Bio380: Waking the DeadNeanderthal genes and genomes
Professor Mark Pallen
Bio380 Genes and Genomes lectures Lecture 1 Waking the Dead Lecture 2 Scatterlings of Africa Lecture 3 Major Population Movements: Peopling of
the World Lecture 4 The Wandering Gene Lecture 5 The Phylogenomics of Cancer Open Education
all lectures on YouTube and Slideshare Facebook Bio380 site Twitter feed #Bio380
Learning outcomes At the end of this lecture you should be able
to answer these questions: who were the Neanderthals? what is their relationship to us?
On this issue, you will be able to evaluate evidence from genes evidence from genomes
You will be able to describe the contribution of other archaic hominins to the modern human gene pool
Neandert(h)al
Valley near Düsseldorf Named after 17th
century pastor, Joachim Neumann
Thal became Tal in 1901 But old form still
used in taxonomy And annoyingly
both forms common in papers!
Discovery Numerous caves and rock shelters along valley,
including Kleine Feldhof Grotte In 1850s, limestone quarrying began by firm of
Beckershoff and Pieper; caves and valley walls removed
August 1856, skull cap and 15 postcranial bones recovered from Kleine Feldhof Grotte• first thought to be cave bear• shown to local teacher and natural historian
Fuhlrott, who identified them as human• first reported scientifically by Fuhlrott and
Schaaffhausen in 1857 Neanderthal 1 became type specimen for Homo
neanderthalensis “prequals”; Gibraltar 1848, Engis, Belgium,
1829
Discovery
Neanderthal 1 became type specimen for Homo neanderthalensis
“prequals” Gibraltar 1848 Engis, Belgium, 1829
Darwin Sept 1864 letter to his close friend, botanist Joseph Hooker: “F[alconer] brought me the wonderful Gibraltar skull.”
Re-discovery...
>400 specimens found
Timeline First proto-Neanderthal features ~350Kya Full-blown Neanderthals:
130Kya-30Kya died out by 50Kya in Asia ?survived to 24Kya in Europe
Overlapped in time and range with AMH but no overlap at any one site
Culture Mousterian culture
tool use, fire, burials, skinning cared for their injuried
? Language: hyoid bone found in 1983 Carnivores (evidence from isotopic studies)
cannibals? ritual defleshing
Anatomically distinct from AMH
differences > than in 2 chimp species more robust than AMH pronounced brow ridge projecting mid-face low flat elongated skull; occipital bun chinless with larger brains!?
Fate of the Neanderthals Coexistence for 15-20 ky Possible fates
Rapid extinction (genocide) Gradual extinction
unable to adapt to end of glaciation
cannot compete with humans, e.g. in hunting, running
Assimilation
Was their genetic exchange between AMH and Neanderthals?
OR
Africa Eurasia Africa Eurasia
Neanderthals
Neanderthals
What can sequences tell us Population genetics of modern populations
Are there sequences in Europeans not found elsewhere old enough to be Neanderthal in origin?
Torroni et al 1994 and Richards et al 1996 say no Ancient DNA
What do Neanderthal sequences look like? Relies on amplification or retrieval of sequences
from fossils Problem of contamination with human DNA
Mitochondrial DNA favoured because
100-10,000 copies per cell D-loop non-coding Maternal transmission
Neanderthal sequence outside modern human
range
Summary of Evidence from mtDNA Neanderthal mtDNA is quite different from
• all present human mtDNA sequences• ancient mtDNA sequences from AMHs
Common interpretations• two separate species• little or no admixture• consistent with out-of-Africa hypothesis
November 2006…
The verdict...
“By contrast, the complete Neandertal mtDNA now offers 133 such positions. This enables a reliable estimation of mtDNA
contamination by analyzing sequence reads from 454 libraries, rather than by PCR-based assays of the DNA
extracts. For example, when we do this in a small preliminary data set initially published from this fossil (Green et al., 2006), 10 of 10 sequences are classified as Neandertal.
However, in further unpublished sequencing runs from that library, 8 out of 75 diagnostic sequences derive from extant
human mtDNA, suggesting a contamination rate of 11% (CI = 4.7%–20%). This is in agreement with the suggestion (Wall
and Kim, 2007) that contamination occurred in that experiment.”
Darwin’s 200th BirthdayFebruary 12th 2009
1X draft sequence of Neanderthal genome announced ~60% of genome Sequenced 68.9 billion bases, 96% of which were
microbial in origin, to cull 3 billion bases of 1X Neanderthal genome
Three bone fragments from two Neanderthal women: no Y chromosome sequences
1000-2000 amino acid differences from AMH (cf 50,000 in chimp) No evidence of admixture No evidence of recently emerging non-African
Microcephalin or MAPT variants Divergence date ~800Ka Formal publication awaited!
Neanderthal genome Comparisons with chimp and AMH genomes
found 78 base substitutions that change protein sequences in AMH lineage; 5 proteins with >1 amino-acid change SPAG17 (axoneme protein); PCD16 (fibroblast
cadherin); TTF1 (transcription termination factor); CAN15 (unknown); RPTN (reptin, skin ECM protein)
Copy number changes, e.g. PRR20 68 copies in Neanderthal; 18 in AMH
Selective sweeps
Selective sweeps Neanderthals fall within variation in modern
humans in many parts of genome Allows search for regions subject to selective
sweeps in AMH Gene affected include:
THADA (associated with type II diabetes) genes implicated in cognitive ability
AUTS2, DYRK1A, NRG3, CADPS2
RUNX2, associated with cleidocranial dysplasia might explain skeletal differences in skull and upper
body between AMH and Neanderthals
But are Neanderthals more closely related to some AMHs than to others? Compare sites with derived SNPs in
Neanderthals/AMH Initial comparison to 2 European Americans, 2
East Asians and 4 West Africans shows Neanderthals significantly closer to non-Africans
Confirmed by comparisons with San, Yoruba, Han, French, Papuan, which also showed direction of flow is from Neanderthal to non-African humans
Chromosomal segments identified in which Craig Venter is more Neanderthal than African!
~1-4% of non-African genome is Neanderthal
Neanderthals
AMH
European
Chinese
Papuan
West African
San
Can molecules tell us anything about what Neanderthals were really like?
Specific studies on candidate genes and molecules
Neanderthals
AMH
European
Chinese
Papuan
West African
San
Denisovans
Overlap of archaic & AMH in Africa?
Conclusions Now have multiple Neanderthal mtDNA
sequences• All outside the range of human variation
Neanderthal genome sequence supports the idea of small-scale mixing
Now have evidence that (some) Neanderthals had pale skin, human-like FOXP2, bitter taste heterozygosity, blood group O
Other archaic admixture from Denisovans and unknown African population
More gene and genome sequences promised!
The last word?Are we really that surprised....?!
Recommended viewing
Search YouTube: For a bad (and I mean bad!) 1970s Neanderthal pop
song use search terms “Neanderthal” and “Hotlegs” For the amusing comparison of Neanderthals and
AMHs, use search terms “Eddie Izzard” and “Neanderthal”
Links to Chris Stringer’s talk and papers and other material available via WebCT
Image sources and rights http://www.flickr.com/photos/erix/142070879/sizes/z/in/photostream/ Some rights reserved by erix!
http://www.flickr.com/photos/54144832@N06/5530175310/lightbox/ Some rights reserved By Jorge Lucero
http://commons.wikimedia.org/wiki/File:Neanderthal_child_(1).jpg CC BY-SA 2.0 Ryan Somma
Stanislav Kozlovskiy http://commons.wikimedia.org/wiki/File:Skull_of_Teshik-Tash_Boy.jpg GNU Free Documentation License, V 1.2
http://en.wikipedia.org/wiki/File:Homo_sapiens_neanderthalensis.jpg Luna04 GNU Free Documentation License, Version 1.
http://en.wikipedia.org/wiki/File:Spy_Skull.jpg GNU Free Documentation License, Version 1.2 We El
http://commons.wikimedia.org/wiki/File:Neandertal_1856.jpg
http://www.flickr.com/photos/gianfrancogoria/3766258280/in/photostream/
http://en.wikipedia.org/wiki/File:Neanderthaler_Fund.png
http://www.flickr.com/photos/lwr/4019436274/sizes/m/in/photostream/
http://commons.wikimedia.org/wiki/File:Neanderthal_child.jpg
Jason Potter http://commons.wikimedia.org/wiki/File:Neanderthal_cranial_anatomy.jpg CC-BY-SA-2.5
http://www.flickr.com/photos/momentsnotice/5361847966/sizes/l/in/photostream/ CC BY-NC-SA 2.0 Massmatt
http://commons.wikimedia.org/wiki/File:MitoChondria_147.jpg
http://commons.wikimedia.org/wiki/File:Mitochondrial_DNA_en.svg
http://commons.wikimedia.org/wiki/File:Plos_paabo.jpghttp://en.wikipedia.org/wiki/File:Neandertaler-im-Museum.jpg
Chris Stringer kindly provided last two slides
.