extent he had an interesting y-chromosome, that y-chromosome was 409 00:27:06 --> 00:27:10 lost from the gene pool. This girl, here, had an interesting 410 00:27:10 --> 00:27:14 mitochondrial DNA, but right away that's lost, 411 00:27:14 --> 00:27:18 because she has, she has just two boys. And what you see, 412 00:27:18 --> 00:27:22 in very rapid order, in small populations, there's a 413 00:27:22 --> 00:27:26 homogenization of the genetic compliment, just because the alleles 414 00:27:26 --> 00:27:30 are lost within what's called, genetic drift. 415 00:27:30 --> 00:27:34 And as a consequence, very rapidly, there becomes 416 00:27:34 --> 00:27:38 homozygosity at many loci in very small populations. 417 00:27:38 --> 00:27:42 A real-life situation comes from Mutiny on the Bounty, 418 00:27:42 --> 00:27:46 where Fletcher Christian ends up getting shipwrecked on, 419 00:27:46 --> 00:27:50 what island was it, Pitcairn Island, which is somewhere on the South 420 00:27:50 --> 00:27:54 Pacific, South Atlantic, I forget where. Anyhow, today if 421 00:27:54 --> 00:27:58 you go to Pitcairn Island, almost everybody is called, 422 00:27:58 --> 00:28:02 almost everybody has a family name, Christian. 423 00:28:02 --> 00:28:05 Why? Was it that he was more studly and fecund than everybody else? 424 00:28:05 --> 00:28:08 Probably not. What probably happened was, in the same dynamics 425 00:28:08 --> 00:28:12 that dictates the homogenization of y-chromosomes, 426 00:28:12 --> 00:28:15 dictates the homogenization of family names. So, 427 00:28:15 --> 00:28:18 if you isolate people in a small demographic isolate, 428 00:28:18 --> 00:28:22 like an island in the middle of the ocean, over a period of generations, 429 00:28:22 --> 00:28:25 roughly equal to, I think, twice the number of individuals in the steady, 430 00:28:25 --> 00:28:28 state population, everybody will have the same family name, 431 00:28:28 --> 00:28:32 because the other family names will, by chance, in a small population, 432 00:28:32 --> 00:28:36 just be lost. On my father's side of the family, 433 00:28:36 --> 00:28:40 I have hundreds of cousins with my family name, and on my mother's side 434 00:28:40 --> 00:28:44 of the family, not a single one, 435 00:28:44 --> 00:28:48 just as an example of this kind of trait. Now keep in mind that this 436 00:28:48 --> 00:28:52 evolutionary diversification can also affect the y-chromosome, 437 00:28:52 --> 00:28:56 so therefore, there are different y-chromosomes across the face of the 438 00:28:56 --> 00:29:00 planet, which can be distinguished, not because they're better or lesser 439 00:29:00 --> 00:29:04 y-chromosomes, in terms of the phenotype of 440 00:29:04 --> 00:29:08 maleness, but because they've accumulated polymorphisms 441 00:29:08 --> 00:29:12 over a period of time. They may be single-nucleotide 442 00:29:12 --> 00:29:16 polymorphisms, but these single-nucleotide 443 00:29:16 --> 00:29:20 polymorphisms can be used to determine how closely, 444 00:29:20 --> 00:29:24 or distantly related, are individuals to one another. 445 00:29:24 --> 00:29:28 Let's look at the mitochondrial DNA of women in western Europe, 446 00:29:28 --> 00:29:33 and if you look at the mitochondrial DNA of women in western Europe, 447 00:29:33 --> 00:29:37 you find that they only have, how many different things there? 448 00:29:37 --> 00:29:41 One, two, three, four, five, six, seven, there's seven basic 449 00:29:41 --> 00:29:45 types of mitochondrial DNA that are found in western and northern 450 00:29:45 --> 00:29:50 European women. And what that means is, 451 00:29:50 --> 00:29:55 inescapably, people who live in modern-day Europe, 452 00:29:55 --> 00:30:00 descend from seven women who had these respective mitochondrial DNA 453 00:30:00 --> 00:30:05 sequences. When did those seven ancestors live, 454 00:30:05 --> 00:30:10 well we don't really know, probably between 10-15,000 years ago. 455 00:30:10 --> 00:30:15 But, the western-European population descends from an 456 00:30:15 --> 00:30:20 stunningly small number of founders. 457 00:30:20 --> 00:30:22 Now clearly, DNA sequencing is terrific, but it's not good enough 458 00:30:22 --> 00:30:25 to know the names of those women, so I can tell you that they were not 459 00:30:25 --> 00:30:27 named Velda and Jasmine. [LAUGHTER] Anyhow, but here you 460 00:30:27 --> 00:30:30 can see, here you can, now obviously, these women in turn 461 00:30:30 --> 00:30:32 were related to one another, you can ask, you can do another kind 462 00:30:32 --> 00:30:35 of question. How much are all of our mitochondrial DNA are related to 463 00:30:35 --> 00:30:37 one another, how distantly related are they to one another, 464 00:30:37 --> 00:30:40 given the rate of evolution of mitochondrial DNA sequences? 465 00:30:40 --> 00:30:45 And if you ask that question, the answer is that we all had a 466 00:30:45 --> 00:30:51 common ancestress who lived about 150,000 years ago. 467 00:30:51 --> 00:30:57 All of us trace our mitochondrial DNA to her. Does that mean that 468 00:30:57 --> 00:31:02 there was only one woman alive there, she's called, Mitochondrial-Eve, 469 00:31:02 --> 00:31:08 again, we don't know her name. Does that mean there was only one woman 470 00:31:08 --> 00:31:14 alive, well it doesn't mean that at all because of what I just told you, 471 00:31:14 --> 00:31:20 in small populations the proto-human population. 472 00:31:20 --> 00:31:24 I just told you that certain polymorphisms die out because of 473 00:31:24 --> 00:31:28 this genetic drift, because of these stochastic events. 474 00:31:28 --> 00:31:32 And so, the founding human population could have had 20, 475 00:31:32 --> 00:31:36 50,100 individuals in it, but one woman's mitochondrial DNA happened 476 00:31:36 --> 00:31:41 because of these accidents to dominate, so that now, 477 00:31:41 --> 00:31:45 all of us have the same, are the descendents of her 478 00:31:45 --> 00:31:49 mitochondrial DNA. Clearly, in the intervening time 479 00:31:49 --> 00:31:53 since 150,000 years ago, accumulated mutations have, 480 00:31:53 --> 00:31:57 have altered subtly the mitochondrial DNA genome, 481 00:31:57 --> 00:32:02 so there's polymorphisms, And so one can make, 482 00:32:02 --> 00:32:08 one can drive phylogenies of different kinds of mitochondrial DNA, 483 00:32:08 --> 00:32:13 and look at the relatedness between different clades, 484 00:32:13 --> 00:32:19 different groups, of women in modern-day Europe. 485 00:32:19 --> 00:32:24 70% of Finish men, in Finland, have a y-chromosome 486 00:32:24 --> 00:32:30 polymorphism that is otherwise virtually unheard of in the rest of 487 00:32:30 --> 00:32:36 Europe. 70% of Finish men, now what does that mean? 488 00:32:36 --> 00:32:38 Well, to me to means that those 70% of Finish men descended from a 489 00:32:38 --> 00:32:41 common ancestor, a male who lived around, 490 00:32:41 --> 00:32:44 if you look at the sequences, who lived around two or three 491 00:32:44 --> 00:32:47 thousand years ago, and who, for some reason, 492 00:32:47 --> 00:32:50 became the ancestor of all the people living in modern Finland. 493 00:32:50 --> 00:32:52 That's extraordinary. There's four million people living in Finland 494 00:32:52 --> 00:32:55 today, and the males all have their inherit, inherit their y-chromosome 495 00:32:55 --> 00:32:58 from that man, we don't know exactly where he lived, 496 00:32:58 --> 00:33:01 But obviously the modern Finish 497 00:33:01 --> 00:33:05 population descends from a very small founder-group who came into 498 00:33:05 --> 00:33:09 what we call, modern Finland, relatively recently, maybe two-two 499 00:33:09 --> 00:33:13 and a half thousand years ago, and thereafter, did not freely 500 00:33:13 --> 00:33:16 interbreed with the rest of the European population. 501 00:33:16 --> 00:33:20 How do we know that? Because that y-chromosomal 502 00:33:20 --> 00:33:24 polymorphism is not present elsewhere, it's only present in 503 00:33:24 --> 00:33:28 Finland. So it was a genetic, and obviously linguistic, isolate. 504 00:33:28 --> 00:33:32 So where do we all come from, 505 00:33:32 --> 00:33:36 all of us human beings? How closely related are we to one another? 506 00:33:36 --> 00:33:40 Here's, here's a measurement of the distances between different 507 00:33:40 --> 00:33:44 mitochondrial DNA's from different branches of humanity. 508 00:33:44 --> 00:33:49 And what you see is something really quite extraordinary and 509 00:33:49 --> 00:33:53 stunning. Here, you'll see that the people, 510 00:33:53 --> 00:33:57 the non-African lineages here and here, are actually relatively 511 00:33:57 --> 00:34:01 closely related to one another. But if you look at the people who 512 00:34:01 --> 00:34:04 live in Africa, down here, there is enormous genetic 513 00:34:04 --> 00:34:08 diversity. Look how far these evolutionary branches reach back, 514 00:34:08 --> 00:34:11 look how long these are. The distance of these branches, 515 00:34:11 --> 00:34:14 of these roots, determines how far, how distantly related these 516 00:34:14 --> 00:34:18 individuals are, one to the other. 517 00:34:18 --> 00:34:21 And on the basis of that, and on the basis of a lot of other 518 00:34:21 --> 00:34:24 auxiliary genetic information, we can conclude that Africa was the 519 00:34:24 --> 00:34:28 site where genetic diversification was generated during 520 00:34:28 --> 00:34:31 human evolution. And that what happened, 521 00:34:31 --> 00:34:35 as a consequence of that diversification, 522 00:34:35 --> 00:34:39 is starting over the last 40, 50, 60,000 years ago, different 523 00:34:39 --> 00:34:42 populations, different sub-populations, 524 00:34:42 --> 00:34:46 small, isolated sub-populations, migrated out of Africa, took a very 525 00:34:46 --> 00:34:49 small sub-set of the polymorphisms with them, and became the 526 00:34:49 --> 00:34:53 founder-populations of a whole variety of whole different 527 00:34:53 --> 00:34:57 modern-day populations. These populations here are largely 528 00:34:57 --> 00:35:00 Mongoloid, these populations here are largely Caucasian, 529 00:35:00 --> 00:35:04 and here, we see that in Africa there's enormous genetic 530 00:35:04 --> 00:35:07 diversity. And by the way, 531 00:35:07 --> 00:35:11 all the genes that are present here, the alleles that are present here, 532 00:35:11 --> 00:35:15 can also be found in Africa, but in relatively small proportions 533 00:35:15 --> 00:35:19 in Africa. And we know this kind of diversity exists both for the 534 00:35:19 --> 00:35:23 mitochondrial DNA, and here's for the y-chromosomal DNA, 535 00:35:23 --> 00:35:26 again, we look for polymorphisms. And this is not a very good 536 00:35:26 --> 00:35:30 overhead, again, the reproduction was not very good, 537 00:35:30 --> 00:35:34 but what I'm showing you is that the evolutionary, the depth of these 538 00:35:34 --> 00:35:38 evolutionary branches is enormous in Africa, yet in other parts of the 539 00:35:38 --> 00:35:42 globe, people are much more closely-related to one another. 540 00:35:42 --> 00:35:45 Some people argue on the basis of the genetic-relatedness of western 541 00:35:45 --> 00:35:48 and northern Europeans, that the modern European population 542 00:35:48 --> 00:35:52 is largely descended from about 20 couples that moved into Europe about 543 00:35:52 --> 00:35:55 10,000 years ago, eight to ten thousand years ago, 544 00:35:55 --> 00:35:58 at the time when agriculture was introduced into Europe from the 545 00:35:58 --> 00:36:02 middle east, just on the basis of looking at these y-chromosomal 546 00:36:02 --> 00:36:06 sequences. And so, we human beings arose, 547 00:36:06 --> 00:36:11 even though we are reasonably distantly related to one another on 548 00:36:11 --> 00:36:16 this graph, keep in mind that we as a species, are enormously close to 549 00:36:16 --> 00:36:21 one another because of the youth of this, of our species. 550 00:36:21 --> 00:36:26 If you look at our, the time of this diversification was probably 551 00:36:26 --> 00:36:31 sometime between 80-100, 00 years ago, so how did it all 552 00:36:31 --> 00:36:36 happen? We can even figure out the history of humanity by beginning to 553 00:36:36 --> 00:36:42 look at these different kinds of polymorphisms. 554 00:36:42 --> 00:36:45 A long time ago, individuals went out from Africa, 555 00:36:45 --> 00:36:49 maybe starting 100,000 years ago, maybe starting more recently, 556 00:36:49 --> 00:36:53 and went across the southern rim of Eurasia, and we know already, 557 00:36:53 --> 00:36:56 we find archeological remains of Aborigines in Australia between 558 00:36:56 --> 00:37:00 40-60,000 years ago. And by the way, those people are 559 00:37:00 --> 00:37:04 very distantly related to the rest of us, having left and not 560 00:37:04 --> 00:37:08 intermingled with the rest of humanity for a very long 561 00:37:08 --> 00:37:11 period of time. There were Aborigines in Australia, 562 00:37:11 --> 00:37:15 already at a time when our ancestors, to the extent we had ancestors in 563 00:37:15 --> 00:37:19 Europe, were still battling the Neanderthals, who only died out 30, 564 00:37:19 --> 00:37:23 00 years ago. You may know by the way, you may have read in the 565 00:37:23 --> 00:37:27 newspaper, about a month ago, they discovered skeletons of very 566 00:37:27 --> 00:37:30 small people on an island Indonesia. In fact, those were probably not 567 00:37:30 --> 00:37:34 even homosapiens, those were probably a precursor 568 00:37:34 --> 00:37:38 species, because we know over the last two million years, 569 00:37:38 --> 00:37:42 there have been hominoids, look like human beings but are 570 00:37:42 --> 00:37:46 precursors, who might migrated out of Africa, who dispersed throughout 571 00:37:46 --> 00:37:50 Asia, and who eventually became extinct, 572 00:37:50 --> 00:37:53 So that the only modern human who exist are the descendents of this 573 00:37:53 --> 00:37:57 out migration that began about 100, 00 years ago. We know that about 15, 574 00:37:57 --> 00:38:00 00 years ago some of these people ended up going over here, 575 00:38:00 --> 00:38:04 to crossing in four different waves of migration, you can see it from 576 00:38:04 --> 00:38:08 the DNA, into the western hemisphere. 577 00:38:08 --> 00:38:12 Amerindians, that is, American Indians, Native Americans, 578 00:38:12 --> 00:38:16 are genetically rather homogenous. Why? Because they all descend from 579 00:38:16 --> 00:38:21 very small founder populations that came into the western hemisphere 580 00:38:21 --> 00:38:25 relatively recently. And there's enormous genetic 581 00:38:25 --> 00:38:30 homogeneity among different subgroups of individuals here in 582 00:38:30 --> 00:38:34 South America. Speaking of South America, 583 00:38:34 --> 00:38:39 if you look in some parts of Venezuela, what you find is that the 584 00:38:39 --> 00:38:43 mitochondrial DNA is largely of Indian-origin, 585 00:38:43 --> 00:38:48 but the y-chromosomal DNA is largely of European origin. 586 00:38:48 --> 00:38:52 So, what happens there, that's a testimonial to the tragic 587 00:38:52 --> 00:38:56 fate of the Indians, where the conquistadors from Spain 588 00:38:56 --> 00:39:00 came in, killed all the men, and took all the women, to be their 589 00:39:00 --> 00:39:04 brides. How else can you explain the fact that there's no Indian 590 00:39:04 --> 00:39:08 y-chromosomes, there's all, there is instead only 591 00:39:08 --> 00:39:12 European y-chromosomes. And here you can begin to see what 592 00:39:12 --> 00:39:16 happened here in New York, as well. 40,000 years ago people 593 00:39:16 --> 00:39:21 started trickling into Europe, and they hung around there for the 594 00:39:21 --> 00:39:26 next 30,000 years, pretty much on their own. 595 00:39:26 --> 00:39:30 The remnants of those people who came in, we know from DNA, 596 00:39:30 --> 00:39:35 are the Basques who live in northern Spain, who speak, 597 00:39:35 --> 00:39:40 by the way, a non-indo European language. 598 00:39:40 --> 00:39:43 They're the relics of this initial settlement by modern humans of 599 00:39:43 --> 00:39:47 Europe, starting 40, 00 years ago. And they had the 600 00:39:47 --> 00:39:50 continent for themselves for the next 30,000 years, 601 00:39:50 --> 00:39:54 until this new founder population came in, about 10, 602 00:39:54 --> 00:39:57 00 years ago. Here's the names of the girls who were in that group, 603 00:39:57 --> 00:40:01 Ursula and Katrine and Zenya, Tara, Jasmine, and Velda, and they became 604 00:40:01 --> 00:40:04 the modern agriculturalists, and swamped out the people who were 605 00:40:04 --> 00:40:08 there 40,000 years ago, who now only survive as a relic 606 00:40:08 --> 00:40:12 population. Here's a fun story I like to tell 607 00:40:12 --> 00:40:16 each year, and it's about the Cohen and y-chromosome, 608 00:40:16 --> 00:40:21 and you'll see what an amusing story this is, just from genetics. 609 00:40:21 --> 00:40:25 Now the name Cohen, in Hebrew means, a high priest, 610 00:40:25 --> 00:40:29 and you've heard people named Cohen, it's not such an uncommon name among 611 00:40:29 --> 00:40:34 the Jews. And it says, in the Bible, in Genesis and Exodus, 612 00:40:34 --> 00:40:38 that all the high priests in the Bible are the descendents of Aaron, 613 00:40:38 --> 00:40:43 the brother of Moses. And it's also been the practice for 614 00:40:43 --> 00:40:47 the last 3,000 years, that the only person who can become, 615 00:40:47 --> 00:40:51 the only male who can become a Cohen, is the son of a Cohen. 616 00:40:51 --> 00:40:56 In other words, you cannot be adopted into a family and acquire 617 00:40:56 --> 00:41:00 the name Cohen. And if that's all true, 618 00:41:00 --> 00:41:05 and if the Bible is true, and Aaron lived 3,000 years ago, 619 00:41:05 --> 00:41:09 whatever his name was, then it should be the case that all male 620 00:41:09 --> 00:41:14 Cohen's should have the same y-chromosome, right? 621 00:41:14 --> 00:41:17 Because they all descend, their family name is Cohen, 622 00:41:17 --> 00:41:21 they could only get it from their father, they could only get their 623 00:41:21 --> 00:41:25 y-chromosome from their father, so they should all have the same 624 00:41:25 --> 00:41:29 y-chromosome. Of course, you say that can't really be the 625 00:41:29 --> 00:41:32 case, because we know in this country, in this country, 626 00:41:32 --> 00:41:36 between five and ten percent of people, on average, 627 00:41:36 --> 00:41:40 are sending Father's Day cards to the wrong person. 628 00:41:40 --> 00:41:44 What does that mean? Non-paternity. 629 00:41:44 --> 00:41:48 When you do genetic counseling of family these days, 630 00:41:48 --> 00:41:53 one of the strictures is, that you never tell the family if 631 00:41:53 --> 00:41:57 the children have genetic polymorphisms that don't match that 632 00:41:57 --> 00:42:02 of the person whom they think is their father. They don't look like 633 00:42:02 --> 00:42:06 their, the person whom they regard as father, but that's always assumed 634 00:42:06 --> 00:42:11 to be a role of the genetic dice. So, how is that relevant? Well, 635 00:42:11 --> 00:42:16 let's talk about this descent from Aaron, who lived 3,000 years ago. 636 00:42:16 --> 00:42:20 We're talking about the y-chromosome being passed from one generation to 637 00:42:20 --> 00:42:24 the next, just like the family name. So what happened, what would happen 638 00:42:24 --> 00:42:29 if sometime over the last 3, 00 years, Mrs. Cohen had a dalliance, 639 00:42:29 --> 00:42:33 had an affair, with a television repairman, 640 00:42:33 --> 00:42:37 or the milkman, or the mailman, and never told Mr. Cohen? The 641 00:42:37 --> 00:42:42 y-chromosome, which her son thought he was getting from Dad, 642 00:42:42 --> 00:42:46 wouldn't be coming from Dad, it'd be coming from this other, 643 00:42:46 --> 00:42:51 the milkman or the mailman, and it wouldn't be a Cohen-y chromosome 644 00:42:51 --> 00:42:55 unless, by chance, the mailman or the milkman also 645 00:42:55 --> 00:43:00 happened to be a Cohen, [LAUGHTER], it could happen. 646 00:43:00 --> 00:43:04 But the chances are, roughly speaking, Cohen's are only 647 00:43:04 --> 00:43:08 four percent of all Jews, so the chances are against that 648 00:43:08 --> 00:43:12 happening. OK, so they did this experiment, 649 00:43:12 --> 00:43:16 and this is really astounding experiment. They went, 650 00:43:16 --> 00:43:20 the story is they went to a beach in Tel Aviv, I don't know whether they 651 00:43:20 --> 00:43:24 actually did that or not, and they picked up, they picked up 652 00:43:24 --> 00:43:28 100 male Cohen's who were Ashkenazi , Ashkenazi means their ancestors came 653 00:43:28 --> 00:43:32 from central Europe, over here. And they picked up 100 Sefardi 654 00:43:32 --> 00:43:36 Cohen's, and the Sefardi Cohen's come from Spain, 655 00:43:36 --> 00:43:40 North Africa, Egypt, Yemen, Iraq, Iran, Uzbekistan, 656 00:43:40 --> 00:43:44 Central Asia. And the last time that the Iraqi Cohen's and the 657 00:43:44 --> 00:43:48 Ashkenazi Cohen's were interbreeding, were about 500 BC, 658 00:43:48 --> 00:43:52 at the time of the Babylonian XL, so they've been apart a long time. 659 00:43:52 --> 00:43:56 And they looked at their y-chromosomes, 660 00:43:56 --> 00:44:00 and what they found was that 70% of the y-chromosomes of these male 661 00:44:00 --> 00:44:04 Cohen's, 70% of the Cohen's shared the same y-chromosome. 662 00:44:04 --> 00:44:07 Well, the same y-chromosome was present only in 15% of non-Cohen, 663 00:44:07 --> 00:44:11 Israeli Jews. Now think about that for a second. 70% of these men had 664 00:44:11 --> 00:44:14 the same y-chromosome, of course they didn't know they had 665 00:44:14 --> 00:44:18 the same y-chromosome, all they knew was that they had the 666 00:44:18 --> 00:44:22 same family name. And what that means, 667 00:44:22 --> 00:44:25 inescapably, is that over a period of two or three thousand years, 668 00:44:25 --> 00:44:29 it was hard to trace with exactitude when the common male ancestor lived, 669 00:44:29 --> 00:44:32 over a period of two or three thousand years, 670 00:44:32 --> 00:44:36 somehow the milkman and the mailman stayed away from Mrs. 671 00:44:36 --> 00:44:40 Cohen, or Mrs. Cohen was unusually virtuous. 672 00:44:40 --> 00:44:43 Because keep in mind, any single affair with the milkman 673 00:44:43 --> 00:44:47 or the mailman, over 3,000 years, 674 00:44:47 --> 00:44:50 would've broke this chain of inheritance, any single incidence of 675 00:44:50 --> 00:44:54 non-paternity. It's a really astounding story, 676 00:44:54 --> 00:44:57 and it's hard, there can be no artifact to it, 677 00:44:57 --> 00:45:01 there's no bias in it, there's no other way to explain it. 678 00:45:01 --> 00:45:04 And you can begin to find similar stories of families in England, 679 00:45:04 --> 00:45:08 where males are tenth cousins of one another, they have the same family 680 00:45:08 --> 00:45:12 name, and they also have the same y-chromosome. 681 00:45:12 --> 00:45:17 The most amusing commentary on this stems from a tribe that lives in 682 00:45:17 --> 00:45:22 southern Africa, and these people are called, 683 00:45:22 --> 00:45:27 Lemba, L-e-m-b-a. And the, the myth of the Lemba is that they descend 684 00:45:27 --> 00:45:32 from Jews who came down from the north, Jewish traitors. 685 00:45:32 --> 00:45:37 So just for the hell of it, some geneticists went down and drew 686 00:45:37 --> 00:45:42 blood from the male Lembas, and there's four casts of Lembas, 687 00:45:42 --> 00:45:47 there's the ruling class, there's the warriors, there's the farmers, 688 00:45:47 --> 00:45:51 the merchants, I don't know. And what they found was that all 689 00:45:51 --> 00:45:55 members of the, almost all members of the ruling 690 00:45:55 --> 00:45:59 cast among the Lembas, had the same y-chromosome, 691 00:45:59 --> 00:46:02 and the y-chromosome had exactly the same polymorphisms of the Cohen 692 00:46:02 --> 00:46:06 y-chromosome. No one in the other, no males in the other three casts 693 00:46:06 --> 00:46:10 had, or very few, had otherwise this y-chromosomal 694 00:46:10 --> 00:46:14 polymorphism. Go figure, I don't know what's going on. 695 00:46:14 --> 00:46:17 Now did those people look Jewish? Well, they looked like everybody 696 00:46:17 --> 00:46:20 else around them, because if there was a Mr. 697 00:46:20 --> 00:46:23 Cohen who came down there, three or four hundred years ago, 698 00:46:23 --> 00:46:27 and married in, he obviously married one of the local population. 699 00:46:27 --> 00:46:30 And there were no other people around from, coming in from the 700 00:46:30 --> 00:46:33 north, to marry to, so that 99% of the males in this 701 00:46:33 --> 00:46:37 ruling cast, who have the Cohen y-chromosome, 99% of their genes 702 00:46:37 --> 00:46:40 come from the local population, the only thing they inherited from 703 00:46:40 --> 00:46:44 Mr. Cohen was the y-chromosome. Where else would they get their 704 00:46:44 --> 00:46:48 genes? There wasn't a massive migration from the middle east down 705 00:46:48 --> 00:46:52 to the Lemba tribes, probably just one man came down 706 00:46:52 --> 00:46:56 selling trinkets, or who-knows-what, 707 00:46:56 --> 00:47:00 television sets, or VCRs, sometime over the last three or four 708 00:47:00 --> 00:47:04 hundred years. And somehow, for reasons that we 709 00:47:04 --> 00:47:08 have no idea, he became the ancestor of this cast of people in this tribe 710 00:47:08 --> 00:47:12 in the middle of Africa. And so you have stories that you 711 00:47:12 --> 00:47:16 begin to pick up, which are stranger than fiction, 712 00:47:16 --> 00:47:20 some of the weirdest stories that you've ever heard of in your life. 713 00:47:20 --> 00:47:24 Imagine having 3,000 years of uninterrupted transmission from, 714 00:47:24 --> 00:47:28 without a single case of non-paternity. 715 00:47:28 --> 00:47:32 It didn't happen all the cases, because I didn't say 100% of the 716 00:47:32 --> 00:47:36 Cohen men had it, on 30% of the occasions, 717 00:47:36 --> 00:47:40 there must have been some snipping of this chain of transmission. 718 00:47:40 --> 00:47:52 And keep in mind that this chain of transmission happened over a period 719 00:47:52 --> 00:48:04 of enormous political and upheaval, over the last 3,000 years. The 720 00:48:04 --> 00:48:17 middle east, and Europe, and North Africa, have not been 721 00:48:17 --> 00:48:29 tranquil places over that period of time. Enormous population dispersal, 722 00:48:29 --> 00:48:42 and confusion, and displacement, 723 00:48:42 --> 00:48:54 and yet we now begin to look, by looking at the DNA, we can begin 724 00:48:54 --> 00:49:07 to see all kinds of really interesting things. 725 00:49:07 --> 00:49:11 Next, on Friday, Eric is going to talk with you, 726 00:49:11 --> 00:49:16 I believe, on Monday, as well. And Wednesday, we're going to talk about 727 00:49:16 --> 00:49:20 a related topic, which is, how do all, 728 00:49:20 --> 00:49:25 how do these human genetic differences have implications for 729 00:49:25 --> 00:49:29 the way we think about one another, and the way that we will develop? 730 00:49:29 --> 49:34 See you then, a week from today.