Rediscovering Biology: Molecular to Global Perspectives
Human Evolution Expert Interview Transcript: Christopher Wills, Ph.D.
Professor of Biology
Professor of Biological Sciences at the University of California at San Diego. He studies intriguing questions about evolution, such as, what is the evolutionary history of sex? Perhaps it originated as the incorporation by cells of exogenous genetic material. He is the author of several books, including Children of Prometheus: the Accelerating Pace of Human Evolution.
Christopher Wills, Ph.D., is a Professor of Biological Sciences at the University of California at San Diego. He studies intriguing questions about evolution, such as, What is the evolutionary history of sex? Perhaps it originated as the incorporation by cells of exogenous genetic material. He is the author of several books, including Children of Prometheus: The Accelerating Pace of Human Evolution.
How would you define “phylogeny”?
Phylogeny is the relationship between organisms: how they are related to each other over evolutionary time. If you look at the ways in which organisms have descended from common ancestors, you can build what a “gold” phylogenic tree is, which essentially allows you to trace them back to that common ancestor, even though you may not even have a fossil of the common ancestor.
You can nonetheless infer that these organisms had a common ancestor by looking at the resemblances between them, by looking at the resemblances between their DNA molecules. You can then begin to get a measure of the phylogenic resemblance between organisms, even organisms that are very different from each other.
Can you define “Australopithecus”?
An australopithecine is a southern ape. The term doesn’t have anything to do with Australia. It means instead “austral,” being, of course, Latin for southern, or Southern Hemisphere. Australopithecines were first found by Raymond Dart back in the 1920s in South Africa, and they have since been found in southern Africa, in East Africa, and one or two places elsewhere in Africa. They have not ever been found outside of Africa.
How about the term “Hominid”?
The great apes are called the hominoids. They’re part of the family Hominoidea. The hominids are a subgroup of that family, which includes ourselves, and our very closest relatives. So the chimpanzee is our closest living relative, but it’s a hominoid.
Our hominid relatives have gone extinct. The australopithecines were a hominid relative, Homo erectus, the Neanderthals, some of the other close relatives of ours that lived in Africa and in parts of the Old World that are now all extinct were all hominids. So we are the only living member of that particular group.
How would you describe Mosaic evolution?
Mosaic evolution is the idea that different genes in organisms, different parts of organisms, may evolve at different rates. So you’ve got a situation in which some feature of an organism might evolve very quickly; other features of the organism might evolve much more slowly. That’s a rather obscure term though. So if you look at the hominid fossil record, for example, you’ll find that many skulls might have very human-like features and very ape-like features, a funny mix of the two, and in fact that kind of thing has been found most recently in that fossil that they turned up in Chad just a few weeks ago, which has a rather human-looking face but the back of the skull looks very much like a chimpanzee. That kind of difference essentially between different parts of this animal suggests that perhaps these different features were evolving at different rates, or perhaps were evolving and then disappearing again. Ah. There were so many different ways in which you can get a mixture of different types here.
And you mustn’t forget, too, that just because an animal sort of looks partly human, parts of its skull look human, that animal is still a perfectly functional animal. It’s not as if it were some kind of mashed together mix of humans and apes. Instead, it was a perfectly viable, functioning, very highly adapted organism in its own right, so we’re imposing this idea of mosaic evolution on these fossils I think.
Could you explain the concept of a molecular clock?
The concept of a molecular clock first emerged back in the 1960s when people first began to sequence proteins in reasonable numbers from different organisms. And they found that among the hemoglobin molecules, for example, if you looked at hemoglobin molecules from different mammals and you tried to relate the degree of divergence of these molecules to the degree of divergence of the animals, that you could match what you get from the fossil record. It was a very good match. Such a good match that it’s been suggested that many molecules evolve in a fairly clock-like fashion, that they change over time in a fairly regular way. A certain number of changes in the molecules will happen every few million years.
Some molecules evolve to a fast clock; some molecules evolve to a slower clock. And some molecules seem to speed up and slow down. So the clock is not a terribly accurate clock. It’s not as if all molecules are marching to the same drummer. Nonetheless, the clock allows you to get some idea of how quickly evolution has happened.
What is mitochondrial DNA?
Mitochondrial DNA is the small piece of DNA that is found inside our mitochondria. Our mitochondria are little powerhouses in our cells. These are the little structures that make ATP and other goodies that the cell depends on for survival.
The mitochondria are, as the audience probably knows, descendants of free-living bacteria that came to live inside our cells probably about two and a half billion years ago. And since that time they’ve lost most of their genes, so these little descendants of bacteria, without which we could not survive as multi-cellular animals, these little descendants of bacteria which supply us with so much of our energy have lost 90-odd percent of their genes, so they’re only left with something like 27 genes in them, in the current human mitochondrial genome. And that’s essentially what’s left.
The other genes have migrated into the other chromosomes, or they’ve been lost. So what you’ve got is a very stripped-down thing. This mitochondrial genome is small enough that it can be sequenced fairly easily in its entirety, which allows you to use the mitochondrial chromosome in those phylogenic studies that we talked about a moment ago.
Explain the inheritance of the mitochondrial genome?
Mitochondrial DNA is inherited differently from most DNA. Most DNA is mixed up when the sperm and egg fuse, the DNA of the sperm and the egg are mixed together, and then when that individual grows up and starts to make sex cells, eggs or sperm, those cells then scramble up the DNA even further, so you then end up with each egg or each sperm having its own unique set of genes.
The mitochondrial genes, in contrast, are all locked together on the mitochondrial chromosome, and they’re passed down from one generation to the next in most mammals-most of the time. And that inheritance is maternal inheritance. The reason being that the egg has mitochondria in it, the sperm have mitochondria too, but the mitochondria get lost when the sperm fertilizes the egg.
So the sperm mitochondria get lost, the sperm fertilizes the egg, the sperm’s nuclear genes are combined with the nuclear DNA in the egg so that the egg and the sperm which fused to make you contained only the egg’s, only your mother’s, mitochondrial genes.
Can you describe the “Replacement hypothesis”?
We’re talking here about two different hypotheses about the origin of humans. One of them is the so-called “replacement hypothesis,” which suggests that modern humans arose fairly recently in Africa, spread from Africa, and replaced all the other hominids that were living in the Old World, perhaps within the last hundred thousand years or so.
The “multiregional hypothesis,” in contrast, looks at the origin of humans in a different way. It suggests that human evolution occurred over a fairly broad front and that there was a lot of genetic exchange between different human groups in Africa, outside of Africa, between Africa and the rest of the Old World, exchanging genes between different human groups so that they all essentially evolved more or less in synchrony, and there was no tremendous replacement. The replacement hypothesis, as you know, is the one that is currently favored because the mitochondrial data gives strong evidence — strong support to that.
But I think people are now beginning to realize that it is not entirely true, that some genes from the hominids of the Old World may have leaked into our gene pool before this last migration out of Africa. Alan Templeton at the Univ. of Michigan has looked very carefully at this and has found some very suggestive evidence that there was, in fact, an earlier mixture of genes.
So my own take on this is that, yes, there was largely a replacement, but there was a little bit of multiregionality as well. There was a little bit of genetic information coming in from other gene pools, other than those of more modern humans in Africa.
Talk a bit about the recent findings in Georgia and Chad.
These are very exciting finds, both of them, but different. Their implications are rather different.
The Georgia find is one that suggests that surprisingly small-brained people left Africa perhaps close to two million years ago, and began to migrate into other parts of the Old World. The size of the brain is problematic in humans. It can vary over a wide range. The latest skull from Georgia has a brain capacity that is certainly smaller than that of any present-day human. It’s a brain of about 600 cubic centimeters compared with on average 12 to 14 hundred cubic centimeters for most modern humans, so we’re talking about a brain half or less than half the size that of modern humans. But that might be because that individual was small and still growing. The interesting thing, though, about this is that these people, found in what used to be Soviet Georgia and is now the Republic of Georgia, these people had features that remind one of a transitional hominid known as “Homo habilis.” It was first found by Louis and Mary Leakey years ago, back in the 1960s. Homo habilis, which means “handyman,” was presumed to be a transition between the australopithecines that we talked about a little earlier, and Homo erectus, which in turn may be segued into Homo sapiens at some point subsequent to that time.
Homo habilis had a small brain but a very human-like face and has been found in similar strata to tools, although a direct connection between Homo habilis and tool use has not been made. In Georgia, they have in fact found some rather primitive stone tools suggesting that in fact, these people were tool users.
The striking thing about this is that people had assumed that people migrated out of Africa because they got great big brains and they, you know, got to be restless because they were so smart and they wanted to see what was on the other side of the world. And that they had to have big brains to make the kind of technology that they would need to take with them on long-distance travel.
Well, it now looks as if small-brained people could do the same, which in turn suggests-to me, anyway-that maybe the size of the brain isn’t as important perhaps as manual dexterity, the ability to travel long distances, the ability to remember where you’ve been, the ability to communicate with your fellows-all these things I suspect could be accomplished by hominids with smaller brains than we have. And my guess would be that the group of people that had been found now in Georgia could have been rather more like us than we had imagined a few years ago. And having a gigantic brain isn’t necessarily a requirement for being pretty close to being a modern human.
Then there’s Chad of course, in West Africa. This is a very interesting find, because the fossils were found in a very dry, desert area, and they found a very nice skull. The picture looks most impressive.
This find is exciting because of the probable date. We’re talking here about hominids with a very human-like face and a very chimpanzee-like brain case, living perhaps as long as seven million years ago. And you can’t be sure of this date. You can be a lot surer of the dates in East Africa, because you have dating methods that involve volcanic eruptions, so you can get a pretty accurate idea of when these hominids lived. In West Africa you can’t really do that.
But you can look at the animals that have been found in association with this hominid fossil, and they can be matched up with similar animal collections or animal communities, fossil communities that had been found in other parts of Africa, and when you do that, you get a date somewhere between six and seven million years old.
Now the interesting thing about that is I think twofold. First of all, these hominids were surprisingly advanced, at least so far as their facial features were concerned. They were surprisingly human-like in that regard. They had small brains: only perhaps 400 cubic centimeters. I don’t think anyone is able to measure that really accurately but they weren’t very big brains.
But they look surprisingly advanced compared with the previous record holders, in particular, Australopithecus ramidus, and the other very old fossils that had been found in East Africa that have much more primitive features. So here you have a surprisingly advanced hominid living as long ago as seven million years ago.
Now the fossil record and the molecular record match up fairly well. You can work out from a variety of methods using the molecular clock that humans and chimpanzees probably diverged — their ancestors probably diverged about between five and six million years ago. But now we find a possible seven million-year-old fossil that is obviously beyond that divergence point so there are two possibilities.
One is that we’re gonna have to change the molecular clock a little bit, recalibrate it and move it back in time, which wouldn’t surprise me if that were the case. The other possibility is that this hominid in Chad was an independent evolutionary branch that developed hominid features and then went extinct. The later evolution in East Africa of hominids that eventually ended up as Homo sapiens may have been an independent branch, and there could have been a lot of other independent branches that were lost at around that time.
I don’t know what the answer to that is going to turn out to be. A connection between these, if you could find that a connection, a series of fossil finds that would link up this surprisingly advanced very old fossil with the equally advanced fossils in East Africa, would be a very exciting series of finds, but that would depend on chance. You never know when you’re going to find the right fossil.
I think, though, that all these discoveries show that we have a lot to learn about the timing of human evolution, about the branches of human evolution, how many different groups may have moved in the direction of bigger brains and greater manual dexterity and then went extinct long before we have any good fossil records of these groups of peoples. I think we’re going to see that our evolution was fascinating, because if in fact, it turns out there were lots of different branches that are all doing much the same thing, what drove all these branches in this direction? Why didn’t the great apes go the same way? What was it about this lineage, this hominid lineage, that led to so many experiments, so many evolutionary experiments?
And my own guess-and I wrote a book about it a few years ago-is that right from the beginning of the hominid lineage, we were driven by a kind of brain-culture feedback loop which fed back to our brains and our bodies and essentially drove us in the direction of bigger brains, more cleverer hands, more upright posture, better communication skills-all the things that we think of as being quintessentially human may have been driven in many different lineages independently, leading towards this kind of thing.
The essence, I think, of our current understanding of human evolution is that we should begin to look at some of these parallel groupings as cases of parallel evolution. The Neanderthal, for example, appear to have evolved independently of other human lineages over the last million or so years in western Europe towards big brains, towards greater communication skills, as far as we can tell, towards elaborate culture and did so independently of Homo sapiens, which came in very late.
And there’s another case in which I suspect of this kind of parallel evolution. The Neanderthals, too, went extinct. But we don’t know why, and we have yet to discover any genes that they have left behind, but they may have done so.
Can you comment on the group of scientists to which you belong that regularly discusses human evolution?
Yes, it was a group that Fred Gage and Ajit Varki put together five or six years ago now. The idea was for us to get together periodically and talk about human evolution and how it happened. And it’s a sort of a private group. We’ve sort of extended the membership now, so we have a lot of people from around the world involved in that, and Ajit has been very adroit in getting funds to have a series of meetings.
What we do essentially is “blue sky” it a lot, and as a consequence, we’re very hesitant to have outsiders join the group because, you know what would happen if reporters turned up. They could take things out of context or talk about things that had been discussed in the group that are really not ready for primetime. So we sort of tried to keep it a private group as much as we could. And it’s been enormously useful, and it’s generated, in my case, several research directions that I found very productive, and I think other people have had the same experience. It’s a very exciting group.
Why is it so important to incorporate different disciplines?
Well, I think it’s very important for the simple reason that human evolution is a very controversial topic. Everyone has their own idea about how it works, and they will defend that idea to the death, if necessary. What you’ll find in narrower meetings, let’s say meetings of anthropologists or meetings of molecular biologists, is that people argue about things that, if somebody else were present, could probably be resolved.
The molecular biologists probably know nothing about paleoclimate. The paleoclimatologists know nothing about molecular biology. But put them together and all kinds of things click into place because things that were inexplicable in one field suddenly are illuminated by what people have discovered in another field. And as a consequence over the years we’ve had surprisingly few arguments. For the most part, we have treated this as an exploration of exciting fields of knowledge that are all linked together in all sorts of interesting ways that we would practically not even know about if you didn’t have a wide variety of people attending the meetings.
How can one use molecular DNA as a chronometer?
The mitochondrial chromosome, as I said, is inherited maternally and it is-so far as we can tell at least-not recombined the way the nuclear genes tend to be mixed up and recombined every generation. So it is inherited as a unit.
And essentially, then, as these mitochondrial chromosomes are passed down from one generation to the next they begin to diverge, not because they’re mixing up their genes but because of accumulating mutations, so that as time goes on, you might have mitochondrial chromosome of a particular type which is then left to many, many progenies in the future. And as time goes on, these different chromosomes begin to diverge from each other; these different copies of that chromosome begin to diverge from each other. The longer the period of time the greater the divergence. So that’s turned out to be very useful in understanding how human evolution might have happened, because any human group essentially can trace its mitochondrial chromosomes back to one ancestor. So small human groups, for example, Australian aboriginals or African pigmies or people who have been isolated from the rest of the human gene pool for some period of time, can trace the time at which they separated from the rest of the human population. If you look at their mitochondrial chromosomes, you may be able to trace them back to a relatively recent single common ancestor, perhaps a few tens of thousands of years ago. If you look at the whole human species, you can do the same thing, but then, of course, that mitochondrial ancestor lived much longer ago.
Now that mitochondrial ancestor doesn’t mean that we can trace these mitochondrial chromosomes back to some single individual who was the only human being that lived back at that time. The Mitochondrial Eve is that mitochondrial ancestor. The Mitochondrial Eve is the woman who lived perhaps two to three hundred thousand years ago, from whom all our mitochondrial chromosomes have descended. But she didn’t link up with some Adam and live in a Garden of Eden. She was one of a group of people, and probably lots of different groups of people, living at that time.
All the other people living at that time — their mitochondrial chromosomes got lost by chance. Hers was the only one that survived. But there might have been a hundred thousand, tens of thousands of people living at that time, all of whom, by chance, did not pass their mitochondrial chromosomes down to the present. They did, however, pass their nuclear genes down to the present. So while her mitochondrial chromosome is the one that we all have, or descendants of which we all have, the nuclear genes that we have can be traced much further back than that. Some nuclear genes, in fact, can be traced back to before there was a human species and some, in fact, can be traced back to before there were mammals. I mean we’re talking nuclear genes that go back a long, long way in time.
So the Mitochondrial Eve, then, is something that the popular press has again and again represented as being a woman who was the ancestor of us all, and that’s not true because she was only the ancestor of all our mitochondrial chromosomes, which is only a tiny little fraction of our DNA. And the nuclear genes, they’ll all trace back to that woman.
The other canard that is being told about the Mitochondrial Eve is that she was the first modern human. Oh, we don’t know that at all. The Mitochondrial Eve probably I think predated people whom we would think of as being very much like ourselves. You go back to 300,000 years to people living at that time were probably distinctly different from us. And 2 or 300,000 years is a fair amount of evolutionary time.
The transition to modern humans is one that people argue about. Did it happen subsequent to that time? Did it happen over a broad front? Did it happen to one group of individuals or one small tribe, who then became modern humans? I think it’s impossible to answer that question because it happened gradually. It didn’t happen all at once. And it happened as a result of mutations, as a result of migrations between human groups, the exchange of genes between groups, genetic recombination, which put these genes together in different combinations-all these things essentially led to modern humans as we know them. And that broad series of events is very different from the very simple-minded view that I think the science writers have proposed, which is that 200,000 years ago the Mitochondrial Eve underwent a mutation to turn her into a modern human and then she gave rise to all our genes. I mean that is just so false it’s unbelievable and yet you’ll find it touted out in all kinds of places including distinguished journals like Scientific American where I’ve seen it happen.
So, that is an idea that you really want to get out of everybody’s head. The evolution of humans is very complicated. It happened over a fairly wide range of different types, it happened over a long span of time. We now discovered it probably took seven million years or more. And the Mitochondrial Eve is only just a small part of that.
How did we arrive at such dates?
You’ve got to put a lot of things together to get a date. You can look at DNA alone, and that won’t tell you anything. You can say two individuals are diverged by so much. But unless you can put a clock on that divergence, then you’re got a problem.
You can put a clock on that divergence by looking at other groups of organisms where you know something about their fossil record. The best-known set of events that allows us to date things in the fossil record fairly accurately is the great Cretaceous/tertiary, or K/T, an extinction that wiped out the dinosaurs, after which various groups of mammals radiated. And if you look back then at several groups of mammals that you’re pretty sure don’t pre-date that time, you can say then that those groups probably began to diverge about 65 million years ago, and from that you can begin to fit pieces into place, because then you can use that molecular divergence as a yardstick to look at the molecular divergences and say among the great apes, or the divergence between the great apes and the Old World monkeys, or the divergence between the Old World primates and the New World monkeys. All these divergence times really come back to the 65 million-year-old date that we’re very confident of.
And the argument of just how good these numbers are is something that I think is going to go on for a long time. These numbers have always had big errors in them. And you can be reasonably confident of the rough divergence time of a lot of different animals and they all fit together in the sense that the sequence of events makes sense. Closely related animals tend to have closely related DNA. Distantly related animals tend to have distantly related DNA and that’s a very good correlation. But the exact number here is something that you’ve got to take with a grain of salt when you hear that the mitochondrial Eve lived 210,000 years ago. That’s 210,000 plus a bunch and minus a bunch, so there’s a big error on that number.
And for that number, the error is particularly great in the backward direction. That is to say, it might be 210,000 plus 50,000 but minus a 100,000 or 150,000 because the errors are not symmetrically distributed around that number for statistical reasons. So you’ve got then a great deal of uncertainty even on the recent dates, such uncertainty in fact that I think what may happen over the next few years — and I’ve made some arguments in the literature along these lines-what may happen over the next few years is that we’ll begin to move these dates back a little bit, that we’ll find that the Mitochondrial Eve really is a little bit older than we thought. And there may be other complicated things that will sort of tend to stretch out human history a little bit longer than we had thought.
Every time we find older fossils, every time we find fossils in unexpected places, we’re filling in that history, we’re extending the history back in time. When you think about it, a hundred and fifty years ago there was virtually no fossil record for the human species. Now there’s a pretty good fossil record. And as we learn more about it, we begin to realize that human characteristics developed over millions of years, evolved over millions of years, they didn’t all evolve at once. There wasn’t a sudden leap into full humanity. Human cultures evolved over much longer spans of time than people had thought. It’s now supposed that the characteristic of modern human culture goes back at least 300,000 years in Africa and probably longer than that. All these things together keep pushing the time back further and further so don’t take these numbers as gospel. The numbers are constantly changing as we revise our understanding of what’s going on.
How can we achieve the unification of morphological data with molecular?
Well, morphological data are very elastic. It’s very tough to tell much about evolution change just by looking at morphology. Morphological change can happen very quickly. That is to say that morphological change is the appearance of an animal or a plant. Morphological change can happen in a moment in the night in evolutionary terms. Genetic change takes longer.
The genetic changes that produce the morphological change might be fairly small. You can get a very small genetic change that can have a big effect on the organism’s morphology or conversely you can have a lot of genetic changes that have no effect on the organism’s morphology. So of the ten million or so genetic differences between humans and chimpanzees-I’m only guessing here, but I think it’s an educated guess — but I would guess perhaps no more than 200 or 300 are really important, that really separate humans from chimpanzees. Most of the others are just noise.
Genetic changes then tend to accumulate in a more clock-like way (because so many of them are noise) than morphological changes do. But morphological changes can happen very quickly. You’ve probably heard about the Limba, this fascinating tribe of people in South Africa who, it turns out, have a substantial genetic contribution from peoples of the Middle East, Jewish people in fact who apparently arrived in South Africa-a thousand, 2,000 years ago; nobody’s sure exactly when-bringing genes with them which have made a substantial contribution to the gene pool of the Lemba. But you look at the Lemba they don’t look the least bit Jewish. They look like southern Africans.
All those genes that have been put into the Lemba gene pool have had virtually no effect on their morphology, at least by this time. So genes can have a big effect on morphological characters, or genes can have a small effect on morphology, and it’s very tough to link these things up.
So morphological change — obviously the more different organisms are, probably the more likely it is that they are very different in evolutionary terms, but sometimes you have organisms that look very similar but in fact, are genetically very different. Morphology can fool you. Genes are less likely to fool you. You’re a little happier with the genes than you are with morphology.
If you go to Australia, you’ll find there are Australian flying squirrels, there are Australian moles that look just like the flying squirrels and the moles of North America but they’re not. They’re genetically very different. But morphologically they’re very similar. They’ve converged on these very similar morphologies independently in different parts of the world. So I like genes rather than morphological data for keeping track of evolution.
Can you point to other examples of molecules used as time devices?
There are a lot of genes known now. The Human Genome Project has opened up a wonderful opportunity for us because we can now look at a lot of different genes in detail. Once you know the sequence of a gene in humans, you can quickly track that gene down in other animals so you can look to see what that gene is like in chimpanzees, you can look to see what it’s like in rhesus monkeys, and so on. So you can tell a lot about the relationship between genes once you know all the genes that an organism has. And we have most of the human genes, not all of them, but most of them. So we’re in pretty good shape here from looking at these genes.
As a consequence, people are now looking like crazy at a variety of different genes that go back beyond the Mitochondrial Eve. Remember I said that there were some human genes that began to diverge further back. And this is the kind of thing, the kind of data that Alan Templeton used to get some indication that there was some genetic exchange between Africa and Asia before the time of the Mitochondrial Eve, which I find very exciting, I don’t know if this will hold up but I think it’s a very, very interesting statistical approach to this question, and as more data come in, my guess is that his conclusion will be reinforced, because the more we know about these other genes — these are the genes on nuclear chromosomes — the more we know about these genes the more we’ll understand about our own evolution and it’s going to be really, really exciting I think.
As to what these genes do, some of them we know something about; some of them we really don’t know very much about. But we’ll learn a lot over the next few decades. You’re going to see a lot more understanding of the evolutionary history of our species.
Can you touch on the coalescent theory?
Coalescent theory is a mathematical way of looking at something like the Mitochondrial Eve. You can apply it to any genes, really, but it’s a little more complicated if the genes are recombined and so on. The mitochondrial chromosomes are nice because they give you a nice, statistically approachable way of getting at the question of when there was a common ancestor to a particular gene or a chromosome.
If you think about coalescent theory, what it does essentially is turn time on its head. You’re now traveling backward in time instead of forwards in time, and you’re going back, generation by generation.
Suppose you look at a group of people who have, say, ten different mitochondrial chromosomes among them. Then you go back one generation. It’s a reasonable chance that that there may be, as it were, a reduction in the number of lineages if you go back just one or two generations, simply because you’ve got ten different lineages, any two of which could fuse with each other, so to speak, to make an ancestral lineage.
Coalescent theory is the mathematical theory that underlies this question of the Mitochondrial Eve, and all other situations where you’re trying to trace genes back to their common ancestors.
If you start with a lot of genes at the present time, different genes-that is to say different versions of the same gene shared by different people — and then you go back generation by generation, these genes begin to fuse together, and they fuse together very quickly at first because there are lots of different ways two genes could have a common ancestor.
But if you go further back in time, the chances of such fusions get to be less and less because now there were fewer and fewer lineages. So you must go further and further back, further back, until finally, you end up with only one lineage, and it’s at that point that everything is coalesced. All these genes have coalesced together into a single ancestral gene.
Coalescent theory is hideously complicated and you’ve got to make all kinds of assumptions about how things work, but in essence, that’s essentially how it works. It’s a way of mathematically quantifying the question of divergence among genes over time, how genes divergent over time and long it takes you to get back to a common ancestor.
What does population size tell us about evolution?
The size of the human population is interesting, because until recently it was very small. It exploded recently. Over the last few hundred years, it’s simply gone through the roof. So we think of course of humans now as having an enormous population, and there can’t be very much more evolution going on because the general feeling among many people is that evolution is more likely to happen in small populations than in large ones.
The reason evolution might happen in small populations rather than large ones is for various reasons. First of all, chance may play a big role in a small population. You may lose certain genes, you may increase other genes in frequency in a small population. That’s more likely to happen than in a large one. Small populations are more likely to be present in rapidly changing environments, so if the environment is changing quickly and putting new selective pressures on a population, it’s likely that the population will be small because it’s surviving this rapidly changing environment.
Big populations tend to inhabit fairly constant environments. You know if you look at sardines in the sea, or something like that, obviously there’s a very large population of sardines and-well, at least there was before we began to fish them-and that very large population of sardines is living in a relatively constant environment, perhaps one that has not changed over long period of time. Rapidly changing groups of organisms, it is thought, are more likely to be small and more likely to inhabit rapidly changing environments.
Now there are lots of arguments against that. Ah. Some people claim (and in fact, I’m inclined to sympathize with them) that large populations can evolve too. They can evolve because they may become subdivided into smaller groups, or they can evolve because the large population has a wealth of genetic variability, which can be sorted out if the environment changes. So in a large population, in which the environment changes, you can actually have substantial genetic change.
There are microorganisms in the ocean-for example Foraminifera, and other organisms — that are found in uncounted trillions and never go through reductions in population size, and yet they evolve. And you’ve got a pretty good record of their evolution because when they die they go to the bottom of the sea, and you can then follow them over time and see how they change. So here are huge populations that are nonetheless undergoing evolutionary change. So I think my own take on this is such: the population size can be important, but small populations aren’t an essential requisite for evolution. The human species at the moment is undergoing evolutionary change. We’re mixing our genes together in new combinations. People are meeting each other who would have never met each other before; children are being born who would have never have been born a generation or two ago because they are a mixture of different gene pools from different parts of the planet. Tiger Woods [who is an ethnic mix of African American and Thai] is an obvious example of that.
The changes that we’re going to see in the human species are going to be driven by this kind of mixing, even though our species is gigantic at the moment. It won’t always continue to be huge, and we’ll have to undergo a reduction in numbers at some point in the near future, or we’re all going to be in trouble. And during this brief span of time, even when our population is very large, I suspect that evolution hasn’t come to a stop.
How do you address the issue of race within the human population?
Well, “race” is, of course, a very loaded word. Biologists like to talk about “subspecies,” and if they can, they like to give them special names. If you have a species of bird that comes in different varieties-if they’re very clear cut and distinct varieties- then you might want to give them different subspecies’ names.
Human races are distinct. There’s no doubt about it. There is a huge amount of variation within each race, and distinct morphological difference between races. No doubt about that whatsoever.
Are these differences linked to big genetic differences? The answer is no. The majority of the genetic variation found in the human species is found within racial groups. Very little of that variation-5% or less-is found between racial groups, and that variation is not, as you know, such that blacks have one gene and whites have another gene, or something like that.
Now what happens is, you’ve got genes that appear at different frequencies in different racial groups. They may be at 20% frequency in one racial group; 60% frequency in another racial group — same genes, different frequency.
So the differences then between racial groups have to do primarily with a rather small number of genes that are involved in skin color, hair color, and shape, some morphological differences, perhaps facial differences-something like that. The enormous majority of the genes are essentially the same among different humans. So when we look, then, at these differences and say, oh, wow, you know, this person is one race or another race and then all our prejudices come to bear on this, and so on, we’re being fooled by morphological differences that really have very little genetic basis.
How closely are modern humans related today?
If you pick two humans at random from two places on the planet, they really differ by only a tiny fraction of 1% of their DNA. And most of those differences, as I say, are noise.
So humans, even though they may be of different racial groupings, are nonetheless extremely closely related to each other-more closely related than most animals are. We have less genetic variability in our gene pool than our close relatives the chimpanzees do, for example. Chimpanzees probably have two or three times as much genetic variation in their gene pool as we have in ours, even though chimpanzees have been much more restricted over time. They’ve been confined to certain parts of Africa. They are not spread through the Old World. They, nonetheless have more genetic variation than we do.
It has been suggested that the small amount of variation that we carry, which by the way also comes back to this race business, that we make these enormous distinctions based on this tiny, tiny fraction of our DNA, which is less than the differences that you’ll find between two distinct subspecies, let’s say, of birds. So we’re talking here about tiny, tiny little differences, huge amounts of fuss about tiny little differences.
If we look at humans, in general, we find that they’re very closely related. If we look at chimpanzees, in general, we find that there is a distinctly greater degree of separation among chimpanzees, even among chimpanzees of the same group. They are genetically more different from each other than two humans drawn from a particular human group.
Is this because of the age of the species?
The age of the species is undoubtedly a factor. The chimpanzees, as a species, go back further in time than does Homo sapiens. You’ll find that the Mitochondrial Eve goes back not just a couple of hundred thousand years but perhaps several hundred thousand, perhaps close to a million years. But the chimpanzees have had more time perhaps to accumulate genetic variation. In the past, they may not have undergone reductions in population size as severe as some of the reductions in population size that humans have undergone. But I don’t know. I really don’t know. People are arguing both ways on this. The mitochondrial data suggested humans may have undergone strong reductions in population size. There may have been times when humans became very, very few in number.
But there are some nuclear genes that suggest: no, that may not have happened. And my guess is that reductions in population size happened in the human species in the past, but they affected different genes differently. There are some genes that are more likely to get through such a reduction in size with all their variability intact. Other genes are more likely to lose their variability, perhaps because they’re less strongly selected, and so we get a mixture. It depends on what you look at. Mitochondrial DNA seems to be strong evidence for strong reductions in population size.
The HLA complex, which has to do with the ability to respond to disease organisms, this complex is an extremely polymorphic one. Look at that, and you don’t see much of evidence for a reduction in population size.
And why this disparity? I think it has to do with the history of the genes themselves. It’s complicated stuff, but it does suggest that lots of interesting things happened in our past and different genes give us a different take on that history. We have to try to disentangle all these possible scenarios.
Obviously, if we went through a reduction in population size, it would have affected all our genes, but I think it affected some genes more than others.
Is what you’re talking about referred to as a “genetic bottleneck”?
Well, genetic bottlenecks have to do with the question of how much genetic variability there might be in a population. If populations undergo strong reductions, extreme reductions in size, as a result of a changing environment, for example, as a result of diseases, or as a result of running out of resources, or as a result of migrating into a new area, a “genetic bottleneck” may occur when that population size becomes very small.
Native Americans, for example, came across the Bering Strait apparently 13,000 years ago and rapidly populated North and South America. This was a very strong bottleneck, because very few people got across to North America, and they left behind the great majority of the gene pool that they came from, so they brought with them a very small sub-sample of those genes. That kind of evolutionary event is one that can have quite dramatic consequences. The people who arrived here, for example, were all of Blood Type O, or at least if they had the other blood types, they lost them quickly. So all Native Americans, then, of both North and South America, who haven’t crossed with other groups of people, have Blood Type O and, as you know, in the rest of the world there are four blood types: O, A, B, and AB and this is quite unusual, because you don’t find other human groups that have only this one type.
They also lost other kinds of genetic variabilities as a result of this bottleneck, so this is a classic example of the bottleneck in the human history. You find bottlenecks in other organisms as well, and they can have profound effects on the course of evolution.
In what ways do phylogenic trees help us understand evolution?
We’ve come up with some tricks for looking at phylogenic information, that is to say, the information that tells you about evolutionary history and sieving out the noise from the signals. And if you do that you can sometimes get a clearer signal, especially if it’s a very noisy set of data. You can get a clearer signal by doing this.
And we’ve done that fairly successfully with human mitochondrial DNA, and with one or two other systems that have allowed us to get a clearer idea of the sequence of events that took place during the process of evolution.I’ve also been interested lately in this question of mitochondrial DNA-and this is highly speculative-whether there’s any evidence that mitochondrial DNA in humans might occasionally recombine. Generally speaking, as I said, the male’s mitochondrial DNA gets lost at the time of fertilization so the sperm mitochondrial DNA usually gets kicked out.
But in some other mammals, occasionally mitochondrial chromosomes do survive and recombine, so you do get some recombination that happens, and the question is: Does this occasionally happen in humans? And I’ve been groping towards statistical methods for looking to see if there are pieces of mitochondrial DNA that are very old, that might go back before the time of the Mitochondrial Eve. Are there bits of mitochondrial DNA that preserve genetic variability that is older than that of the Mitochondrial Eve? That would be fun, and I’ve got one or two candidate segments of DNA, but I don’t know whether that’s going to hold up. I’m just experimenting with it a bit to see whether I can get some idea of whether it might be possible to push the mitochondrial chromosome a little bit further back in time.
What types of methods do you use in these experiments?
One uses computers to go through piece by piece, looking at building trees, looking at divergences of subsets of the chromosomes to see whether you can find little bits of the chromosomes that have more divergence than they should. And there are some extreme examples of divergence. The trouble is that it’s tough to decide whether this is just a chance event or whether it’s real, and that’s what I’m currently wrestling with at the moment.
I think one of the things you learn about biology is that there are always exceptions to the rule. So when everyone says mitochondrial chromosomes never recombine, well, you never say never. You’re never sure that, every once in a while, there might be a recombination event that could bring an older piece of mitochondrial chromosome in, and that would be interesting, because it would come back to the question of earlier mixings of genes the kind that Alan Templeton has been looking at, looking at the nuclear genes. It would be fun to see whether one could find some trace of that in the mitochondrial chromosomes as well. But that’s just a little project I’ve got going on, on the back burner, and we’ll see how that develops.
Are humans still evolving?
I’ve taken a contrarian’s view on this, I think. The great majority of biologists would say, no, we’ve stopped evolving. Why should we evolve? We don’t die of diseases anymore. That’s not true, but diseases are less of a factor, at least in the Western world, than they were a century or two ago. People have enough to eat, at least they do in the Western world. People can have in theory as many children as they want so the numbers of children that a person can have is not as limited as it was, mortality from all sorts of other causes is much less than it used to be, so evolution should have come to a stop.
But I don’t think that’s necessarily true at all. It’s certainly true that we’re not being as strongly selected for disease resistance as we were a few generations ago but there are other diseases coming up. AIDS is an obvious example, and other diseases on the horizon that might bring back some very, very strong selection in that regard so I don’t think we’re out of the woods yet on diseases. The majority of humans are relatively well fed at the moment, but there’s an enormous minority who are not and so starvation is still a very severe factor.
But I think that the primary factors, the primary pressures, that are acting on the human species at the moment are pressures that act on our behaviors, pressures that act on our mental-I don’t want to say capabilities-but our mental attitudes. For example, it’s now possible for the first time to be able to choose whether or not they want to have children; lots of people are choosing not to have children or they’re choosing to adopt children or do other sorts of ways of having children that are not genetically related to them. That’s something brand new. That kind of choice is one that people didn’t have and the presumption that everybody is capable now of reproducing I think falls down because there are loads and loads of examples of people who don’t reproduce, not because they’re sick, not because they’re starving, but because they choose not to.
And that, as I say, is something brand new. What kind of evolutionary pressure does this have? What kinds of people are choosing not to have children? We don’t know. But it’s probably having quite a substantial effect on our gene pool because that kind of choice is very widespread.
The ability of people to handle the onslaught of information and stimuli in our environment also varies from individual to another and that’s going to have an impact as well. How well can you handle the environment? How well can you exploit the environment? The environment is changing all the time. Our environment is changing with blinding speed, and the ability of some people to find a niche, the ability of some people to acquire resources varies enormously from one individual to another. Is this a selective pressure? Yes, I think it is. One doesn’t have terribly hard data on this, but the feeling I get is that we are subject to intellectual and mental pressures of the sort that our ancestors never came up against, and that’s got to be having an effect on who reproduces and who doesn’t.
What is the main point you want this audience to understand?
We talked about the Mitochondrial Eve and how widely misunderstood the poor lady was-and still is-and I think it’s important to get that straight. And I think it’s even more important to look at our evolution as an ongoing process, to look at it as a process that has taken a very long time, millions of years, during which time many different things had to happen. It’s not a case of suddenly somebody appearing who was suddenly fully human. I’m reminded of a cartoon. It shows a caveman and woman standing there on all fours in front of their cave, and the kid’s standing up like this. And the father is saying, “No, no, junior. Down on all fours like your mother and me.”
The possibility that people suddenly turn into a fully modern human being, bang, like that is something that is terribly simple-minded and utterly wrong. It was a gradual process. I think people have been brainwashed by the late Stephen J. Gould, who suggested that evolution goes in fits and starts, and you go through long periods where nothing much happens and all of a sudden there’s a sudden change. That’s not the case in human history.
If you look at the fossil record, you don’t see that stop and start stuff. You do see periods of more rapid change, periods of less rapid change, but starting millions of years ago people began to acquire upright posture, they began to acquire more mobile and sensitive hands, they began to acquire bigger brains, they began to acquire the capabilities of language, I think much earlier than people suspect. They began to do a lot of different things that we think of as being quintessentially human, but it was through a series of gradual changes.
And that’s I think a very important point to make. Evolution didn’t all happen at once, and I think it’s continuing. I don’t know where we’re evolving. I don’t know what we’re going to evolve into. My guess is we’re going to remain extremely divergent, and perhaps become even more so as time goes on, and that, in the next generation or two, we’re going to begin to take our own evolution in hand. We’re going to begin changing our own genes, and that’s going to be very interesting to see what happens there. I don’t quite know what’s going to happen.