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Transcript
Human
Evolution
"Light will be thrown on
the origin of man and his
history”
Charles Darwin, 1859
Human Evolution
OUTLINE:
(1) The Chimp-Human divide:
Hominins versus other Primates
(2) Adaptive Radiation of Hominin species
(3) The emergence of modern Homo
(NEXT TIME)
Human Evolution
OUTLINE:
(1) The Chimp-Human divide:
Hominins versus other Primates
(2) Adaptive Radiation of Hominin species
(3) The emergence of modern Homo
(NEXT TIME)
When did Humans
Evolve?
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
forest
Lead to Adaptive Radiations of early
humans?
How do we differ from
other Animals?
Animal
Phylogeny
First of all, we are
•Bilaterally Symmetric
•Triploblasts
•Coelomates
•Deuterostomes
•And Chordates
Phylogeny of mitochondrial cytochrome oxidase II alleles in humans
and the African Great Apes (Ruvolo et al. 1994)
Overall, genetic data
reveal that among
primates, we are
most closely related
to Chimpanzees.
Most molecular phylogenies place chimpanzees
as our closest relative. However, a minority of
molecular phylogenies do yield alternate
phylogenies (i.e. human-gorilla or gorilla-chimp
clades) due to incomplete lineage sorting. Review
in textbook by Herron (Chapter 20).
A rough cladogram based on dental
and skull characters
Cladogram of Hominan Species
(Based on morphology)
Not certain exactly which
Australopithecine led to Homo
Evolution of key anatomical features
Brain vs body size
Dramatic increase in brain
size (relative to body size)
during human evolution
Pilbeam and Gould, 1974
Consequences
of Bipedalism
• Pelvis tilt
• Stress on knees,
ankles, and back
• Non-grasping feet
• Freeing of hands
Evolution of Bipedalism

Sexual dimorphism has been declining during the
course of Hominid evolution

Changes in sexual mating system???

in the process of polygamy  monogamy?

Reduction in Jaw size

Reduction in tooth size

But insufficient
reduction in tooth size
or number to fit into
jaw!!! (how many of you
had braces?)

Evolution doesn’t
achieve perfection…
just enough to leave
enough offspring
Evolution of
Orthodontic
problems
Genetic differences between
humans and other primates
Humans: 23 pairs of chromosomes
Gorillas & Chimps: 24 pairs
Human chromosome 2 is derived from
the fusion of two chromosomes that
remain separate in the other great apes.
Hacia (2001)
H = Human
C = Chimp

As you can see from the previous
table, the genetic differences
between humans and our closest
living relatives (chimpanzee,
gorilla) are miniscule (tiny)
• Much of the genetic differences are due to differences in
gene regulation, specifically Evolution of Development
• As we learned in the last lecture, depending on where
the evolutionary changes are in the developmental
program, even a small number of developmental genetic
alterations could have profound changes on phenotype
Rapid evolution in the Homo lineage
Some examples of rapid evolutionary
genetic changes in Homo
Most of the functional evolutionary differences
between Humans and other great apes affect gene
regulation (which affects development)

Evolution of trans-acting elements
 Transcription factors (trans-regulatory changes)
 Epigenetic trans-regulators (such as microRNAs)
Genomic deletions (those that affect function
mostly affect gene regulation)

Rapid Evolution in Homo



Evolution of gene regulation  Evolution of
Development
Humans display a 3–5 times faster evolutionary
rate in divergence of developmental patterns,
compared to chimpanzees.
Particularly in brain tissue… affected in many
cases by trans-acting elements
Trans-regulatory evolution and the costs



As we know from previous lectures, it is thought that
regulatory evolutionary changes that are due to cisregulatory elements would occur more readily (than
trans), because of the increased pleiotropy of transacting elements
However, trans-regulatory changes can have profound
(large) impacts because of the many genes they regulate
Also, due to the pleiotropy, trans-regulatory changes
could have high costs (leading to tradeoffs)
Changes in developmental
genes and patterns of
gene expression are
greater in brain tissue than
other tissues in humans
relative to other primates
Most different in the Brain tissue
between Humans and other
primates (Enard et al. 2002)
Alleles unique to Homo



Enard et al. Nature 2002
FOXP2: gene implicated in
language (a transcription
factor)
2 amino acid substitutions in
Homo relative to chimps
Neanderthals share the
same derived allele
 Microcephalin (MCPH1): a gene that regulates brain size during
development and has experienced positive selection in Homo
 Thought a derived allele (Haplogroup D) introgressed into H. sapiens
by mating with extinct Homo species (Next Lecture,
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1635020/)


Most differences between Homo
and Chimps are due to
evolutionary changes in gene
expression, quantitative changes,
…rather than the presence of
unique alleles
PNAS 2009, 106: 22358-22363
http://www.pnas.org/content/106/52/22
358.abstract
Trans-regulatory evolution in the Humans
(focusing mainly on the brain)




Nowick et al (2009) identified 90 TF genes with significantly
different expression levels in human and chimpanzee brains,
among which the rapidly evolving KRAB-zinc finger genes are
markedly over-represented.
KRAB-zinc fingers have on average accumulated more amino
acid differences between humans and chimpanzees than other
genes, indicating that they may have contributed
disproportionately to the phenotypic differences between these
species
KRAB-ZNFs affect transcription; they are transcription factors
with an N-terminal KRAB domain and C-terminal zinc
fingers
The functions of many of these TFs are unknown
Differential gene expression between humans and chimps
• Most expression differences were seen in testis
• 25% of transcription factors examined (18 out of 79) in this
study showed changes in expression in the human brain
Nowick et al. 2009
Evolution of transcription factors in
the Human Brain (Nowick et al. 2009)



The TFs form 2 tight gene networks (Fig 3), coordinatelyregulated in expression in the brain (co-regulating 2 sets of
functional categories of genes, Fig. 5), indicating dramatic
shifts within larger biological pathways
The TFs are involved in regulation of energy metabolism,
vesicle transport, and related functions required to build and
maintain the larger and more complex human brain
Human TFs are more interconnected with each other than
those of chimpanzees
Network of transcription factor (TF) genes that show
evolutionary shifts in the human brain
Module 1:
Dominated by TF
genes up-regulated
in human brain
Module 2:
Dominated by
downregulated
TFs
Both modules are enriched for primate-specific KRAB-ZNF genes
Network of transcription factor (TF) genes that show
evolutionary shifts in the human brain
Module 1:
Dominated by TF
genes up-regulated
in human brain
Module 2:
Dominated by
downregulated
TFs
The coordinated regulation suggests that expression of these
transcription factors is regulated by a common regulatory element or
interacting elements (perhaps transcription factors)…
So, maybe: Master transcription factors  regulate transcription
factors downstream
Increases in
links of human
transcription
factors


So, what functions are these transcription
factors regulating?
What are the differences between humans and
chimps?
Functions of genes associated with transcription factors that
underwent evolution in the human brain (2 functional modules)


Module 1- Upregulated in
Humans relative to
chimpanzee: TF-associated
genes highly enriched for
functional categories involved in
transcription, ubiquitination,
and vesicular transport
Module 2- Downregulated in
Humans relative to
chimpanzee: TF-associated
genes, over-represented with
functional categories
corresponding to translation,
mitochondrial function and
energy metabolism
Functions of genes associated with transcription factors that
underwent evolution in the human brain (now shown in
comparison to the chimpanzee)
Evolution at the level of epigenetic trans-regulators
Evolution of transcription factors and epigenetic trans-regulators
(micro RNAs) in the brain
Human vs Chimp
divergence
Figure 3. Trans-effects on developmental pattern divergence in
the prefrontal cortex of the brain (Somel et al. 2011 Plos Biology)
Genomic deletions in the
Human relative to
chimpanzee
McClean et al. 2011 Nature
Specific Deletions in the Human genome
(McClean et al. 2011 Nature)
• 510 deletions in humans relative to chimpanzees
• The deletions are almost exclusively in non-coding regions
and affect gene regulation
• The deletions are enriched near genes involved in steroid
hormone signaling and neural function
• Deletions of tissue-specific enhancers may thus
accompany both losses and gains of traits in the human
lineage, and provide specific examples of the kinds of
regulatory alterations and inactivation events long proposed
to have an important role in human evolutionary
divergence.
Specific Deletions in the Human genome
(McClean et al. 2011 Nature)
Primate penile spines. Philip
Reno, Stanford University
• One deletion in Homo removes a sensory vibrissae and penile
spine enhancer from the human androgen receptor (AR) gene, a
molecular change correlated with the anatomical losses of
androgen-dependent sensory vibrissae (whiskers) and penile
spines (penis spines) in Homo (loss at ~700,000 yrs ago)
• Another deletion removes a forebrain subventricular zone
enhancer near the tumor suppressor gene: growth arrest and
DNA-damage inducible, gamma (GADD45G), a loss correlated with
expansion of specific brain regions in humans
Evolution of the Homo brain



The accelerated evolution of human brain expression
appears to mainly involve remodeling of
developmental patterns (evolution of development)
Much of the changes are due to trans-regulatory
evolution (transcription factors and micro RNAs)
Some changes due to gene deletions in the Homo
lineage (mostly regulatory regions, like the enhancers
mentioned)
Evolutionary Tradeoffs associated
with rapid brain evolution



Particularly since much of the evolution of the brain
appears to be due to trans-regulatory evolution,
…greater pleiotropic constraint of trans-acting
factors (leading to consequences for other
functions)
Gene deletions could also lead to costs
Evolutionary Tradeoff between Large
Brain and Cancer Susceptibility?



Loss of tumor suppressor gene in Homo 
promoting excessive brain growth
Humans appear to be less efficient than
chimpanzees in carrying out programmed cell
death
Might in part be why humans have a much
higher rate of cancer than chimpanzees
Gaurav Arora, Nalini Polavarapu, John F. McDonald. 2009.
Did natural selection for increased cognitive ability in humans
lead to an elevated risk of cancer? Medical Hypotheses
Rapid evolution of the
brain in Homo


Rapid evolution  new
opportunities, but also new
problems: Evolution of many
psychiatric disorders
Humans are unique among animals
in being susceptible to certain
neuropathologies
Neurodegeneration with Aging


Alzheimer's disease in the later stages of
life
Even healthy aging in humans is marked by
variable degrees of neural deterioration
and cognitive impairment, such as shrinking
of the brain not found in aging chimpanzees
Schizophrenia
Many genes that are expressed in
Schizophrenia are genes that experienced
rapid positive selection in Homo

Khaitovich et al. 2008. Metabolic changes in schizophrenia
and human brain evolution. Genome Biology.
http://genomebiology.com/2008/9/8/R124
Human Evolution
OUTLINE:
(1) The Chimp-Human divide:
Hominins versus other Primates
(2) Adaptive Radiation of Hominin species
(3) The emergence of modern Homo
(NEXT TIME)
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
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
Phylogeny of Hominan Species
(Based on morphology)
Not certain exactly which
Australopithecine 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
“Lucy”
Gracile
Australopithecines
~2.4-2.8 mya
A. africanus
~3.0-3.9 mya
A. afarensis
A. afarensis
Robust
Australopithecines
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
Homo habilis
“handy man”
~1.6-1.9 mya
Tool User
Figure 20.28 Oldowan
stone tools from Hadar,
Ethiopia
These 2.3-million-yearold stone tools are among
the oldest known
?
Homo ergaster = erectus
~1.5-1.8 mya
First Migration Out of Africa
First use of Fire (South African cave ~1 million yrs ago)
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, archaic 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
Europe)
• 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
years
Reconstruction of Neanderthal
child from Gibraltar (Anthropological
Institute, University of Zurich)
• Extinct ~25,000 yrs ago
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)
Homo neanderthalensis
• Large Brains (larger than us): same size
at birth as us, but more rapid growth
during development
• More brain function devoted to vision
and movement
(http://www.sciencedaily.com/releases/2013/0
3/130319093639.htm)
Reconstruction of Neanderthal
child from Gibraltar (Anthropological
Institute, University of Zurich)
Geographic Range of H. neaderthalensis
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
paintings)
Spain's Nerja caves
• Neanderthals probably had language (hyoid bone similar to
Homo sapiens, FOXP2 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.
Denisovans
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
Why did our congeners (all other
species of Homo) go extinct?



Hypotheses: climate change?
We killed them directly
We domesticated dogs 40,000 and as a
consequence became superior at hunting
Questions



Adaptive radiation of Hominin lineages
(Australopithecines and Homo) led to multiple
hominin species that overlapped temporally and
geographically
So, given this overlap in space and time, where did
modern Homo sapiens originate, and from which
species?
And did other species of Homo contribute to the
genomic composition of Homo sapiens?
Human Evolution
OUTLINE:
(1) The Chimp-Human divide:
Hominins versus other Primates
(2) Adaptive Radiation of Hominin species
(3) The emergence of modern Homo
(NEXT TIME)
Where did Modern Humans
Come From?
(A) Multiregional Model
(B) “Out of Africa”
Two Models for Origins of Modern Humans
Predictions
(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
Everywhere
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
Homo
Vigilante et al.
1991 Science
Phylogeny of mitochondrial DNA
Ancestral
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
populations
• 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)
http://www.sciencemag.org/content/328/5979/710.full




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
Europe)


Ozzy Osbourne's Genome Reveals Some Neandertal
Lineage
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
http://www.scientificamerican.com/a
rticle.cfm?id=ozzy-osbourne-genome
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
Denisovans



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
Denisovans
Callaway, 2011. Ancient DNA reveals secrets of human history, Nature
http://www.nature.com/news/2011/110809/full/476136a.html
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.
http://www.sciencemag.org/content/334/6052/89.full
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
Migrations and Distribution of Homo erectus (green), Neanderthals
(olive), Denosovans (blue), Homo sapiens (red)
Homo erectus in Europe
gave rise to
Neanderthals
Homo erectus in
Asia gave rise to
Denisovans
Homo sapiens
Homo neanderthalensis
Homo erectus
4 Denisovans
Genetic exchange between different
species of the genus Homo

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)
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
sapiens
(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
regions
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)
How long will we last?



Neanderthals abd Denisovans were successful
lineages of Homo for 300-400,000 years.
We have only been around for ~120,000
years…
Will we survive as long as our sister taxa, or go
extinct sooner?
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
Asian
European
Genetic Drift
during
Human
Migrations
Loss of Alleles
Middle Eastern
NE African
Sub-Saharan African
Alleles at a locus
Tishkoff et al. 1996
Lots of reticulation among
populations
“races” do not separate
out into neat groups
How will we evolve next?
Evolution in Contemporary
Human Populations



Much of the genome in human populations is under
selection
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
recently…
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
Populations

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)
Summary
(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
Summary
(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
America
(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 statement is FALSE regarding genetic differences
between humans and other apes?
(a) There are structural evolutionary differences in the
alleles of FOXP2 that are unique to Homo sapiens and
Homo neanderthalensis versus those of chimpanzees
(b) The genome sequences of humans and other great
apes are mostly identical, with less than 2% differences in
coding sequences
(c) Some key differences between human and chimpanzee
gene expression appear to be due to differences in
expression of transcription factors
(d) The transcription factors that differ in expression
between humans and chimpanzees form networks of
coordinately-regulated genes (all up or down in expression
as a unit)
(e) Most genetic differences between humans and chimps
appear to be due to cis-regulatory changes
2. Which of the following is FALSE regarding human brain
evolution?
(a) Rapid brain evolution in humans is likely due to
evolutionary changes in developmental genes
(b) Rapid brain evolution in humans might involve rapid
evolution of expression of trans-acting factors, such as
microRNAs
(c) Percentage of genes that are differentially expressed
between humans and chimpanzees are much greater in the
brain than in other tissues, such as the testis (male sex
organs)
(d) Rapid brain evolution in humans might involve rapid
evolution of expression of trans-acting factors, such as
transcription factors
(e) A gene deletion of a tumor suppressor gene that
allowed growth in the brain might also allow the
proliferation of cancer, leading to an evolutionary tradeoff
3. What are some anatomical features that do NOT
distinguish humans from other great apes?
(a) Bipedalism
(b) Low brain to body size ratio in Homo
(c) Shape of the pelvis
(d) Language
(e) Reduction in tooth and jaw size in Homo
4. Which of the following is FALSE regarding genetic differences
between humans and their closest relatives (chimpanzees)?
(A) Most of the DNA sequences are identical between humans
and chimps; only about 1.6% of total sequence, and only about
1% of the coding region differs
(B) Physical differences between humans and chimps are largely
caused by differences in regulatory genes, such as those involved
in gene expression (such as in the brain)
(C) Humans do not have unique genes relative to chimpanzees.
All the differences are due to the regulation (turning off and on) of
shared genes
(D) A few mutations in a few genes could affect biochemical or
cellular processes on a global scale (across all cells or causing
profound effects on biochemical pathways)
5. Which of the following is false regarding Hominin
evolution?
(a) All hominin fossil species prior to Homo erectus are
found only in Africa
(b) Evolution of Homo body parts was not synchronous,
such that the brain, organ tissues, jaw, teeth, etc.
diverged at different rates
(c) Australopithecines are less likely to have needed
braces to straighten their teeth relative to species of
Homo
(d) The lineage leading to Homo sapiens was generally
derived from the larger bodied and larger brained
ancestral species
(e) During the course of hominin (Australopithecines
and Homo) evolution several different hominin species
co-existed at the same time.
Answers:
1E
2C
3B
4C
5D
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
Neanderthals?
(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
Africans.
(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
primates
(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
Answers







1D
2E
3A
4C
5D
6C
7C
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.
2001)

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
CCL3L1
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.
Genetic Diagnostics

Genetic testing for Ancestry and disease alleles
has become very common

For example, “23andMe”:

https://www.23andme.com/