Welcome to the 7th in this
series of evolution lectures. I'm Mike Cusanovich, director of
Arizona Research Laboratories. And I'm standing in for our
Dean of Science, Joaquin Ruiz, tonight. He's at another event. And it's a real pleasure for me
to introduce tonight's speaker, Dr. Michael Hammer. Mike is a small college guy
from Lake Forest College. Did his PhD At the University
of California, Berkeley, went on to post-doc
at Princeton, and another post-doc at
Harvard, and then, fortunately, came to Arizona,
in 1991, to work in Arizona Research Laboratories
as a research scientist. During his stay here,
he's evolved his research to the point that he's now one
of the world's leading experts on human origins,
traced with DNA, and has made tremendous
contributions. One way to look at this,
he has appointments in Arizona Research Laboratories
in ecology and evolutionary biology. But he also-- and I
don't know why it's not on this slide-- has an
appointment in the Department of Anthropology. And that ties together his work,
and the impact of his work, very nicely. I won't read you the title. You can read it. And ask Dr. Hammer to step
up, here, and give his talk. Thank you. Well, it's really a
pleasure to be here, and to have the
opportunity to address our campus, and our community,
on this topic of human origins, using DNA to trace our origins. I've chosen to highlight
three different themes in my talk, tonight. The first one is
our place in nature, and the second one
is the evolution of the traits that
make us human-- trying to track both of
those, not only genealogically but in history, as well. These are issues that
Darwin addressed directly. And then, the
third theme will be something that's related but
something that Darwin didn't address, because
this is something that has been debated most
intensely in the last couple of decades. It's a topic that deals
with the origin, how our species originated--
the modern human species. In order to do the work that I
do, and to address this issue, in general, genetics
isn't enough. It can't stand up on its own. We need many
different disciplines to work on this together,
to give us the full picture. Paleontologists are involved
in this topic as well. They study fossils to infer
the morphological changes that have occurred over
evolutionary time. Archaeologists who study
material culture-- stones, stone tool kits-- to trace
the history of our species, to infer the
behavioral changes that have occurred through time. And then, of course,
genetics-- the area that I'm involved in-- using
both protein work and DNA work to tune infer our
genealogical history. And one of the points I'm going
to make in the talk tonight is that the genealogical
history for different parts of our genome can tell
us different things about our history. And that's one of the
challenges that we face in trying to put
together a story-- a full story--
about our history. The history of the
field of genetics, as applied to
anthropology, goes back to the early 1900s in work that
was done at the protein level, and up through the 1960s. And I'll talk a little bit
about some of the work that's been done with protein. And then, the transition
into DNA work, in the 70s through the 90s, and
studying individual genes and the sequences
of those genes. And then, in the last few
years, having entire genome sequenced that we
have at our disposal to make inferences about. Now, I'm going to try and
limit the technical information as much as possible, which
is a challenge in itself. But I will probably convey
a lot of the ideas to you through this drawing--
these tree drawings. So on the left,
you can see a tree that may be a tree
that was developed by anatomists, comparing
the anatomy of humans and great apes and
inferring the relationships. That's the species tree. In the middle, I'm
trying to convey to you this timeline of
fossils as they've been discovered and dated. Paleontologists will
infer the taxonomic status of a particular
fossil by comparing it with other fossils, its time
depth in the fossil record, and make inferences that
almost look like a tree. You can see these
branches that I've shattered underneath these
timelines of fossils. And then, on the right, is
a tree that is a gene tree. It's not a species
tree, but it's a tree that reflects
the genealogical history of a particular
region of the genome. And the time frame for
that genealogical history can come from the
number of mutations that we see in the DNA, using
some kind of a molecular clock approach to infer the
time depth of the tree. Now, let's turn to what Darwin
said about human evolution. We can summarize
it in one sentence. In his Origin of
Species, from 1859, "Light will be thrown on the
origin of man and his history." That's all he said in
The Origin of Species. And if we look a little
further in the literature, we find that he wrote to
his friend Alfred Russell Wallace, a couple of
years before he published The Origin of Species,
in 1857, when asked, would he address this
issue of human evolution? And what he said was, "I think
I shall avoid the whole subject, as so surrounded
with prejudices, though I fully admit that
it is the highest and most interesting problem
for the naturalist." But his ally and bulldog, Thomas
H. Huxley, just four years after the publication of
The Origin of Species, published his own book called
evidence as to man's place in nature. And he wasn't shy about tackling
this issue about human origins and applying evolutionary
theory to human origins. What he did was, he did an
extensive comparative analysis of human and ape
anatomy, embryology, and ethology--
behavior-- as well as looked at the very,
very few fossils that were known at the
time, and concluded that humans have a close
evolutionary relationship with the great apes, in
particular the African apes. So this was striking
for many reasons. At the time, there
were many out there who didn't believe that humans
had any relationship at all to the rest of the
biological world, number one. But then, to claim that humans
were related to African apes, as opposed to the
orangutan Asian ape, was quite a striking
statement, a bold statement. But perhaps the
biggest impact would be in a philosophical sense. Humans now were seen as
part of nature and not apart from nature. In fact, the
Darwinian revolution followed, by a
couple of centuries, another revolution
in Western philosophy stirred up by
Copernicus, who gave us the heliocentric
universe, disposing of the geocentric
universe where everything circled around the earth. Earth now circled
around the sun, and was just one planet
of many in the universe. It was no longer the
center of universe. And similarly,
Darwinian revolution took man up from
position out of nature into a position in nature,
and made the naturalistic view of man. But still, , the
human, in either case, still remained at the
pinnacle of God's works. And so, these revolutions
are in the context of these other kinds
of thought processes of natural philosophers
at the time. Still, Huxley made
a statement that gives us a picture of
the kind of tension that existed between the
continuity of placing man in nature and the
discontinuity of man from the rest of nature. In this quote, "No one is
more strongly convinced than I am of the vastness
of the gulf between man and the brutes, for he alone
possesses the marvelous endowment of intelligible
and rational speech, and stands raised upon
it as on a mountain top, far above the level
of his humble fellows, and transfigured from
his grosser nature by reflecting, here
in there, a ray from the infinite
source of truth." So what I'd like to
talk about tonight is a bit about the tension
that's shown in the statement. What is the
relationship between man and the rest of the
biological reality, and follow the history
of that, and see what DNA and
molecular approaches have done to help us
understand that relationship. And in the first two themes
that I'm going to be developing, the first is what
is the relationship of man to the great apes? And I use the word "man" in the
18th- and 19th-century sense. Another way of
putting that question is, how far back in time
did humans and great apes share a common ancestor? That's them number one. Theme number two is also
something that has been debated greatly in the last century,
and that is the question of "human-ness." The traits that
make us so special, and so different from the animal
world, when did those evolve? And when we answer
that kind of question, we think about all
the changes that occurred on the lineage
leading specifically to modern humans--
this lineage, here. And I've shown some
fossils that represent extinct forms of
humans, or pre-humans, on the lineage leading
to modern forms. And I will refer to
all of the creatures on this branch as hominins. Now, these two
themes, in practice, are deeply intertwined. Because, in order determine
what makes us special, we need to know who to
compare ourselves with. So what is the
history of this idea of establishing the link between
humans and the great apes? As I just mentioned,
Darwin and Huxley both, through their
analysis, reasoned that humans were closely
related to the African apes. Whereas the view seemed to
shift, after 1920 or so, up until 1960. The view shifted
back to one where humans were much more distantly
related to the great apes. In fact, it was seen that
great apes-- the African apes and the orangutan-- were closely
related, and either of those being more related to each
other than any to humans-- humans being very distinct. And one version of
that, this is work that was written in the
1920s, as representative of the kind of things
that were being said in those days--
worked by Sir Arthur Keith. He showed this family tree,
here, of the great ape lineage, here, the human
lineage, and seeing how far back in time
they coalesced back to a common ancestor
in the Oligocene-- which, today, we know to be
about 30 million years back in time. Along with this view of the
ancient split between humans and the great apes, was the
view that human populations, themselves, traced
back very far in time, so that the different
racial groups were very old. And these were very consistent
with the racial views of the time-- that
the white race had reached ascendancy more
recently than these other races around the world. This was a common
view at the time. So perhaps the most
important fossil support for this ancient
divergent hypothesis was not that old in time. It was a fossil
called Ramapithecus, that had been
discovered in the 1920s, and rediscovered
by Elwyn Simons. Ramapithecus is an
ape-like creature that lived in Eurasia
about 15 million years ago, and appeared to be anatomically
related to the hominid lineage, according to Simons. And based on these
similarities, he suggested that this lineage had
the Ramapithecus, right here, on the lineage,
which would support this very ancient
divergence between humans and the great apes. Well, let's now look at
what the molecular field has done for us in 1962 the
term molecular anthropology was termed coined by Emile
Zuckerkandl and Linus Pauling, who were
the first to suggest that one could use molecular
approaches to infer evolutionary history. By comparing the sequences
of proteins extracted from different
organisms, one could then infer the evolutionary
relationships of those organisms. This launched a new field called
molecular anthropology, which was really christened by
Morris Goodman in 1963, and then Sarich and
Wilson, in 1967, who made immunological
comparisons among the proteins of African apes,
orangutans, and humans, and showed that, yes, humans
were more like African apes than either was to orangutans. Goodman's analysis
was qualitative. Sarich and Wilson's
analysis was quantitative. And this shows you the
result. Darwin was right. Huxley was right. According to the
molecular approach, humans share a relationship
with African apes that only goes back 5 million years. And this was the
Sarich and Wilson result-- the quantitative
result-- suggesting an incredibly recent
divergence between humans and the great apes. In fact, this
conclusion was heretical for a number of years,
and wasn't fully accepted by the
anthropological community, until additional
fossils had been found, which gave us a better view
of where Ramapithecus fit onto the tree of the hominoids. In fact, Ramapithecus now is
classified as a fossil ancestor of the orangutan. And so, all of the
picture makes sense. And in this case,
the molecular studies led the way in seeing
the right answer, if we ignore what had been
said by Huxley and Darwin 100 some years before that. But notice, on this
tree on the right, that we have basically
a three-way split, or a trichotomy. How can we resolve
this trichotomy? There are a number of possible
ways it could be resolved. It could be a true trichotomy. It could be that these
three species actually diverged so close in time
that, essentially, they are all equally related to one another. Or you could have any of these
other permutations, where gorillas and chimps are more
closely related to each other, or one of them related
to humans more so. In order to resolve
this, a great deal of genetic information
was necessary. Because it is, actually, a very
small period of time in which these three species
separated from one another. And in order to
solve this problem, we require the new
technology of DNA. And there were two early
pioneers in this regard. Sibley and Ahlquist, who
explored DNA kinetics and how, by hybridizing the
genomes of different species, one could determine
their relationships. And then, there was the
work by Morris Goodman, by looking directly at
the DNA sequence level. Looking at enough genes,
enough sequence, lined up from chimps,
gorillas, and humans, one could infer who was more
closely related to the other. In fact, when this
work was applied, the answer came out in
both cases-- for Goodman and for Sibley and
Ahlquist-- to show that humans were more closely
related to chimpanzees than either was to gorilla. In fact, these studies
were right on the mark in showing that humans and
chimps share about 98.8% percent of their DNA sequences. So that's fairly striking. So if we kind of, now,
look back at the history of the idea of man's
place in nature, we can see that it's
really characterized by a series of
demotions, starting with humans beings having
a special creation, to humans having a special
branch on the tree of primates, to humans being one
of many branches on the tree of primates,
to humans and chimps being part of the same genus, almost. So this is striking
information, and had striking consequences
for how we view ourselves and our place in nature. In fact, because now we
can look in the genome to see what makes us special,
we have a special trick we can use. We can look at the
chimp genome to see where the differences are,
and what differences may have arisen that do make us special. Now, if we move to
theme number two, trying to track how
far back in time these special traits may have
evolved that make us human. Darwin had a view
about this as well. Basically, Darwin figured
the first steps on the way to the human lineage,
when apes first budded off into this group that
eventually became humans, that brains led the way. He reasoned that
a smarter ape was the thing that would eventually
get us to being humans. The other view was that
walking led the way-- that standing upright
would be the first step in the early process
of becoming human. In fact, Darwin had a good
reason to put forward his idea. He reasoned that, in The Descent
of Man, those characters that make us human he identified as
intelligence, manual dexterity, technology, and uprightness. And he argued that
an ape endowed with minor amounts
of intelligence, or any of these other
characteristics, would surely give that ape
an advantage over other apes. And a forebear endowed
with these qualities, then, would just inevitably
become human through the power of
natural selection. In other words Darwin
thought that hominin origins equaled human origins. For those of you
who don't recognize, this is the monolith in 2001. Well, Darwin didn't have
fossils at his disposal to test his hypothesis. So it wasn't until
many years later, in the 1940s, '50s,
and '60s, when we had a huge number of
fossil discoveries, that allowed us to piece together
the history of the origin of these different forms
that eventually became modern humans. And so, this slide
shows you a summary of the current view from
the fossil evidence, with some of the key
players on the side. You have Homo erectus, Homo
ergaster, and Homo habilis, shown here. These are all part of the genus
Homo, which is shown in blue. And then you have
Paranthropus boisei, robustus, and aethiopicus, which
are shown over here. They're later bipedal apes. And the reason I contrast
them is because, you can see, they lived, actually,
at the same time. Darwin also had the
idea that humans evolved along a single lineage. Well, with this number of
new fossil discoveries, it became apparent that there
were multiple species that co-existed at the same time. And you can see
that, boisei, here, with the large sagittal ridge
on his head, and you can see, over here, erectus, could
not be characterized as the same species. But more importantly,
what we can see from this ordering
of characteristics is that the earliest
hominids, leading up to the australopithecines--
Lucy is the most famous of the australopithecines--
essentially, were small-brained
creatures with large teeth, and clearly proved
Darwin to be wrong. These earliest members
of the hominid lineage, in fact, could be seen
as bipedal "apes"-- with the quotation
marks around "apes," since we're talking about
the hominid lineage, we're no longer apes. But they looked a lot like apes,
but they were able to walk. These early bipedal
apes eventually gave rise to more
robust forms, called Paranthropus, and more
gracile forms, the genus Homo. Eventually, the genus
Homo led to Homo sapiens, here at the top. And you can see how recent in
time our species, Homo sapiens, emerges in the scheme
of hominid evolution. So we can say, by looking
at the fossil record, that we no longer
would consider Darwin to be right in this count. Hominid origins are not
equivalent to human origins. And we must think, now,
of the early evolution of our specialness being one of
being upright, where the larger brains came later. Most of us, I think,
would say that part of what makes us special are
the cognitive abilities that must relate somehow
to our larger brains. But we're not quite there
yet, because this slide is showing you the
encephalization quotient, which is a way of giving
you the relative brain size to body weight
on the y-axis, and the time scale
on the x-axis. You can see that, if we
compare ourselves to chimps, we have a larger brain relative
to body weight, at the top, and then, the various
fossil species that I talked about
earlier in the middle. And you can see that the
so-called bipedal apes have a slight increased brain
size over that in chimps, intelligent omnivores. Those early members
of the genus Homo had a slightly larger
brain size, again. But neither reaches the brain
sizes that we have at the top. So in order to get to the
characteristics that really make us human, we have to go on
to the next stage of evolution and talk about the transition
to anatomically modern forms. Also the tool kits of
the various species that I'm talking about. It turns out that all of
the species I've discussed have been using basically
the same set of tools. About 2.5 million years
ago, the first stone tools are found in the archaeological
record, known as Oldowan tools, which eventually, about
1.7 million years ago, become a slightly more
complex grade of tools called Acheulean tools. Here you have
Acheulean tool kits. And you can see, basically,
what they look like. It's hard to tell a hammer
from a crescent wrench. So we're not there
yet, archaeologically, which is a reflection of
where we are cognitively, at some level. So in order to get into
that, and understand how we made the final
transition to the Homo sapiens-- the species
that we are-- I would like to bring up through
theme three of my talk tonight. How did we make the
transition to modern form? Homo sapien showing up
again, on the upper left. And now, it got some
different players, here, all in the genus Homo. And you can see, Homo
sapiens, or anatomically modern humans, shown
in the upper left, has a much larger
cranial capacity. It's pretty obvious when you
compare the relative sizes of the cranium versus the upper
and lower part of the cranium. I also want to point
out, again, that there are multiple species,
or taxonomic groups, living before Homo sapiens. And even after Homo
sapiens emerges, there are others that
coexist with Homo sapiens. Homo neanderthalensis,
which lived in Europe. Homo heidelbergensis, which
also lived in Africa and Europe. Homo erectus, which
lived in Asia. Homo erectus is thought
to have originated in Africa from a precursor that
may have been very similar. There's debate as to whether
there is Homo erectus in Africa, or Homo ergaster. I'm going to go with the
terminology of Homo ergaster giving rise to Homo
erectus in Asia. And then, this new find,
here, Homo floresiensis, which I'll point out in a minute. Now, this slide is
supposed to represent the very recent origin
of Homo sapiens, showing you the
geographical context. Notice, after Homo
sapiens originated, Homo sapiens rapidly
colonized the globe in the last 100,000 years. But Homo sapiens was
not the first species to migrate out of Africa. You can see that Homo erectus,
shortly after it emerged in Africa, migrated out and
colonized parts of Southeast Asia and East Asia. Now, this map shows
you the distribution of some of these fossil finds,
for Homo erectus in green, and the Neanderthal
range in blue. And what I wanted
to point out is, you have some of the earliest
Homo erectus or ergaster fossils in Africa, about
1.8 million years ago. And then, out here
in China, 1.2. Dmanisi, Georgia, 1.7
million years ago. And here, in Java,
1.7 million years ago. So shortly after the first
Homo erectus is known to exist, we find fossils widely dispersed
across the globe, at least the old world. And I also wanted to point
out that Neanderthals may have been around until
about 28,000 years ago, certainly coexisting with
modern humans in Europe. And in Asia, we have
erectus existing on Java till 25,000 years ago,
again, coexisting with moderns. And then this find of the
island of Flores in Indonesia, is quite interesting. These are people who
were no more than 3 feet tall, sometimes called
hobbits, that were probably related to Homo erectus--
descended from Homo erectus, and then underwent what
we call island dwarfism. And they look like
they have lived up until as recently
as 13,000 years ago. So one of the questions that's
so staring us in the face is, we are alone
as a species today, and yet, just as recently
as 10,000, 20,000, 30,000 years ago,
we shared the planet with other forms of humans. Why did this happen? Why are we alone today? That's an open
question, and a mystery, that I will try and
address, a little bit, through the rest of the talk. Now, I want to talk about a
couple of different models for the formation
of our species. There are two models that
have been hotly debated in the literature for
the last 20 years, both of them based strictly
on fossil evidence. The one here, on
the left, that is called multiregional
evolution suggests that, when Homo erectus
dispersed out of Africa, colonized Asia, from that
population, which remained fairly continuous across
that geographic space, gave rise to Homo sapiens
pretty much everywhere that it occurred. In this model,
there's no speciation. There's some local
differentiation among Homo erectus populations,
but when a novelty would arise, such as a gene that might
encode a larger brain, this gene would then
be free to migrate from one population
to the other, and perhaps with the advantage
of natural selection, spread throughout the
range of Homo erectus, so that Homo erectus made this
transition to the modern form, in concert, across the globe. This idea has its roots
going back to Darwin, in a sense, who believed
in gradual evolution of a single lineage. This model sees
Homo as one species. It makes the
predictions-- well, I'll talk about the
predictions in a minute. The other model is the
recent African origin model, which says that modern
humans originated in a single place in the
world, very recently-- Africa-- and from that African
place, came out of Africa, replacing all the other
non-modern forms that existed in Europe and in Asia. This model suggests that all
the genes that make us modern evolved in one geographic
location, somewhere in Africa. The model also specifies
the population was relatively small and isolated. And this model has its roots
in a different philosophy in evolutionary
genetics, that of one where you have
lots of speciation, the boundaries between
populations are hardening up, so to speak, genes are not as
permeable across populations because they're
beginning to speciate. It's a model of cladogenesis. Now, what are the predictions
these different models might make that
we could actually test using genetic data? Well, the multiregional
model, as I said, makes two predictions-- one
about place, one about time. I'm going to try and keep
it as simple as I can. In this model, you can see
multiregional evolution. These lineages all descend
back to Homo erectus time, and the transition
to modern is shown by this change from red
lineages to yellow lineages. But if you look at
the lineages today, we should be able to trace
them back very far in the past, and they should be able to trace
deep in Europe, deep in Africa, and deep in Asia. So we might say,
the lineage will trace many parts of the world. That's the place. The time-- they could be
going back, many of them, over 2 million years. For the recent African
replacement model, we have an African
population that contains all the
genetic variation of subsequent
descended populations. So all of the
lineages that we're going to trace that are
yellow, the modern lineages, are going to really trace
back to one place-- Africa. And they're going to trace back
to Africa much more recently than the lineages
would trace back to a common ancestor in the
multiregional evolution model. So we'd say, the
lineages trace to Africa in the more recent past. So now, I want to use these
predictions, time and place, the geological depth at
different parts of the genome, and ask, do the lineages
of different parts of the genome trace to one
place, and how far back in time do they trace, to see if we can
answer this question about how we emerged as our species. In order to do so, I
just need to tell you a couple of things
about the genome that we're going
to be looking at. There are essentially two
genomes in every cell. In almost every cell-- blood
cells don't have a nucleus. But most cells have a
nucleus and a cytoplasm. Inside the cytoplasm
of a cell, there's an organelle called
the mitochondria, which has to do with
producing energy for the cell. And it contains its own,
small circular genome. It's only 16,569 bases long. It's just over 16 kb in length. And it's inherited strictly
from mother to children. In the nucleus is the
rest of our genome. It's 3 billion base pairs. There's 23 different
pairs of chromosomes. The first 22 are
called autosomes. We get one autosome
from mom, one from dad. And then, the 23rd pair
is called sex chromosomes. You have an X chromosome and a
Y chromosome, if you're a male. And you have two X chromosomes
if you're a female. Now, this slide's a
bit tricky to see, but I've got four generations--
great-grandparents, grandparents, father and
mother, and a son at the bottom. And what I've shown here
is his mitochondrial DNA, this small, circular molecule,
here, his Y chromosome. And you can see that his Y
chromosome traces back to one male each generation-- to his
father, to this grandfather, and to this great-grandfather,
where his mitochondrial DNA traces back to his mother,
to this grandmother, and to this particular
great-grandmother. So none of the other
great-grandparents in this generation have
contributed their Y chromosome, or their mitochondrial
DNA, to this boy, here. However, if you look at an
autosomal pair-- I've just chosen a single pair for
the sake of simplicity-- you can see that this
patchwork of different colors and patterns represents
pieces of all autosomes that came from different
ancestors in the past. So you can see that this
piece of his autosome traces back to this grandmother, and
this piece to this grandfather, and so on. So what I'm trying
to say here is, because of the process
of recombination, pieces of the genome are
shuffled between chromosomes that are inherited
from father and mother. Each piece of the
autosome may trace back to a different ancestor, whereas
the Y traces back to one, the mitochondrial traces
back to one female ancestor in the past, all the way back
to a single common female ancestor-- that is,
the lucky mother of all of our mitochondrial
DNA, or the lucky father of all of our Y chromosomes. The same is not true
for the autosomes. And that's a point that
I can't emphasize enough, and I will try
and bring up again to tell you what this means
for our evolutionary past. So for technical reasons,
the first part of our genome that was studied, and
addressed the question of human evolution, was
the mitochondrial DNA, because it was isolated, it was
small, it was in the cytoplasm, we could isolate it
experimentally, and study it, back in the 1980s. And we were able to get
DNA sequence information. There was a landmark
study by Rebecca Cann and Alan Wilson at
Berkeley, in 1987, where they surveyed
mitochondrial DNA variation in many people from
Africa, Asia, and Europe. And what they inferred was
that all the mitochondrial DNA in these people they
looked at today traced back to a single woman
who lived in Africa. And I think it was the press,
and not the scientists, who dubbed that person
mitochondrial Eve. It gives us that strong
metaphor of tracing back to a single woman, in the
Garden of Eden-- which is a rather unfortunate
metaphor, in some regards, because the work did
not imply that there was only a single woman
living at the time. But there was just
one woman who was the ancestor of all
mitochondrial DNAs today. This work was
reproduced, in a sense, in the year 2000
by Ulf Gyllensten and Max Ingman in
Sweden, and colleagues. They looked at the entire
mitochondrial DNA genome. They sequenced the entire genome
in 53 different individuals, also from Africa,
Asia, and Europe. And I'm showing the
tree that they were able to infer from the data. And what you can see,
here, is that you have African lineages
on the bottom, and Eurasian
lineages on the top. And you can see that the
African lineages on the bottom are longer, deeper. And so, this reflects
part of the inference that they made that the
ancestor was in Africa. They found greater
African diversity, they found that the place
of the ancestor was Africa, and that they found the
time of the ancestor was recent-- only going
back about 170,000 years. So those are the
predictions of which model? The recent Africa
replacement model. Another very intriguing
piece of evidence comes from Svante Paabo
and his collaborators, their work on ancient DNA. They were able to
isolate a small amount of mitochondrial DNA
from Neanderthal fossils. And as you can imagine,
this is a tricky enterprise. Not only does the DNA
degrade over time, but all the people
who've handled the bones, or all the DNA that's floating
around in the laboratory, is just as easily studied
as this tiny, tiny amount of Neanderthal DNA,
unless you're very careful not to contaminate it. But they we're able
to show, conclusively, that the mitochondrial
DNA from their extractions of this Neanderthal bone were,
in fact, Neanderthal DNA. They did the experiment
multiple times, for multiple
Neanderthal individuals. And they showed in
this tree, over here, that the Neanderthals were
all very closely related to each other, and yet very
different from the huge number of sequences that had
been examined in humans at that point,
suggesting that there was no Neanderthal mitochondrial
contribution to the human gene pool. Again, this is a prediction of
the recent African replacement model, whereby African
ancestors make the transition to modern form, and then
spread out, replacing all the archaic forms. This is what I'm calling
the mitochondrial paradigm, because this work
was so powerful. It came at a time
before we had studied much the rest of the genome. It came at a time
when archaeologists and paleontologists were
making these debates based on fossil evidence, and they
weren't getting anywhere with their arguments. And this seemed to be the
first genetic evidence that came down, very
strongly, on the side of the recent African
replacement model. This is an image from the
cover of Newsweek, in 1988. They're flirting with this
idea, again, of African Eve-- mitochondrial Eve-- and the
search for Y chromosome Adam. And this diagram, on the
left, shows you, also taken from nature magazine, a
summary of the results that were published
by Cann et al in 1987. Now, it was clear to
many of us working in the field of genetics that
mitochondrial DNA is just one little tiny
part of the genome, and that we really
need to investigate many other parts of
the genome to see if we would find similar patterns. The most obvious next place
to look was the Y chromosome. And this reflects work
that my lab has done, and another lab at Stanford,
over the last decade or so, where we were pioneers in
looking for variation on the Y chromosome and
tracing variation, creating these genealogical
trees to see what it told us about human evolution. And what I'm going
to say is-- it's very simple-- the
pattern is almost identical to what had been
found for mitochondrial DNA. Number one, you can
see the tree has the African lineages
that are longer than the non-African lineages. You can see that African
diversity is greater. The place of origin is Africa. And the time to the most recent
common ancestor, for the Y, is even more recent than
for the mitochondrial DNA-- only going back, roughly,
about 100,000 years. Remember, the mitochondrial DNA
trace back about 170,000 years. So both systems are telling
us pretty much the same thing. But the fact that they traced
back to different times is quite interesting. It just highlights that each
part of the genome traces back to a different
ancestor, and that ancestor may have lived at a different
time or a different place. In this case, the place happens
to be the same-- Africa. And what we want to
know is, if we looked at many parts of the
genome, would they all trace back to ancestors
that live in Africa, consistent with this recent
African replacement model? Well, that work was done in the
middle '90s and the late '90s. And by this time,
new technology had emerged that allowed us to
examine greater portions of the genome more efficiently. And we started to
build up a lot of data on the autosomes and
the X chromosome. So the rest of the talk-- the
rest next section of the talk-- will be telling you something
about this huge body of work. So I'm going to try and
summarize it very briefly. First of all, if we look
at genetic diversity on the X and the
autosomes, compare that the level of diversity
between Africans non-Africans, you can see something
that's familiar to you. There's greater diversity
in African populations than in non-African
populations, for both autosomal and X-chromosomal data. There's about a 30%
or 40% reduction in non-African
diversity, perhaps hinting, again, at this
older population in Africa. Maybe our autosomal
and X diversity is reinforcing this
idea an African origin. Then there was a fellow
named Naoyuki Takahata, a Japanese fellow,
who wanted to do his own analysis of the nuclear
genome, which is much more difficult to do because of
the recombination obscuring the history of these
lineages over time. But what he was
able to do was find a number of studies
of the autosomes and the X chromosome--
independent regions, different gene
regions, that are shown in the column on the left. In the top two columns are
the Y and the mitochondria. It's just review for you to see
that they also trace to Africa. But many of the regions
on the X and the autosomes also traced to Africa. But notice that
not all of them do. Here is a region that
seems to trace back to an African ancestor. Here's another
region that traces back to an Asian ancestor. Here's one of the traces
to a European ancestor. I'm sorry. There are two
tracing back to Asia, and the rest are
tracing back to Africa. And there's one tracing
to Europe or Africa. So the general pattern is,
yes, a lot of variation in the nuclear genome
is tracing to Africa, but there are exceptions. And I don't want those
exceptions to get lost. I will talk about them,
explicitly, in a minute. But let me talk a little
bit now about some of the differences between
the mitochondrial and the Y chromosome results, and the
autosome and the X chromosome results. I've shown, again, this fossil
timeline of our ancestry, on the right. And on this side,
I'm showing you the time at which these
different parts of the genome traced to an ancestor. So I've already mentioned that
the Y and the mitochondria trace back to an
ancestor very recently, within the last 200,000 years. And I'm showing that here. Notice, for the X and
for the autosomes, the mean time for
many different studies traces these parts of the genome
back almost 1 million years or more. Sorry. Lost the slide for a second. So this is the average time
back to an ancestor on the X and the autosome--
almost a million years. And the bar-- the
vertical bar-- shows some of the range of estimates,
back to the ancestor, some of them going back to
almost 3 million years ago on the autosomes. So this is going back to time
when australopithecines were still walking around in Africa. But even the means are telling
us something much deeper in time than these
haploid-- or Y chromosome in mitochondrial--
regions are telling us. Just to highlight what some
of these patterns look like, this is works that's
been done in my lab in the last few
years, where we looked at a bunch of different
regions on the X chromosome. I'm showing the X chromosome
lying on its side, down here on the x-axis-- 16
different regions of the X chromosome. And I want to emphasize
that these regions are unrelated to each other. They are
independently-evolving regions because the process
of recombination. And so, when we
looked and estimated the time of the ancestor for
these 16 independent regions, and plotted them out
along chromosome, you could see they
varied quite a bit, from pieces of the
DNA that traced back to an ancestor
400,000 years ago, to some that traced as far
back as 2 million years ago. There's no particular
pattern when we look at them, as spread
out on the X chromosome as they are, but you
see this variability. If we plot those times, now,
not plotting them against the X chromosome, and plotting them
against just an axis of time-- going from 200,000 years
back to three million years-- you can see that the observed
values, that I just showed you on the previous slide, give you
a bimodal distribution of times back to the ancestor. This group here, and
this outlier group here. And these are the observed
times the common ancestor that I just described. This curve, here, represents
the expected time back to the common ancestor under
a recent African replacement model. So if we were able to simulate
a recent African replacement model, and you do this from
many different regions of the X chromosome, we'd expect most of
the regions on the X chromosome to trace back to an ancestor
about 600,000 years ago. But then, there's
this tail where we might expect some
to trace back further in time, under the same model. But if you notice, here,
this second little group in this bimodal distribution,
on the tail of this expected curve, they're outliers. And they're not fitting
the model, exactly. So if we were to summarize
what this data were telling us, would be that, most
of the data are consistent with
this expected curve, the model of the recent
Africa replacement. But the recent African
replacement model can't explain all of the data. There are some outliers. And so, we wanted know
what these outliers were-- what was going on with them. And so, one of them--
I'm going to tell you one of the stories of
one of these outliers. This is a region on
the X chromosome, way out near the tip. It's a region of DNA that has no
particular function right now. It's a pseudogene. It once functioned as a
gene, but it experienced some knockout mutations. It no longer functions. So it's evolving in
a very neutral way. We don't expect it to be
affected by natural selection. And Dan Garrigan, in my lab,
was heading up this study. And here's Dan. I couldn't find another picture
of him other than the one riding his dog. But the pattern we saw,
on this particular region of the genome, was completely
different than what I was showing you for the
mitochondrial DNA and the Y chromosome. If you noticed,
before, there were Africans on one side of
the root of the tree, and everybody else on the right. Here, you see Asians on one
side, and Asians and everybody on the other side. There was greater diversity
in Asia, as opposed to Africa. The place of origin is Asia. And the time of the ancestor
is almost 2 million years ago. So we wanted to know
what this meant. Here's a way of portraying
that genealogy for that gene, right here, on the right,
against the fossil record again. And you can see that
time of the ancestor, back here at the
root of this tree, corresponds very
nicely to the time when Asian erectus and African
ergaster were splitting, diverging. And so, we think that
part of the genealogy of this particular
locus in the genome is reflecting erectus ancestry. So how would we have some
erectus ancestry in our genome? Well, this is a slide I've taken
from a paper first reporting the floresiensis finds. I thought it was very fitting,
because what they did was they showed how the finger
leading from Homo erectus to floresiensis,
bringing it right up, overlapping in time
with Homo sapiens. If we just imagine that as a
potential for interbreeding, then we could imagine
a scenario where, as modern humans
came out of Africa and colonized Asia-- Southeast
Asia-- found themselves face to face with these
archaic forms, there may have been
some interbreeding. And this, depending on
what level this occurred, could have allowed
certain of erectus genes to filter into the
human gene pool. So this was probably
the first evidence we had of something like this. There's more evidence
accruing as we speak. There are other studies
shown in the literature where we have these ancient
diverged lineages that don't fit the recent
Africa replacement model. They certainly don't
outnumber the number of loci that do fit the
model, but they are certainly something we need to pay
attention to in understanding what's going on. So because we have these
different patterns, and each region of the genome is
telling us a slightly different story, I like to think of
the genome as a mosaic-- as an evolutionary mosaic. If you look at one
region of the chromosome, it'll have a certain
genealogical pattern. Maybe it's tracing,
deep in time, to a certain part of the world. If you look at another region it
may have a completely different pattern. It may be tracing,
more recently, to a different
part of the world. Or it may be that that
particular region has undergone adaptive change-- it's
reflecting the process of natural selection. In any case, we can't
think of the genome strictly in terms of tracing
back to a single ancestor. We have to think of it
in this more complex way. It makes our analyses
more difficult, but I think it's
shedding some light on some very complex processes
that were going on at the time that Homo sapiens emerged. So how would I go
back, and say, what's the best model to explain what
we've observed with the data? I would say that neither of
the extreme models I presented can explain all of the data. But if we come up with some
kind of intermediate model, borrowing aspects of
those two extreme models, we might very well be able to
explain the patterns we see. So if we borrow the part of
the recent African replacement model, where populations
are isolated and tending to speciate, tending
to be different enough so they no longer
interbreed, but able to exchange some
genetic material-- gene flow between populations,
which we borrow from the multiregional
model-- we could explain, perhaps, the bulk of our
genome coming from one place-- Africa-- more
recently, with some leakage of these more divergent lineages
penetrating into our genome. And so, that is the
current view that, I think, explains all of the data best. So what it means is that for
the bulk of our genome tracing to Africa, recently,
we're mostly modern Africans,
wherever you live-- whether you live in Africa now,
or whether you've been in exile from Africa for a while. We are essentially modern
Africans, all of us. Except, there is some
part of our genome that may reflect something else. And I don't know
exactly what that is, but if it's a problem for
you, there's a solution. Maybe that's not so
surprising to some of the women in the
room who wondered why their husbands
were the way they were. And just to summarize,
we started out asking, how far back in time
did our special features as human evolve on the lineage? It's clear that
we've experienced a stepwise evolution
of our specialness. We started out as bipedal apes. We eventually got bigger brains. And we eventually became
modern, got bigger brains yet, and acquired the cognitive
abilities that we have. We don't see the appearance
of things like cave art until 35,000, 40,000 years ago. But we do see, in Africa,
the very early underpinnings of art, of culture, in
the archaeological record. And this is not a
very pretty slide. I just grabbed it off the
internet about two hours ago. I didn't have a chance
to make it look pretty. But we're tracing
some of the earliest, through the
archaeological record, things that you might qualify
as art-- painted beads, and things like that, that
trace back, in Africa, further than they trace back anywhere
else on any other continent. So just like the
genome-- the bulk of our genome--
tracing to Africa, it seems that the majority
of our cultural heritage also traces back to
Africa, but only going back on the order of 100,000
or 200,000 years. So the qualities
that make us special are very new in evolution. And I think we can
meditate on that, and I'll thank you,
take questions. Thank you, Dr. Hammer. In a book I recently read,
called The Journey of Man, the author uses what
are called DNA markers to trace the geographical
migration of man. Can you explain to me,
please, what a marker is? Sorry. I'm losing your question. The Journey of Man. Using DNA markers to
trace the journey of man. Can you explain that? Can I explain that? The journey of man,
and the markers that are used to study
that, essentially, are the Y chromosome and
the mitochondrial DNA-- those two markers
that I told you about first, that trace back
about 170,000 years ago, or 100,000 years
ago-- and reflect, very nicely, the colonization
of the world that occurred after modern
Homo sapiens emerged, about 200,000 years ago. So that part of our
journey is something only going back 100,000 years or so. And the mitochondrial
DNA and the Y chromosome are very well suited for
tracing that journey. But for tracing the journey
that was before that preceded that-- this entire
history that lies below that-- we must look
to the nuclear genome. Because that's the
only place we where not have the genealogical
depth to make inferences about ancient history. Doctor, I read a review
recently of a book called Demonic Males by
a professor at Berkeley. And he was highly
dismissive of the idea that we share 98% of our
genes with chimpanzees. Was he just being
a crank, or what? Demonic Males? Was that the title of the book? I highly recommend the book. I'm sorry. So the question was that
there's a book written called Demonic Males. Yes, but I'm concerned-- The author questioned the
relationship with chimpanzees? Yes. And he's a professor
at Berkeley. Well. He says that Sibley and
Ahlquist got it wrong. Well, I think that there's
too much evidence, now, from the whole genome. We've now sequenced the
entire chimpanzee genome, the entire human genome. So if he had any
problems with Sibley and Ahlquist's
experiments in 1984, or whatever, I think
that everything that's happened since then it has
verified their results. And I personally can speak
to aligning sequences from humans and chimps, and
counting the differences myself. So the data from
my lab don't lie. I don't know about
anybody else's. [INAUDIBLE] Back on the slide
that had the map, and where each of
the fossils are from, and it said that,
over in Indonesia, there were species
that might have existed as recently as
13,000 years ago, it showed in green and purple
the different locations of the fossils. And there was a
little bit of green up on the bottom of
the British Isles. What is that representative of? Yeah. Well, I don't know. What's that green doing
in the British Isles? There is some speculation
that Homo erectus got back into Africa and up into
Europe, and made it up as far as the British Isles. But there are also
other fossils that I haven't put on here--
Boxgrove, Homo antecessor, Homo heidelbergensis-- that
found their way into Spain and Western Europe. And they were transitional. They weren't modern. So I think maybe that
little patch of green might be the Brit's
version of archaic. [INAUDIBLE] We shouldn't debate
how far that green goes up the British Isles, though. I have a couple of
questions about taxonomy. When you say we're
modern Africans, no matter where we live, and no
matter the color of our skin, on the one hand. And yet, on the other hand, when
you are tracing the development from apes down to our line, you
had apes in quotation marks. And Sibley and Ahlquist didn't
just compare humans and chimps, but they compared
humans and gorillas, and gorillas and chimps. And of all the relationships,
the humans and chimps were the closest-- closer
than gorillas and chimps, or any other great apes--
which puts us squarely in the great ape group. So I'm curious why you
have the quotation marks. I didn't want to imply
that the hominid lineage itself was still an ape. We come from an ape stock. Well, but we still have 98%
plus agreement in the DNA. The taxonomic debate about
how you classify humans, now that we know that
we're so close to chimps, is not resolved. There are some
authors who would say that chimps should
be Homo troglodytes, or we should be Pan sapiens. And this was suggested by Jared
Diamond in his book called The Third Chimpanzee. That was my second question. Yeah. So I don't mean to be able to
resolve the taxonomic debate. I think the problem
is when you start looking at these different
regions of the genome, and each of them is telling us
something slightly different. I mean, on average, yes, we're
98.8% identical to chimp. So we should take that
for what it's worth, and the taxonomy will
eventually be sorted out. But it's not completely
sorted out right now. But you said that we're almost
in the same genus as chimps. Again, a taxonomic problem
that is complicated. I have a basic question
about the-- is the DNA that you're tracing coming
all from modern people? That's a very good question. Is the DNA that we're tracing
all from modern people? All of the work that I
reported to you tonight comes from
contemporary sampling, except the Neanderthal
bone mitochondrial DNA. There's very little
hope for us to be able to recover autosomal,
X chromosomal, Y chromosomal DNA from specimens that are
20,000 or 30,000 years old. So we're really
probably going to have to live with looking at
contemporary variation and tracing it back, rather than
looking directly at the past. For that, we've
got paleontologists and archaeologists who
look directly at the past. Their challenge is to know
who left descendants and who didn't. OK. Well then, going back in
time to the common ancestor, and looking forward,
what happened to all of the other DNA
that was in other people at that point in time? Well, that's an excellent
question as well. What happened to
the DNA lineages of all of the other ancestors? Well, you can think
of it like this. If we're tracking a
surname, for example, and there are 10
different people with 10 different surnames, and
they have children-- they have just two
children each-- they have a certain probability
of not having a son. And in those families
that don't have a son, one quarter
of the time they won't have a son, if
they're having two children. They will not have
their surname passed on to the next generation. And so, that surname
goes extinct. So it's a process of
extinction through a random who manages to get
their offspring in the next generation. For unilineal markers. Like the Y and the
mitochondria, it's a pretty simple story
of lineage extinction due to the lack of sons
or lack of daughters. The same thing can
be applied to others, it just takes a lot
longer when the lineages are jumping between different
ancestors in the past. Over here. Oh, hi. From your long look at
the journey up to now-- which, by the way, I thought
was very well summarized. Do you have any
speculative thoughts about the future evolution
of humans, generally? In brief, I understand. And specifically, I'm
interested in whether you see any indication
of, I don't know if you'd call it
sub-speciation the possibility of modern humans separating into
two or more different species. Well, that's a very
tempting question to answer. I sometimes look
around and wonder if we aren't already speciated. We say we should
learn from our past so we don't make the
same mistakes again. All we can do is try
and understand the past. And I don't know how predictive
that is in the future. There are a couple of
things that come to mind. One is that humans
are still evolving. There is some work
that's just been reported showing that effects of
natural selection on the genome are ongoing. So you might hear that, because
of medicine and other things, we've reduced the selective
pressure on humans that we're no longer evolving. But we are. And there are
enough changes that have gone on in the last
10,000 years that show that we are still evolving. I guess the other
thing to think about would be how humans
have become somewhat decoupled from our environment
because of our technology. [? I was ?] trying to trace the
origin, the ancientness, or how recent our specialness evolved. And I think one of the
things that makes us special is our technology. And for probably a fairly
long period of time, going back a few hundred
years, anyway-- a short time in evolutionary
sense, but-- we've develop technology
that essentially decouples our evolution
from our environment. However, I think with
next year's lecture series on climate change, we're going
to find out that we've probably created a new environment that
we may not be able to decouple ourselves from. So I think that's probably
something to think more about. How about round of
applause to Mike for an extraordinary lecture? Before you all leave, just
quickly, that next Tuesday, which will be the final lecture
of the lecture series, which will be on evolution of
disease, the HIV example, that lecture will be
at Centennial Hall. And all the lecturers
from the series will be there at the
end for a small panel discussion of the whole series. Thank you for coming.
