Human Migrations Saeed Hassanpour

Spring 2008

Introduction

• Population Genetics

Co-evolution of genes with language and cultural.

• Human evolution: genetics, history, statistics, physical/social anthropology, archaeology, demography, linguistic,...

Background

• Genetic variation discovery: ABO blood groups (1919).

Biochemical methods(e.g. PCR): stain, radioactive, fluorescent markers visualization.

• DNA sequencing and genotyping

Definition• Allele: Different forms of a gene.• Genotype: The specific allele in an

individual.• Phenotype: The expression of a

genotype.

Allele

Genotype

Phenotype

Homozygote

Homozygote

Heterozygote

Definition• Microsatellite: Short consecutive repeats:

• Single nucleotide polymorphism (SNP): Variation in a single nucleotide of a genome between two individuals.

AC ACAC ACACACACAC

Definition• Linkage disequilibrium (LD): Correlation

between alleles at two different position.

• Haplotype: Combination of alleles at multiple linked loci which are transmitted together.

Evolution• Evolutionary forces:

- Natural selection: Probability of survival and reproduction

Genetic drift: Change in allele frequencies entirely by chance.

Evolution

- Mutation: Change in nucleotide sequence of genes caused by copying error or exposure to radiation, chemical substance, viruses,...

Migration

Genetic Distance

Fixation Index (Fst): Measure of population differentiation.

• ΠBetween(ΠWithin): Average number of pairwise difference between two individuals sampled from different (the same) population.

ΠBetween

ΠWithin

Natural selection

• Find Genes which are candidates to have been under selection:

Very low and very high Fst distance.

Compare expected and observed values of Fst.

Evolutionary History

Fst matrix analysis:

- Phylogenetic tree

Based on SNP of 120 genes in

1,915 individuals

Evolutionary History

- Principle components

Based on 783

microsatellites in 1,027 individuals

Mitochondrial DNA• Mitochondrial DNA (mtDNA):

In mitochondria (out of nucleus)

• transmitted along only female lineages.

• No recombination.

High mutation rate:

• Abundance of polymorphic

Difficult genealogy reconstruction

NYR and Autosome

• None-recombining part of Y chromosome.

- Lower rate of the mutation

- Greater length of DNA

Autosome: non-sex chromosome.

TMRCA• Time of the fist major separation in

evolutionary tree between african and non-african.

Bayesian analysis and maximum-likelihood methods:

• Using mtDNA: TMRCA≈230,000

• Using NRY: TMRCA≈100,000

TMRCA

Polygyny vs. Polyandry

Fst Matrix Analysis

Oceania

America

E.Asia

C.S.Asia

Europe

Midl.East

Africa

Based on 650,000

SNPs in 938 individuals

Fst Matrix Analysis

• Fst vs. geographic distance

Based on SNP of 120 genes in

1,915 individuals

Fst Matrix Analysis

(A) Europe, (B) The Middle EastBased on 650,000

SNPs in 938 individuals

Genetic variance

• Partition molecular variance in Autosome, ChrX, Microsatellite:

Within population(WP)

• Among-population

-within-group(AP/WG)

• Among geographical region(AG)

Migration

Waypoints

Based on 783

microsatellites in 1,027 individuals

Heterozygosity

• α: population in Africa.

p~ui: probability of allele u in population i

Estimate of heterozygosity in population i:

Heterozygosity

• Expansion of modern human from a single center.

• Each migration is a sampling from the original population. (Serial Founder)

KNb

K K

1 2 n

Nb

Heterozygosity

• Considering only genetic drift

No migration between populations

• n bottleneck, Nb founders at each bottleneck

Reduction in heterozygosity by factor:

1-1/(2Nb)

Heterozygosity

Heterozygosity

Heterozygosity

Human Chimp

?

Drift vs. Selection

• Since regression explain 76%-78% of observed genetics variation

Lower bound on genetic drift effect: 76%-78%

• Upper bound on Selection effect: 22%-24%

Genes and Culture

Culture transmission: Vertically and Horizontally

Conclusion

• Out of Africa theory explain the Human genetic diversity:

Genetic distance

• Heterozygosity

Refrences

• The application of molecular genetic approaches to the study of human evolution, Cavalli-Sforza & Feldman, 2003

Support from the relationship of genetic and geographic distance in human populations for a serial founder effect originating in Africa, Ramachandran et al., 2005

• Worldwide Human Relationships Inferred from Genome from Genome-Wide Patterns of Variation, Jun Li et all., 2008