3. 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

4. Why humans are so similar A small population that interbred reduced the genetic variation Out of Africa ~ 40,000 years ago Out of Africa

5. Migration of Humans

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

7. Migration of Humans

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

9. Human Variation in the Y Chromosome

10. Some Key Definitions Mary: AGCCCGTACG John: AGCCCGTACG Josh: AGCCCGTACG Kate: AGCCCGTACG Pete: AGCCCGTACG Anne: AGCCCGTACG Mimi: AGCCCGTACG Mike: AGCCCTTACG Olga: AGCCCTTACG Tony: AGCCCTTACG Mary: AGCCCGTACG John: AGCCCGTACG Josh: AGCCCGTACG Kate: AGCCCGTACG Pete: AGCCCGTACG Anne: AGCCCGTACG Mimi: AGCCCGTACG Mike: AGCCCTTACG Olga: AGCCCTTACG Tony: AGCCCTTACG Alleles: G, T Major Allele: G Minor Allele: T G/G G/T G/G T/T T/G G/G G/T G/G T/T T/G Recombinations: At least 1/chromosome On average ~1/100 Mb Linkage Disequilibrium: The degree of correlation between two SNP locations MomDad

11. The Fall in Heterozygosity

13. The HapMap Project

15. The HapMap Project – Haplotype Blocks

16. The HapMap Project – LD

17. Fixation, Positive & Negative Selection Neutral Drift Positive Selection Negative Selection How can we detect negative selection? How can we detect positive selection?

18. Conservation and Human SNPs CNSs have fewer SNPs SNPs have shifted allele frequency spectra CNSs have fewer SNPs SNPs have shifted allele frequency spectra Neutral CNS

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

20. How can we detect positive selection?

21. EHH test

22. Long Haplotypes –iHS test

23. Some highly selected loci

24. Example: Microencephalin gene