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 Heterozygote

Definition Microsatellite: Short consecutive repeats: Single nucleotide polymorphism (SNP): Variation in a single nucleotide of a genome between two individuals. AC

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 (F st ): Measure of population differentiation. Π Between (Π Within ): Average number of pairwise difference between two individuals sampled from different (the same) population. Π Between Π Within

Natural selection Find Genes which are candidates to have been under selection: Very low and very high F st distance. Compare expected and observed values of F st.

Evolutionary History F st matrix analysis:  Phylogenetic tree Based on SNP of 120 genes in 1,915 individuals

Evolutionary History  Principle components Based on 783 microsatellite s 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

F st Matrix Analysis Oceania America E.Asia C.S.Asia Europe Midl.East Africa Based on 650,000 SNPs in 938 individuals

F st Matrix Analysis F st vs. geographic distance Based on SNP of 120 genes in 1,915 individuals

F st Matrix Analysis (A) Europe, (B) The Middle East Based 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 microsatellite s 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)‏ K NbNb K K 12n NbNb

Heterozygosity Considering only genetic drift No migration between populations n bottleneck, N b founders at each bottleneck Reduction in heterozygosity by factor: 1-1/(2N b )

Heterozygosity

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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