Transcript Homo - Carol Lee Lab

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

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)
Geographic Range of H. neaderthalensis
Homo neanderthalensis
• Large Brains (larger than us): same size
at birth as us, but more rapid growth
during development (we don’t know
what this means in terms of brain
function)
• 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)
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
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?
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
(5) 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
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