genetics and human skeletal variation prof. tim weaver · prof. tim weaver the screen versions of...

Genetics and Human Skeletal VariationProf. Tim Weaver

1The screen versions of these slides have full details of copyright and acknowledgements

1

Genetics and Human Skeletal Variation

Prof. Tim Weaver

Department of Anthropology

University of California, Davis

Department of Human Evolution

Max Planck Institute for Evolutionary

Anthropology

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Why Are We Interested in Skeletal Variation?

Early attempts to classify humans into races

have often emphasized differences in skull form

These were often to support racist or eugenicist agendas

Today, the interest in skeleton variation is because the

skeleton is the part of the phenotype that remains from

extinct human ancestors

The physical record of human evolution consists

almost entirely of bones and teeth

3

Quantifying human skeletal variation

Genetic (and environmental) basis of human skeletal variation

Three observations about human genetic variation

How do patterns of human cranial variation compare

with patterns of human genetic variation?

Which evolutionary processes shaped patterns

of human cranial variation?

How do humans compare with other taxa?

Outline



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Traditional Caliper Measurements

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Landmarks and Virtual Objects

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Outline



7

Variation in Human Height

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Ronald Fisher

Infinitesimal Model

Fisher demonstrated that it was

possible to reconcile Mendelian

inheritance with the continuous

nature of most phenotypic variation

Only recently the data had become

available to evaluate how well the

infinitesimal model describes the

genetic basis of real phenotypes

9

0.00

0.25

0.50

– – – + + +

Single Locus Produces Discrete Phenotypes

+ -



10

0.00

0.09

0.19

0.28

0.38

– –– –

– –– +

– +– +

– ++ +

+ ++ +

Two Loci Produce More Phenotypes

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– –– –– –

+ ++ ++ +

– –– –– +

– –– +– +

– +– +– +

– +– ++ +

– ++ ++ +

0.00

0.08

0.16

0.23

0.31

Three Loci Produce Fairly Continuous Phenotypes

12Wood et al. Nat Genet. 2014

Multi-Locus Basis of Variation in Height

“The results are consistent with a genetic architecture

for human height that is characterized by a very large

but finite number (thousands) of causal variants”



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Classical Quantitative GeneticsModel of Heredity

Genetic basis of a metric trait is many genetic loci

that contribute equally and additively

(i.e., no interactions among them)

to the measurement value

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Phenotypic

Variance

Genetic

Variance

Environmental

Variance+ =

Genetic & Environmental Contribution to Phenotypic Variance

Between group variation can have a different cause

than within group variation

15Franz Boas



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Environment Can Influence Between-Group Variation in Head (Skull) Shape

Relethford JH. Am J Hum Biol. 2004

European-bornParents

US-bornOffspring

Cephalic Index

Bohemian

Hungarian

HebrewPolish

Italian

Scotch

Sicilian

86

84

82

80

78

Cephalic

Index (

%)

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Outline









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1) Among-region differences typically account

for a small percentage of the genetic variance

2) The genetic distance between groups increases

with the geographic distance between them

3) Within-group genetic variance decreases

with distance from sub-Saharan Africa

Three Observations about Human Genetic Variation



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Between-groupvariance

Total varianceWithin-group

variance

Partitioning Variance

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Genetic Differentiation of Major Geographic Regions

(e.g. Eastern Asia vs. Europe)

90% within regions(10% between regions)

Within region

Barbujani et al. 1997

Autosomal STRs


Within region

Autosomal SNPsFischer et al. 2006


Within regionThe Apportionment of

Human Diversity (1972)

R. C. Lewontin

21










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Relationship between Genetic Distance (Based on STRs) and Geographic Distance

Ramachandran et al. PNAS. 2005

0 5000 10000 15000 20000 25000

0.0

0

0.1

0

0.2

0

FS

T

Great circle geographic distance using waypoints (km)

23








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Great circle geographic distance using waypoints (km) from Addis Ababa, Ethiopia

Exp

ecte

d h

ete

rozyg

osi

ty

0 5000 10000 15000 20000 25000

0.5

0.4

0.3

0.2

0.1

0.0

Expected Heterozygosity and Geographic Distance

Ramachandran et al. PNAS. 2005



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Outline









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William W. Howells’Present-Day Cranial Sample

>2,500 individuals30 groups

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Genetics vs. Skull Form

86%within region

Relethford 1994

87%within region

Fischer et al. 2006

=



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Geographic distance (km)Geographic distance (km)

Sim

ilarity

Sim

ilarity

Genetics Cranial Form

Relationship with geographic distance

Relethford J H. Hum Biol. 2004

0 10,000 20,000 30,000

0.250

0.150

0.050

-0.050

0 10,000 20,000 30,000

0.050

0.025

0.000

-0.025

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>4,500 individuals105 groups

Tsunehiko Hanihara’sPresent-Day Cranial Sample

30Betti et al. Proc. R. Soc. B 2009

Decrease Within Group-Cranial Variance With Distance from Sub-Saharan Africa

Distance from sub-Saharan Africa (km)

Within

-gro

up v

ariance

(Male

s)W

ithin

-gro

up v

ariance

(Fem

ale

s)

0 5000 15,000 25,000 35,000

1.2

0.8

0.4

1.2

0.8

0.4



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The structure of human cranial variation is similar

to the structure of human genetic variation

However, the relationships between geography and

cranial variation are much weaker than those

between geography and genetic variation

Structure of Human Cranial Variation

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Outline









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Neutral Evolutionary Processes (Mutation and random genetic drift)

Neutral evolutionary processes are generally thought to play

an important role in shaping patterns of human genetic variation

It is often difficult to decide among neutral vs. adaptive

explanations for patterns of variation - hard to know exactly

how important neutral evolutionary processes were

in shaping human cranial form

Neutral evolutionary processes can’t ignored when trying

to understand patterns of cranial variation



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Between-group percentage of variance

0.00

Pro

bability

0.10 0.20 0.30 0.40

0.03

0.05

0.08

0.10

Nose Shape vs. Genetic Loci

Roseman and Weaver Am J Phys Anthropol. 2004

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Geographic Distribution of Nasal Index

Leong and Eccles Clin Otolaryngol. 2009

Nasal index 65- 66-70 71-75 76-80 81-85 86-90 91-100 +100

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Outline











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Pan troglodytes verus

Pan troglodytes troglodytes

Pan troglodytes schweinfurthii

Pan paniscus

West / Central Africa

3838

Region sub-S. Africa Europe E. Asia

sub-S. Africa 0.12 0.09

Europe 0.09

E. Asia



Europe 0.09

E. Asia

Present-day humans: craniometrics

Present-day humans: autosomal DNA (Fischer et al. 2006)

Weaver Am J Phys Anthropol 2014

FST Comparison for Humans

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Region Eastern Central Western Bonobo

Eastern 0.02 0.08 0.18

Central 0.06 0.18

Western 0.21

Bonobo


Eastern 0.09 0.32 0.54

Central 0.29 0.49

Western 0.68

Bonobo

Chimpanzees: craniometrics

Chimpanzees: autosomal DNA (Fischer et al. 2006)

FST Comparison for Chimpanzees




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Europe 0.52

E. Asia


Eastern 0.08 0.09 0.10

Central 0.07 0.12

Western 0.07

Bonobo

h2 Required for Match

Chimpanzees

Present-day humans


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Modern human(Cro-Magnon1)

Cranial Differences between Neanderthals and Humans

Neanderthal(La Chapelle-aux-Saints)

How does cranial divergence between Neanderthals

and modern humans compare with genetic divergence?

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Morphological Split Time Estimator

Weaver et al. PNAS 2008

Difference between

group means

Measures of the degree of departure from mutation-drift equilibrium

Additive genetic variance from

mutations



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Split Times

H. sapiens

H. neanderthalensis

P. paniscus (Bonobo)

P. troglodytes schweinfurthii(Eastern common chimpanzee)

P. troglodytes troglodytes(Central common chimpanzee)

P. troglodytes verus(Western common chimpanzee)

0.5

1.5

0.6

7.0

Split times in millions of years ago

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Neanderthal vs. modern human

P. t. verus vs. other P. t.

Split time

259,000 or 383,000depending on assumptions

27,000 or 151,000depending on assumptions

Morphological Split Time Estimates

Cranial differentiation constrained in chimpanzees

relative to modern humans and relative to Neanderthals

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Human cranial variation tends to be structured similarly

to human genetic variation in that:

Among-region differences typically account for a small

fraction of the morphological variance

The morphological distance between groups increases


Within-group morphological variance decreases


Neutral evolutionary process mediated by population history

appear to have played an important role in structuring

human cranial variation

Summary



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