 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  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 Figure 1- R. E. Green et al., Science 328, (2010)  Slide Credits to Vanessa Patel

Stoneking, Krause, Nature Reviews Genetics 2011

Signature Haplotypes:  Highly diverged  High LD over a long region

Neutral Drift Positive Selection Negative Selection How can we detect negative selection? How can we detect positive selection?

Ka/Ks ratio: Ratio of nonsynonymous to synonymous substitutions Very old, persistent, strong positive selection for a protein that keeps adapting Examples: immune response, spermatogenesis Ka/Ks ratio: Ratio of nonsynonymous to synonymous substitutions Very old, persistent, strong positive selection for a protein that keeps adapting Examples: immune response, spermatogenesis

X X X Slide Credits: Marc Schaub

ChrS1S1 S2S2 S3S3 S4S4 S5S5 S6S6 S1S1 S2S2 S3S3 S4S4 S5S5 S6S6 Slide Credits: Marc Schaub

ChrS1S1 S2S2 S3S3 S4S4 S5S5 S6S6 A B C D E F G H I J Core C Slide Credits: Marc Schaub

ChrS1S1 S2S2 S3S3 S4S4 S5S5 S6S6 A B C D E F G H I J Core C 3 core haplotypes: ch 0 = 101 ch 1 = 111 ch 2 = 100 Slide Credits: Marc Schaub

ChrS1S1 S2S2 S3S3 S4S4 S5S5 S6S6 A B C D E F G H I J Core C 3 core haplotypes: ch 0 = 101 ch 1 = 111 ch 2 = 100 Slide Credits: Marc Schaub

ChrS1S1 S2S2 S3S3 S4S4 S5S5 S6S6 A B C D E F G H I J Core C 3 core haplotypes: ch 0 = 101 ch 1 = 111 ch 2 = 100 Slide Credits: Marc Schaub

ChrS1S1 S2S2 S3S3 S4S4 S5S5 S6S6 A B C D E F G H I J Core C  Given a core haplotype (101) and a SNP (S 6 )  EHH is the conditional probability of two randomly chosen chromosomes to be homozygous from the core to S 6 given that they include core haplotype 101

ChrS1S1 S2S2 S3S3 S4S4 S5S5 S6S6 A B C D E F G H I J Core C  EHH is the conditional probability of two randomly chosen chromosomes to be homozygous from the core to S 6 given that they include core haplotype 101 Slide Credits: Marc Schaub

 EHH is the conditional probability of two randomly chosen chromosomes to be homozygous from the core to S 6 given that they include core haplotype 101 ChrS1S1 S2S2 S3S3 S4S4 S5S5 S6S6 A B C D E F G H I J Core C Slide Credits: Marc Schaub

ChrS1S1 S2S2 S3S3 S4S4 S5S5 S6S6 A B C D E F G H I J Core C 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 Slide Credits: Marc Schaub

Image source: NIH Slide Credits: Marc Schaub

Image source: CDC - R/Malaria/malaria_risk_2003.gif R/Malaria/malaria_risk_2003.gif Slide Credits: Marc Schaub

Source: Sabeti et al. Nature Slide Credits: Marc Schaub

Source: Sabeti et al. Nature Slide Credits: Marc Schaub

Source: Sabeti et al. Nature Slide Credits: Marc Schaub

Source: Sabeti et al. Nature Slide Credits: Marc Schaub

Source: Sabeti et al. Nature Slide Credits: Marc Schaub

 Allison (1954): Sickle-cell anemia is limited to the region in Africa in which malaria is endemic. Image source: wikipedia.org Distribution of malariaDistribution of sickle-cell anemia Slide Credits: Marc Schaub

 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

 Single point mutation in the coding region of the Hemoglobin-B gene (glu → val).  Heterozygote advantage:  Resistance to malaria  Slight anemia. Image source: wikipedia.org Slide Credits: Marc Schaub

Source: Ingram and Swallow. Population Genetics of Encyclopedia of Life Sciences Slide Credits: Marc Schaub

LCT, 5 ’ LCT, 3 ’ Source: Bersaglieri et al. Am. J. Hum. Genet Slide Credits: Marc Schaub

Source: Catherine Janet Ellen Ingram and Dallas Mary Swallow. Population Genetics of Lactase Persistence and Lactose Intolerance advanced. Encyclopedia of Life Sciences Slide Credits: Marc Schaub

 *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

Lactase persistence (litterature)Predicted lactase persistence 13910*T distribution Source: Ingram et al. Lactose digestion and the evolutionary genetics of lactase persistence. Hum Genet Jan;124(6): Slide Credits: Marc Schaub

Less time: Fewer mutations Fewer recombinations