Bio380 Human Evolution: Waking the dead

Bio380: Waking the Dead Neanderthal 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
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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 200 th Birthday February 12 th 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
.

http://roughguidetoevolution.blogspot.com	1462
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Bio380 Human Evolution: Waking the dead

by Mark Pallen on Sep 30, 2011

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Bio380 Human Evolution: Waking the dead — Presentation Transcript