Homo sapiens - Carol Lee Lab

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Transcript Homo sapiens - Carol Lee Lab

"Light will be thrown
on the origin of man”
Charles Darwin
Human Evolution
(1) The Chimp-Human divide:
Hominins versus other Primates
(2) Adaptive Radiation of Hominin species
(3) The emergence of modern Homo
Human Evolution Resembles
a Messy Bush rather than a
continuous line
The line leading to us was not always from the most
“sophisticated” species at a given time; that is, the path
toward evolution of a larger brain was not a linear one.
For instance, Homo probably arose from the gracile
australopithecines rather than from the larger brained
strong robust ones
Among Homo, we descended from a lineage that had
smaller brains than the Neanderthals
When did Humans
First Homo:
~2.5 mya
First Australopithecine: 4-4.5 mya
Chimps-Humans diverged: ~5 mya
Adaptations to a Savanna
Climate Change?
Drier, more savanna, less
Lead to Adaptive Radiations of early
Phylogeny of Hominan Species
(Based on morphology)
Not certain exactly which
Australophithecine led to Homo
A rough cladogram based on dental
and skull characters
Fossil evidence of Hominin Lineages
Major African Fossil Sites
• We descended from the more gracile line
(not sure which, exactly)
• And not necessarily the larger brained
~2.4-2.8 mya
A. africanus
~3.0-3.9 mya
A. afarensis
A. afarensis
A. aethiopicus
~1.9-2.7 mya
A. boisei
~1.4-2.3 mya
A. robustus
Larger brain than gracile Australopithecines ~1.0-2.0 mya
Muscular Massive jaws, sagittal crest (pointy skull to support
massive jaw muscles), seed eaters
Did not lead to Homo line
Also called Paranthropus
Hominins as prey
Leopard canines fit punctures in Australopithecine skull
from Swartkrans, near Johannesburg, South Africa
Sexual dimorphism has been declining during the
course of Hominid evolution
Changes in sexual mating system???
in the process of polygamy  monogamy?
Homo habilis
“handy man”
~1.6-1.9 mya
Tool User
Figure 20.28 Oldowan
stone tools from Hadar,
These 2.3-million-yearold stone tools are among
the oldest known
Homo ergaster =
~1.5-1.8 mya
• First Migration Out of Africa
• First use of fire
Homo erectus sites
First Migration Out of Africa
Emergence of diverse
Homo species across a
broad geographic range
• Homo erectus spread out of Africa throughout Eurasia
and gave rise to multiple species of Homo in different
geographic regions
• Multiple sister taxa of Homo then evolved in different
geographic regions (H. sapiens, H. neaderthalensis,
Denisovans, sister Homo in Africa)
• The multiple sister species of Homo then came into
contact as the species migrated
• We descended from the more gracile line
(not sure which, exactly)
• And not necessarily the larger brained
Homo neanderthalensis
~28,000-300,000 yrs ago
Large Brains (larger than ours)
Occurred outside of Africa
Complex Culture
Reconstruction of Neanderthal
child from Gibraltar (Anthropological
Institute, University of Zurich)
Originally called Homo sapiens
neanderthalensis. Because of its larger
brain, we assumed that it had to be the
same species as us
Homo neanderthalensis
Did Homo sapiens (we) intermate with Neanderthals?
Why did they go extinct?
• Evolved outside of Africa (mostly
• Complex culture: more primitive tools
initially, but then after H. sapiens
invaded Europe out of Africa, they then
adopted H. sapiens tool technology
• Overlapped in geography with H.
sapiens in Europe for about 10,000
Reconstruction of Neanderthal
child from Gibraltar (Anthropological
Institute, University of Zurich)
• Extinct ~25,000 yrs ago
Geographic Range of H. neaderthalensis
Homo neanderthalensis
• Melanocortin 1 receptor (Mcr1) allele mutations
(loss of function) indicate that at least some had red
hair and fair skin (different mutation found in H.
sapiens)… likely to be independent evolution in low
UV environment
Reconstruction of Neanderthal
child from Gibraltar (Anthropological
Institute, University of Zurich)
• Large Brains (larger than us): same size
at birth as H. sapiens, but more rapid
growth during development, to achieve
ultimate larger size than H. sapiens (we
don’t know what this means in terms of
brain function)
Rib lesion is consistent with
injury by a long-range
projectile weapon traveling
along a ballistic trajectory
Generally, projectile
weapons are more
commonly associated
with H. sapiens.
Rib bones of a Neanderthal showing
puncture wounds consistent with weapons
of Homo sapiens
Homo neanderthalensis
• Buried dead, had rituals
• Art, radiocarbon dated to ~43,500
and 42,300 years ago in Spain, before
H. sapiens thought to have colonized
this region (older than H. sapiens art,
30,000 yr old Chauvet cave
Spain's Nerja caves
• Neanderthals probably had language (hyoid bone similar to
Homo sapiens, FOX2P gene shared with H. sapiens)
Figure 20.31 Hyoid bones from Homo
neanderthalensis (left) and a common
chimpanzee (right)
The hyoid is a small bone that connects the musculature of the tongue and
the larynx, and allows a wider range of tongue and laryngeal movements. The
bone found in Neanderthals is virtually identical to that of modern humans.
The presence of this bone implies that structured speech was anatomically
possible and that the repertory of sounds was wide enough to contain welldefined sets of phonemes, and not simply inarticulate guttural grunts.
New species of Homo
In March 2010, a finger bone fragment of a juvenile female that
lived about 41,000 years ago was found in Denisova Cave in Altai
Krai, Russia; a tooth and toe bone belonging to different members
of the same species have since been found.
This region was also inhabited at about the same time by
Neanderthals and perhaps modern humans.
Denisovans ranged from Siberia to Southeast Asia
Adaptive radiation of Hominin lineages
(Australopithecines and Homo) led to multiple
hominin species that overlapped temporally and
So, given this overlap in space and time, where did
modern Homo sapiens originate, and from which
And did other species of Homo contribute to the
genomic composition of Homo sapiens?
Human Evolution
(1) The Chimp-Human divide:
Hominins versus other Primates
(2) Adaptive Radiation of Hominin species
(3) The emergence of modern Homo
Where did Modern Humans
Come From?
(A) Multiregional Model
(B) “Out of Africa”
Two Models for Origins of Modern Humans
(A) Multiregional Model
(B) “Out of Africa”
Large Genetic Differences
among human populations
(1.5 Million Years)
Small Genetic Differences
among human populations
(small effective population size)
Genetic Diversity Equal
Most Diversity in Africa
(founder effect)
Modern Humans
Based on
mitochondrial data
alone it appeared that
the “Out of Africa”
hypothesis was correct,
with no introgression
with local species of
Vigilante et al.
1991 Science
Phylogeny of mitochondrial DNA
alleles are
in Africa
A phylogeny of modern H. sapiens using mitochondrial DNA
• Most of the Genetic Diversity is in Africa
• Ancestral alleles are in Africa
• Non-Africans are nested within the African clade (nonAfrican alleles are a subset of African alleles)
• Supports the scenario that H. sapiens originated in Africa,
and a small subset migrated out of Africa
Out of Africa
The last common ancestor of Homo sapiens
lived roughly 170,000 yrs ago (Ingman et al. 2000)
How are we related to our co-occurring sister
taxa? (which tended to split off earlier from our
ancestors, so they are often called “archaic”)
Neanderthals vs Modern Humans
Summary from several early studies based on DNA sequence data : Igman
et al. (2000), Krings et al. (2000), Ovchinnikov et al. (2000), Hoffreiter et al.
(2001), Green et al. (2006), Green et al. (2008)
According to this data set, Homo sapiens and Homo
neanderthalensis are quite distinct, separated by (~500,000 yrs);
that is, we split from a common ancestor ~500,000 years ago
Neanderthals form a separate Sister clade to Modern Humans; so,
they are a related sister species, NOT our direct ancestors
People call the other Homo species (Neanderthals, Denisovans,
African Homo erectus descendant) “archaic”, but they are out
sister taxa, NOT ancestral
• In the initial genetic studies (mtDNA and partial genome
sequencing), Neanderthal genes were absent in current human
• These preliminary results suggested there was no genetic
contribution from Neanderthals
• And suggested that they went extinct without leaving any genetic
signature in the current populations of Homo
However, more comprehensive genome
sequencing reveals genetic interbreeding between H.
sapiens and H. neanderthalensis (work from Svante Pääbo’s lab,
Science, 2010)
Overall, genome sequence is 99.5% to ~99.9% identical with
H. sapiens
The Neanderthal line began to diverge from Homo sapiens by
about 800,000 years ago and that we were "genetically
distinct" by 300,000 years ago
However, about 1-4% of DNA in Modern Europeans and
Asians was inherited from Neanderthals
No evidence of interbreeding between the two species in
Africa (Neanderthals did not occur in Africa, but originated in
Ozzy Osbourne's Genome Reveals Some Neandertal
By Katherine Harmon What genetic oddities does rock's Prince
of Darkness and beheader of bats have entangled deep in his
genetic code? Knome, the company that analyzed Ozzy's full
genome, divulges some of the details in a Q&A
Homo neanderthalensis
• Asymmetric Gene Flow: No evidence for
gene flow in the direction from modern
humans to Neanderthals. (only from
Neanderthals to Homo sapiens)
• This result would not be unexpected if contact
occurred between a small colonizing
population of H. sapiens and a much larger
resident population of Neanderthals.
• While modern humans share some nuclear DNA with the extinct
Neanderthals, the two species do not share any mitochondrial
DNA, which in primates is always maternally inherited.
• This observation has prompted the hypothesis that H. sapiens
females x male Neanderthals were able to generate fertile
offspring, whereas the progeny of female Neanderthals and male
H. sapiens were either rare, absent or sterile.
Introgression of Neanderthal genes
leading to local adaptation?
• The Neanderthal DNA in modern human populations includes some
of the genes for our HLA immune system (MHC loci).
• It has been suggested that this gave early modern human
immigrants to Europe and Asia critical protection to diseases that
had not existed in their African homeland.
• Mating with Neanderthals might have aided the migrating Homo
sapiens adapt to local pathogens.
• The initial genetic studies were not wrong, but simply told only
part of the story
• 1-4% introgression from Neandertals to H. sapiens represents
only a small part of the genome, and easy to miss in partial
genome sequence data.
Neanderthals vs Modern Humans
• So, the phylogeny above is correct across most of the genome
• Except, that the whole genome sequence data indicate some small
amount of introgression (1-4%) of DNA from Neanderthals to nonAfrican humans
Genome sequencing indicates that Denisovans are more
closely related to Neanderthals than to Homo sapiens
The estimated average time of divergence between
Denisovan and Neanderthal sequences is 640,000 years
ago, and that between both of these and the sequences of
modern Africans is 804,000 years ago.
About 1% of Chinese and up to 6% of the DNA of
Melanesians and Australian Aborigines are derived from
Callaway, 2011. Ancient DNA reveals secrets of human history, Nature
Hybridization with other Homo to acquire
immunity alleles
Half of the HLA (human leukocyte antigen, encode for MHC) alleles of
modern Eurasians represent archaic HLA haplotypes likewise inferred
to have introgressed from Denisovans or Neanderthals
For example, HLA type allele HLA-B*73 introgressed into humans in
west Asia from Denisovans
These alleles, of which several encode unique or strong ligands for
natural killer cell receptors, now represent more than half the HLA
alleles of modern Eurasians and also appear to have been later
introduced into Africans.
The apparent over-representation of these alleles suggests a positive
selective pressure for their retention in the human population.
Abi-Rached et al. 2011. The Shaping of Modern Human Immune
Systems by Multiregional Admixture with Archaic Humans. Science.
Introgression with other
Homo lineages in Africa?
Contemporary African
populations contain a small
proportion of genetic
material (~2%) that
introgressed ~35,000 years
ago from an “archaic” (sister)
species of Homo that split
from the ancestors of
anatomically modern
humans ~700,000 years ago
Studying the genomes of our sister species
relative to our genome reveals genes that are
uniquely Homo sapiens and that have
undergone selection during our recent history
(last few hundred thousand years)
Neanderthals abd Denisovans were successful
lineages of Homo for 300-400,000 years.
We have only been around for ~120,000
Will we survive as long as our sister taxa, or go
extinct sooner?
Multiple Migrations out of Africa: Migrations out of Africa by Homo
erectus (3), Neanderthals (2), Denosovans (blue), Homo sapiens (1)
Homo sapiens
Homo neanderthalensis
Homo erectus
Origins of Homo sapiens
(1) “Out of Africa” is mostly correct, as anatomically modern
Homo sapiens emerged out of Africa ~120,000 years ago
(2) Such that genetic divergences among modern human
populations are small
(2) Most of the Genetic Diversity is in Africa and a clade nested
within the African clade is found outside of Africa, indicating
that ancestral populations originated in Africa, followed by
recent founder effects and genetic drift as populations moved
out of Africa
Origins of Homo sapiens
(3) Mitochondrial and partial genome sequence data suggested that
all other Homo lineages went extinct without contributing to Homo
(4) HOWEVER, whole genome sequencing of other species of Homo
indicate that H. sapiens did mate with other species, at least with
Homo neanderthalensis and Denisovans and statistical genomic
analyses suggest intermating with African lineages of archaic Homo
(5) Thus, the “multiregional hypothesis” is partially correct, in that
modern populations of Homo did receive genetic contributions
from archaic Homo species (sister species) in different geographic
Origins of Homo sapiens
So, H. sapiens did emerge recently Out of Africa recently,
only ~100,000 years ago (most of the genome reflects
this genomic signature)
But then, intermated with local sister species of Homo in
different regions throughout Africa and Eurasia (1-4% of
the genome reflects this introgression)
Migrations of H. sapiens
Figure taken from: John K. Wiencke. 2004. Impact of race/ethnicity on
molecular pathways in human cancer. Nature Reviews Cancer 4:79-84
Native American
Frequency of allele
Pacific Islander
Genetic Drift
Loss of Alleles
Middle Eastern
NE African
Sub-Saharan African
Alleles at a locus
Tishkoff et al. 1996
Lots of reticulation among
“races” do not separate
out into neat groups
Evolution in Contemporary
Human Populations
Much of the genome in human populations is under
304 (9.0%) out of 3,377 potentially informative loci show
evidence of rapid amino acid evolution (Bustamante 2005)
Currently, signatures of negative selection (selection
against alleles) are used to find alleles that cause disease,
such as alleles that cause diabetes, obesity, etc.
Evolution in Contemporary
Human Populations
Modern lifestyle imposes selection (environment has
shifted recently)
Selection in response to diseases
 Microbial disease agents are evolving more quickly now
(antibiotics), and impose selection on human populations
For example, AIDS is the leading cause of deaths worldwide,
and is applying intense selection on human populations
Genocide and war
Example: more than 90% Native Americans killed off
 Many other examples of Genocide leading to decimation of
ethnic groups (loss of genetic diversity)
Recombination among previously isolated populations
New gene combinations (novel genotypes)
 Increases in heterozygosity
We are products of our Evolutionary History
Hunter-gather lifestyle: 95% of our evolutionary history
Diets (typically High fiber)
Exercise (walk 7-10 miles/day)
Lower calorie diet resulting in later menses,
fewer children (no more than 4, spacing of
children due to lactation)
Smaller Groups (~25)
Our environment has shifted
The Onion:
Human Feet Originally Used For Walking,
Anthropologists Report
July 22, 1998 | ISSUE 48•17 ISSUE 33•25
OXFORD, ENGLAND—A new report in the Journal Of The
Anthropological Society Of Oxford reveals that human feet
were likely once used as a means of extravehicular
locomotion. "Apparently, as recently as 20 years ago, the
foot was used in a process called 'walking,' by which the
human body actually propelled itself," the report read.
"Starting sometime in the late 1970s, these crude early feet
gradually evolved into their present function of operating the
gas and brake pedals on automobiles." The same team of
researchers discovered in 1994 that the human brain was
once used for various problem-solving applications before
evolving into an absorption/storage unit for lyrics to TV-show
Evolution in Future Human
The Future: Genetic Engineering
 We
are already genetically
screening embryos following
invitro fertilization (see film
Gattaca 1997)
We should start thinking about the ethics involved
in genetic engineering humans (we are already
engineering agricultural species)
(1) Genetic differences between human and chimps are small;
differences are mostly regulatory (development), especially
trans-regulatory… some cis-regulatory changes
(2) There was an adaptive radiation of hominid species ~3 mya,
such that several species coexisted
(3) Overall pattern toward larger brains, smaller teeth and jaws,
longer legs, less sexual dimorphism…
(4) Evolution is not perfect: jaw and tooth evolution was not that
well-coordinated (orthodontics); knee, ankle, hip problems
associated with bipedalism
(8) Evolution occurs in a jagged and bushy manner; i.e., we did
not always descend from the more robust or bigger brained
species, even though on average brain size was increasing
(6) Genetic data of human populations support that Modern
humans evolved in African relative recently, and then
migrated out of Africa ~100,000 years ago
(7) There is evidence of interbreeding between Homo sapiens
and our closest relatives Homo neanderthalensis, even
though the species are quite divergent and split ~500,000
years ago
(8) Genetic drift occurred as humans migrated out of Africa, with
loss of alleles from Africa, to Europe, to Asia, to Native North
(9) Large variance in male reproductive success in evident in
human populations (e.g. Genghis Khan)
(10) Human populations are under strong selection, especially in
response to diseases
1. Which of the following is TRUE regarding patterns of
human evolution?
(A) Homo neanderthalensis shares no alleles with Homo
sapiens (us), suggesting that interbreeding never occurred
(B) The lineage leading to Homo sapiens generally evolved
from the largest bodied and largest brained Hominid species
from any given time period
(C) Homo sapiens is the only Hominid species to leave Africa
(D) On average, brain size grew dramatically relative to body
size during the course of Hominid evolution
2. Based on what evidence do we now think that Homo sapiens
mated with other species of Homo, such as Denisovans and
(a) Sequences of mitochondrial genomes show that there has been
some introgression of genes from other species of Homo into
Homo sapiens
(b) Partial genome sequences from Homo neanderthalensis and
Denisovans (~15% of the genome sequence) began to show
evidence of introgression
(c) Full genome sequences from bone fragments of "archaic" Homo
species from Africa show evidence of introgression
(d) Alleles unique to Homo show evidence of introgression
(e) It was not until we obtained the whole genome sequences of our
sister species of Homo that we were able to determine that a
small proportion of human genomes (~1-5%) was derived from
other species of Homo
3. Current molecular genetic data in general support the hypotheses
that modern humans emerged out of Africa recently and then spread
all over the world (followed by some admixture with local Homo
species). Which line of evidence would support this hypothesis?
(A) Low genetic divergences among modern human populations, and
loss of alleles during migrations with greater distance from Africa
(B) Low genetic diversity among human populations, and increases in
genetic diversity with increasing distance from Africa
(C) Genetic Drift and genetic exchange with Homo neanderthalensis
(D) Large genetic divergences among modern populations, and loss
of alleles during migrations with greater distance from Africa
4. Which of the following statements is NOT supported by phylogenies of
modern humans?
(A) Movement of modern humans out of Africa was characterized by founder
effects with increasing distance from Africa.
(B) A very large proportion of the human genetic diversity exists among
(C) So far, there is no concrete evidence that Homo erectus or Homo
neanderthalensis contributed genetically to modern human populations.
(D) Ethnic groups of modern Homo sapiens do not separate out cleanly into
distinct clades, probably as a result of recent separation (incomplete lineage
sorting) and admixture
5. Which of the following would be a good strategy for
studying traits that are unique to Homo neanderthalensis?
(a) Examine genes that are divergent between Homo and other
(b) Examine genes that are shared between Homo sapiens,
Denisovans, and Neanderthals
(c) Examine genes that have introgressed into the Homo
sapiens genome from Homo neanderthalensis
(d) Examine genes that are present in the Homo
neanderthalensis genome, but not present in the Homo
sapiens genome
(e) Examine genes that are polymorphic in the Homo
neanderthalensis genome
6. Which types of alleles show an overrepresentation
of introgression from Neanderthals and Denisovans
into Homo sapiens populations?
(a) Paralogs
(b) hox genes
(c) MHC loci
(d) trans-acting factors
(e) Kernels of GRN
7. Which of the following is the MOST CORRECT regarding the origins of
modern Homo sapiens?
(a) Homo sapiens migrated out of Africa ~120,000 years ago,
and migrated across Europe and Asia without genetic
exchange with other species of Homo in Eurasia or Africa
(b) Lineages Homo each evolved independently in multiple
geographic regions for ~1 million years, leading to modern
Homo sapiens populations
(c) Homo sapiens migrated out of Africa ~120,000 years ago,
but there is now evidence that Homo neanderthalensis,
Denisovans, and other species of Homo contributed roughly
1-5% to the genomes of modern human populations
(d) Homo sapiens migrated out of Africa ~200,000 years ago
and intermated with Homo neanderthalensis, Denisovans,
while populations within Africa remained genetically the same
(e) The genus Homo experienced an adaptive radiation followed
by hybridization, leading to complete fusing of the species and
loss of genetic differentiation among species of Homo
Optional Slides
Evolution of HIV resistance in Human Populations
CCR5-Δ32 (or CCR5-D32 or CCR5 delta 32) is a mutant
allele of the receptor CCR5, where the deletion of a 32 base
pair segment makes the receptor nonfunctional
The allele has a negative effect upon T cell function, but
appears to protect against smallpox and HIV
 HIV has no receptor to bind to and cannot enter the cell
 This allele is found in 14% of Europeans
 HIV can impose selective pressure for CCR5-Δ32, increasing
the frequency of this allele in human populations (Sullivan et al.
Amy D. Sullivan et al. 2001. The coreceptor
mutation CCR5Δ32 influences the dynamics
of HIV epidemics and is selected for by HIV.
Proc Natl Acad Sci USA. 98: 10214–10219.
Evolution of HIV resistance in Human Populations
Some individuals have resistance against
HIV-1 due to high number of copies of the
CCL3L1 gene (Chemokine (C-C motif)
ligand 3-like 1).
This protein binds to chemokine receptor CCR5, and
competes with HIV for binding
Copy number of this gene varies among individuals; most
individuals have 1-6 copies in the diploid genome. With
increased copy number, there is more CCL3L1 expressed, and
so competition for the CCR5 binding site is increased. This
leads to a decrease in the ability of HIV to infect the cell.
Gonzales et al. 2005. The Influence of CCL3L1 Gene-Containing Segmental
Duplications on HIV-1/AIDS Susceptibility. Science. 307(5714):1434-1440.
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