Lecture 24 : Human Origins and Signatures of
Selection
April 11, 2014
Announcements
 Switched labs 11 and 12
 Phylogenetics and Coalescence this week (lab 12 in
the manual)
 Signatures of selection next week (lab 11 in the
manual)
Last Time
Gene trees versus species trees
Coalescence
Influence of demographic factors on
coalescence times
Today
Human origins: Neanderthals and
Denisovans
Signatures of selection
Evidence for Ancient Population Structure in Nuclear
but not Mitochondrial Trees
Garrigan and Hammer 2006 Nature Reviews Genetics 7:669
Why does mitochondrion show
shorter coalescence times than
nuclear loci?
Why does rate vary much more
for nuclear loci?
Probability of Coalescence
 For any two lineages, function of
population size
Pcoalescence
1

2Ne
 Also a function of number of lineages
Pcoalescence
k (k  1) 1

2
2 Ne
where k is number of lineages
Models of Human Origin
Origin of
modern humans
Garrigan and Hammer 2006 Nature Reviews Genetics 7:669
Human Evolutionary History
http://www.cartage.org.lb/en/themes/sciences/paleontology/paleozoology/fossilhominids/ChartHumanEvolution/ChartHumanEvolution.htm
Neanderthals
 Occurred in Europe and central Asia from 400,000 to
30,000 ybp
 Morphological features distinguished them from
modern humans:
Nature 465:148, 2010
 strongly-built, stocky frame
 long, low skull with large cranial capacity
 Double-arched brow ridges
 occipital ‘bun’
 large nose, big front teeth
 Disappeared from fossil record shortly after Homo
sapiens appeared in Europe
http://www.msnbc.msn.com
What happened to the Neanderthals?
 Extinction with no genetic legacy?
 Do Neanderthals live on within our own genomes?
 Neanderthal genome sequences are now answering
those questions!
http://www.isayev.info
Archaic Genomics - Svante Pääbo
March 27, 2014, NIH
https://www.youtube.com/watch?v=M7VdRKQuAa8
Neanderthal Mitochondrial Sequence
 DNA extracted from bone fragments from 4 locations
 Sequenced using Next-Gen technology: Roche 454 FLX
 One individual (from Croatia) sequenced to great depth to
give reference genome
Briggs et al. 2009 Science 325:318
Neanderthal and Human Mitochondrial Tree
https://www.youtube.com/watch?v=M7VdRKQuAa8

Neanderthals and
humans show no
evidence of
admixture

Most ancient
Neanderthals
(easternmost) are
also most
differentiated

Very low population
structure and low
diversity in most
recent
Neanderthals

Low effective
population size?
Bottleneck? Stay
tuned.
Neanderthal “Complete” Genome Sequence
 DNA extracted from bone fragments from Vindijia Cave,
Croatia
 95-99% of DNA was from microbes
 Cut DNA with restriction enzymes with high CpG
recognition sites: eliminate bacterial DNA
 Sequenced with 454 and Illumina GAII
 5.3 Gb of sequence produced
Green et al. 2010 Science 328: 710
Distance from Modern Humans
Human-Neanderthal Hybridization
Distance from Neanderthal
 Segments in European human genome with high identity to Neanderthals are very different
from other human sequences
 Not true for African sequences
 Evidence for hybridization with Europeans, not Africans
Green et al. 2010 Science 328: 710
Human-Neanderthal Hybridization
 Four possible scenarios for
hybridization
 Scenario 3 most likely: hybridization
with ancestor of all modern Asian
and European lineages after splitting
from Africa
Green et al. 2010 Science 328: 710
Mithochondrial and Nuclear Stories are Different
https://www.youtube.com/watch?v=M7VdRKQuAa8
Why would mitochondrial DNA give a different
answer than nuclear DNA?
What other questions could be addressed with
ancient, introgressed DNA?
https://www.youtube.com/watch?v=M7VdRKQuAa8
https://www.youtube.com/watch?v=M7VdRKQuAa8
https://www.youtube.com/watch?v=M7VdRKQuAa8
https://www.youtube.com/watch?v=M7VdRKQuAa8
https://www.youtube.com/watch?v=M7VdRKQuAa8
https://www.youtube.com/watch?v=M7VdRKQuAa8
https://www.youtube.com/watch?v=M7VdRKQuAa8
https://www.youtube.com/watch?v=M7VdRKQuAa8
Expectations for Hybridization
Do Ancient Humans Show Larger Chromosome
Segments from Neanderthals than Modern
Humans?
45,000 year old human fossil genome
More admixture in 45,000 year old human (and Asians)
A new human ancestor: Denisovans
A new human ancestor: Denisovans
 Single finger bone and some
teeth discovered in cave in
Siberia
 Found in conjunction with
human-like artifacts: bracelets
and necklaces
 Sequenced mitochondrion and
whole genome (1.9X) using
Illumina GAII
 DNA sequence reveals this is not
a human bone!
http://www.time.com/time/health/article/0,8
599,1974903,00.html
Denisovans are closer to Neanderthals, but very different
Neanderthals
Modern Humans
Eurasians
Probably had
continued
introgression
from other
hominids after
divergence from
Africans
Patterns of Introgression in
Modern Humans and Relatives
Summary
• https://www.youtube.com/watch?feature=pla
yer_detailpage&v=M7VdRKQuAa8#t=1661
• \
Are Neanderthal and Denisovan
Genome Remnants Adaptive?
The main power of neutral theory is it
provides a theoretical expectation for
genetic variation in the absence of
selection.
Assume you take a sample of 100 alleles from a large
(but finite) population in mutation-drift equilibrium.
What is the expected distribution of allele frequencies in
your sample under neutrality and the Infinite Alleles
Model?
Number of Alleles
A.
B.
C.
10
8
6
4
2
2
4
6
8
10
2
4
6
8
10
Number of Observations of Allele
2
4
6
8
10