Iain MathiesonDepartment of Genetics
Perelman School of MedicineUniversity of Pennsylvania
Tracking the evolution of complex traits over space
and time with ancient DNA
Lascaux cave paintings, France ~15,000 BCE Image: Wikipedia user “Prof Saxx”
Images:
: Wikipedia(user Kurt Stueber)
: Czekaj-Zastawny 2008L. Wojcik
: Bartosiewicz et al 2006
Reconstruction of an LBK house ~5,400 BCE
Varna man, buried ~4,500 BCE with more gold than has been found in the entire rest of the world, up to that date.Image: Raiko Krauß
The Bronze Age brings dramatic changes in lifestyle and culture
What are the genetic changes associated with these shifts?
Olalde et al. 2018, Mathieson et al. 2018, Lipson et al. 2017 Fu et al. 2016, Mathieson et al. 2015, Allentoft et al. 2014, Haak et al. 2014, & many others
Steppe Ancestry < 4500 BPEarly Farmer 8500-4500 BPHunter-gatherer 14000-5000 BPUpper Paleolithic > 14000 BP
Bramanti et al. 2009, Skoglund et al. 2012, Lazaridis et al. 2014, Haak et al. 2015Allentoft et al. 2015, Mathieson et al. 2015, Lipson et al. 2017, Olalde et al. 2018
Early Farmers~8500 BP
Steppe Ancestry~4500 BP
Lazaridis et al. 2014, Haak et al. 2015
LCT
TLR1
SLC45A2
SLC22A4
MHC
ZSCAN31
DHCR7NADSYN1GRM5 ATXN2
OAS1
CHR13:31MbHERC2
CYP1A2
14 genome-wide significant signals of selection
Mathieson et al. 2015
LCT: Lactase persistence
NADSYN1/DHCR7: Vitamin D metabolism
FADS1/2: Decreased triglyceride levels
ATXN2/SHD2B3: Associated with celiac disease, Type 1 diabetes
SLC22A4: Ergothioneine uptake, celiac disease, IBD
CYP1A1: Metabolism of exogenous substances; caffeine.
SLC45A2, GRM5: Light skin pigmentation
HERC2/OCA2: Blue eye color
TLR1/6/10: Immunity, leprosy, TB and other mycobacterial resistance
OAS1/2/3: Viral resistance; Neanderthal introgressed haplotype
ZSCAN32: Autophagy
MHC: Immunity, everything.
Diet
Pigmentation
Immunity
Adaptation to agriculture
Figure: Gil McVean
West African
NorthernEuropean
Mathieson & Mathieson 2018
Lactase persistence postdates cattle domestication
LP allele appears~6500 years ago
LP allele starts to become common ~3000 years ago
Cattle domesticated> 10,000 years ago
First evidence of dairying ~8500 years ago
FADS1 variants post-date agriculture
Agriculture in Europe~8500 years ago
Derived allele not selected Until ~3000 years ago
Mathieson & Mathieson 2018
Mathieson & Mathieson 2018
SLC22A4 selection post-date agriculture
Agriculture in Europe~8500 years ago
Derived allele not selected Until ~4000 years ago
Mathieson & Mathieson 2018
Amylase copy number pre-dates agriculture
Evolution of pigmentation
Jablonski & Chaplin 2009
VLDLR-AS1
SMARCA2
MFSD12
SNX13
HERC2
SLC24A5DDB1
TMEM138
KITLG
TYROCA2
MC1R
IRF4
BNC2
ASIP
SLC45A2FLNB
SLC24A4
DUT
SLC12A1
MYEF2
ATP8B4
SHC4 CEP152
SST-RTP2
BEND7-PRPF18
54 pigmentation-associated variants
Dan Ju
Population* Based on 1KG
Score
African 0.61East Asian 0.59South Asian 0.50European 0.36
Score: proportion of pigmentation-increasing variants
Dan Ju
Variation in pigmentation in Europe 10,000 BP
Mathieson et al. 2018
HERC2 [OCA2] Eye color–associated rs12913832
Dan Ju
Evolution of stature
Differences in genetic height among ancient populations (N=1107)
∆SP = 0.4 s.d.P = 3 × 10-12
Hunter-gatherer
Early Farmer
Steppe Ancestry
025005000750010,00012,500
Date in years BP
Nor
mal
ized
poly
geni
c he
ight
scor
e
+2
-2
0
Steppe ancestry predicts present-day height
Skoglund & Mathieson 2018
R2 = 0.64
Collaborators & Funding
PennDan Ju
Other institutionsSara Mathieson (Swarthmore)Pontus Skoglund (Crick Institute)David Reich (Harvard)Christopher Ruff (Johns Hopkins)
Questions?
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