Human Population Genetics

Human population migrations

• Out of Africa, Replacement– Single mother of all humans (Eve) ~150,000yr

– Single father of all humans (Adam) ~70,000yr

– Humans out of Africa ~40000 years ago replaced others (e.g., Neandertals)

– Evidence: mtDNA, Y chromosome

• Multiregional Evolution– Fossil records show a continuous change of

morphological features

– Proponents of the theory doubt mtDNA and other genetic evidence

Why humans are so similar

A small population that interbred reduced the genetic variation

Out of Africa ~ 40,000 years ago

Out of Africa

Migration of Humans

Migration of Humans

http://info.med.yale.edu/genetics/kkidd/point.html

Migration of Humans

Migration of Humans

http://info.med.yale.edu/genetics/kkidd/point.html

Human Variation in the Y Chromosome

Some Key Definitions

Mary: AGCCCGTACGJohn: AGCCCGTACGJosh: AGCCCGTACGKate: AGCCCGTACGPete: AGCCCGTACGAnne: AGCCCGTACGMimi: AGCCCGTACGMike: AGCCCTTACGOlga: AGCCCTTACGTony: AGCCCTTACG

Alleles: G, T

Major Allele: GMinor Allele: T

G/GG/GG/TG/GG/GG/GG/GT/TT/GT/G

Recombinations:At least 1/chromosomeOn average ~1/100 Mb

Linkage Disequilibrium:The degree of correlation between two SNP locations

Mom Dad

The Fall in Heterozygosity

The HapMap Project

The HapMap Project

The HapMap Project – Haplotype Blocks

The HapMap Project – LD

Fixation, Positive & Negative Selection

Neutral Drift Positive SelectionNegative Selection

How can we detect negative

selection?

How can we detect negative

selection?

How can we detect positive

selection?

How can we detect positive

selection?

Conservation and Human SNPs

CNSs have fewer SNPs

SNPs have shifted allele frequency spectra

Neutral CNS

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

How can we detect positive selection?

EHH test

Long Haplotypes –iHS test

Some highly selected loci

Example: Microencephalin gene