archaeology – “the scientific study of material remains (as fossil relics, artifacts, and...
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Archaeology – “the scientific study of material remains (as fossil relics, artifacts, and monuments) of past human life and activities”
Studies the time period starting at the Paleolithic time until the advent of literacy
Archaeology
Slide Credits to Vanessa Patel
From bones, compared genomes of three different Neanderthals with five genomes from modern humans from different areas of the world
The Neanderthal Genome
Figure 1- R. E. Green et al., Science 328, 710-722 (2010)
Slide Credits to Vanessa Patel
Fixation, Positive & Negative Selection
Neutral Drift Positive SelectionNegative Selection
How can we detect negative
selection?
How can we detect positive
selection?
How can we detect positive selection?
Ka/Ks ratio:Ratio of nonsynonymous tosynonymous substitutions
Very old, persistent, strong positive selection for a protein that keeps adapting
Examples: immune response, spermatogenesis
How can we detect positive selection?
Chr S1 S2 S3 S4 S5 S6
A 1 0 1 1 1 0
B 1 1 1 0 1 0
C 1 0 1 1 1 0
D 1 1 1 1 0 0
E 1 0 0 0 1 1
F 1 0 1 1 1 0
G 1 0 0 1 0 0
H 1 1 1 1 1 0
I 1 0 1 1 1 1
J 1 0 1 1 1 1
Core C
Extended Haplotype Homozygozity
Slide Credits:Marc Schaub
Chr S1 S2 S3 S4 S5 S6
A 1 0 1 1 1 0
B 1 1 1 0 1 0
C 1 0 1 1 1 0
D 1 1 1 1 0 0
E 1 0 0 0 1 1
F 1 0 1 1 1 0
G 1 0 0 1 0 0
H 1 1 1 1 1 0
I 1 0 1 1 1 1
J 1 0 1 1 1 1
Core C
• 3 core haplotypes: ch0 = 101 ch1 = 111 ch2 = 100
Extended Haplotype Homozygozity
Slide Credits:Marc Schaub
Chr S1 S2 S3 S4 S5 S6
A 1 0 1 1 1 0
B 1 1 1 0 1 0
C 1 0 1 1 1 0
D 1 1 1 1 0 0
E 1 0 0 0 1 1
F 1 0 1 1 1 0
G 1 0 0 1 0 0
H 1 1 1 1 1 0
I 1 0 1 1 1 1
J 1 0 1 1 1 1
Core C
• 3 core haplotypes: ch0 = 101 ch1 = 111 ch2 = 100
Extended Haplotype Homozygozity
Slide Credits:Marc Schaub
Chr S1 S2 S3 S4 S5 S6
A 1 0 1 1 1 0
B 1 1 1 0 1 0
C 1 0 1 1 1 0
D 1 1 1 1 0 0
E 1 0 0 0 1 1
F 1 0 1 1 1 0
G 1 0 0 1 0 0
H 1 1 1 1 1 0
I 1 0 1 1 1 1
J 1 0 1 1 1 1
Core C
• 3 core haplotypes: ch0 = 101 ch1 = 111 ch2 = 100
Extended Haplotype Homozygozity
Slide Credits:Marc Schaub
Chr S1 S2 S3 S4 S5 S6
A 1 0 1 1 1 0
B 1 1 1 0 1 0
C 1 0 1 1 1 0
D 1 1 1 1 0 0
E 1 0 0 0 1 1
F 1 0 1 1 1 0
G 1 0 0 1 0 0
H 1 1 1 1 1 0
I 1 0 1 1 1 1
J 1 0 1 1 1 1
Core C Given a core haplotype (101) and
a SNP (S6)
EHH is the conditional probability of two randomly chosen chromosomes to be homozygous from the core to S6 given that they include core haplotype 101
Extended Haplotype Homozygozity
Chr S1 S2 S3 S4 S5 S6
A 1 0 1 1 1 0
B 1 1 1 0 1 0
C 1 0 1 1 1 0
D 1 1 1 1 0 0
E 1 0 0 0 1 1
F 1 0 1 1 1 0
G 1 0 0 1 0 0
H 1 1 1 1 1 0
I 1 0 1 1 1 1
J 1 0 1 1 1 1
Core C EHH is the conditional probability of two randomly chosen chromosomes to be homozygous from the core to S6 given that they include core haplotype 101
Extended Haplotype Homozygozity
Slide Credits:Marc Schaub
EHH is the conditional probability of two randomly chosen chromosomes to be homozygous from the core to S6 given that they include core haplotype 101
Chr S1 S2 S3 S4 S5 S6
A 1 0 1 1 1 0
B 1 1 1 0 1 0
C 1 0 1 1 1 0
D 1 1 1 1 0 0
E 1 0 0 0 1 1
F 1 0 1 1 1 0
G 1 0 0 1 0 0
H 1 1 1 1 1 0
I 1 0 1 1 1 1
J 1 0 1 1 1 1
Core C
Extended Haplotype Homozygozity
Slide Credits:Marc Schaub
Chr S1 S2 S3 S4 S5 S6
A 1 0 1 1 1 0
B 1 1 1 0 1 0
C 1 0 1 1 1 0
D 1 1 1 1 0 0
E 1 0 0 0 1 1
F 1 0 1 1 1 0
G 1 0 0 1 0 0
H 1 1 1 1 1 0
I 1 0 1 1 1 1
J 1 0 1 1 1 1
Core C
Extended Haplotype Homozygozity
Slide Credits:Marc Schaub
Study of genes known to be implicated in the resistance to malaria.
Infectious disease caused by protozoan parasites of the genus Plasmodium
Frequent in tropical and subtropical regions
Transmitted by the Anopheles mosquito
Image source: wikipedia.org
Application: Malaria
Slide Credits:Marc Schaub
Image source: NIH - http://history.nih.gov/exhibits/bowman/images/malariacycleBig.jpg
Application: Malaria
Slide Credits:Marc Schaub
Image source: CDC - http://www.dpd.cdc.gov/dpdx/images/ParasiteImages/M-R/Malaria/malaria_risk_2003.gif
Application: Malaria
Slide Credits:Marc Schaub
Malaria and Sickle-cell Anemia
Allison (1954): Sickle-cell anemia is limited to the region in Africa in which malaria is endemic.
Image source: wikipedia.org
Distribution of malaria Distribution of sickle-cell anemiaSlide Credits:Marc Schaub
Malaria and Sickle-cell Anemia
Hypothesis: mutation causing sickle-cell anemia positively selected for the resistance to malaria.
Currat (2002) and Ohashi (2004) identify the mutations in the African respectively Asian populations.
Slide Credits:Marc Schaub
Malaria and Sickle-cell Anemia
Single point mutation in the coding region of the Hemoglobin-B gene (glu → val).
Heterozygote advantage: Resistance to malaria Slight anemia.
Image source: wikipedia.orgSlide Credits:Marc Schaub
Source: Ingram and Swallow. Population Genetics of Encyclopedia of Life Sciences. 2007.
Slide Credits:Marc Schaub
Lactose Intolerance
LCT, 5’
LCT, 3’
Source: Bersaglieri et al. Am. J. Hum. Genet. 2004.Slide Credits:Marc Schaub
Lactose Intolerance
Lactose Intolerance
Source: Catherine Janet Ellen Ingram and Dallas Mary Swallow. Population Genetics of Lactase Persistence and Lactose Intolerance advanced. Encyclopedia of Life Sciences. 2007.
Slide Credits:Marc Schaub
-13910*T associated with persistent lactose tolerance. Is this mutation causal?
Does not account for tolerance in sub-Saharan populations (Mulcare 2004).
Additional SNPs in an enhancer within 100bp are associated with lactose tolerance.
Several independent causes for lactose
tolerance (reviewed in Ingram 2009).Slide Credits:Marc Schaub
Finding the Causal Marker
Lactase persistence (litterature)Predicted lactase persistence
13910*T distribution
Source: Ingram et al. Lactose digestion and the evolutionary genetics of lactase persistence. Hum Genet. 2009 Jan;124(6):579-91.
Slide Credits:Marc Schaub