Human Polymorphisms and Genetic Anthropology

1. Human Polymorphisms and Genetic Anthropology Prof. Connie J. Mulligan Department of Anthropology September 20, 2012

2. Molecular genetics • Genetics is the study of heredity and variation of organisms • Classical, Mendelian genetics traces the inheritance of particular traits, or phenotypes • Molecular genetics is the study of heredity and variation using molecules, such as DNA • Traces the inheritance of genes or genetic variants Human karyotype

3. A little terminology • A gene is a piece of DNA that is responsible for the inheritance of a specific characteristic • eye color • ability to process lactate (drink milk) • Gene  protein Human chromosomes, Genetics, Hartl and Jones, 2000

4. A little terminology • A gene is a piece of DNA that is responsible for the inheritance of a specific characteristic • eye color • ability to process lactate (drink milk) • Gene  protein • Coding = genes (~3%) • Non-coding (~97%) Human chromosomes, Genetics, Hartl and Jones, 2000

5. DNA = Deoxyribonucleic acid • DNA is represented as a sequence of letters (nucleotide bases) • Adenosine = A • Guanine = G • Cytosine = C • Thymine = T • A-T and G-C pairs • DNA is a blueprint to direct the synthesis of proteins TGTG Genetics, 2001, Hartl and Jones, Jones and Bartlett Publishers, Inc

6. Genetic variants are changes in DNA sequence between individuals(A C-to-T variant is depicted in the DNA sequence below)

7. Terminology • Genetic variant • Genetic marker • Mutation • Polymorphism • SNP (single nucleotide polymorphism) • Biallelic marker • All of these terms are used to refer to genetic differences between individuals or populations

8. A little more terminology • Phenotype • Physical characteristics of an individual • Genotype • An individual’s DNA sequence or set of genetic markers • An individual’s genotype is responsible for an individual’s phenotype

9. How do you interpret a genetic variant? • What does a C-to-T change mean? • Smarter, prettier, faster, stronger??? • No, just different • Most variants are neutral = no effect • Genes make up only ~3% of genome and genes make our phenotype

10. Genetic anthropologyTypes of studies Peopling of the Americas Expansion out of Africa • Population history • Origins • Relationships • Populat’n movements • Migrations/colonization • Fission/fusion • Ancient DNA • Link ancestral and descendant pops • Disease • Origin of disease • Genetic basis of disease Domestication of the donkey Modified from Balaresque et al. 2007 Origin and expansion of Semitic speakers Genetic and cultural components to ethnicity and health

11. How do we interpret genetic variants to ask anthropological questions? • Look at the patterns of genetic variation • What has created the patterns of genetic variation? • Evolutionary history of humans Shriver and Kittles, 2004

12. ~ 200 kya Slides by Ryan Raaum

13. 100-200 kya

14. by 80 kya

15. ~ 60 kya

16. 45-60 kya

17. by 45 kya

18. 40-50 kya

19. ~ 35 kya Thanks, Ryan

20. Demographic history Neutral markers Not subject to natural selection Non-coding, ~97% Origin of anatomically modern humans Neanderthal genetics Adaptation Non-neutral markers Subject to natural selection Genes, ~3% genome Skin color, eye color, facial morphology, race Human evolution encompasses both demographic history and adaptation

21. Genetic evidence for the origin of modern humans H. sapiens are characterized by very little genetic variation relative to other primates What does this suggest? Jobling et al. 2003

22. Genetic evidence for the origin of modern humans H. sapiens are characterized by very little genetic variation relative to other primates What does this suggest? Relatively recent evolution Selection Or, more recent research suggests it might relate to generation time Longer generation time in humans → fewer opportunities for germ line mutations → slower mutation rate → less variation/shallower time depth Mutation rate follows generation time Humans < chimps hominoids < Old World monkeys Old World monkeys < marmosets

23. Genetic evidence for the origin of modern humans Greatest genetic diversity is in African populations Consistent w/ out-of-Africa theory of human origin Most genetic variation in humans is within populations, not between populations ~85% w/i pops ~5% b/t pops on same continent ~10% b/t pops on different continents, i.e. races

24. Nuclear DNA (nDNA = autosomes + sex chromosomes) homologous recombination single genome/diploid cell biparental inheritance variable mutation rate studied more recently multiple studied loci make comparisons more difficult Types of DNA • Mitochondrial (mtDNA) • no recombination • high copy number (but haploid) • maternal inheritance • high mutation rate • studied first • large comprehensive database Holland & Huffine 2001

25. Mitochondrial Eve- the mother of us all What is the mitochondrial Eve theory?

26. Mitochondrial Eve- the mother of us all What is the mitochondrial Eve theory? The idea that we all trace back to a single woman How can this be?

27. Mitochondrial Eve- the mother of us all What is the mitochondrial Eve theory? The idea that we all trace back to a single woman How can this be? B/c mitochondrial DNA does not recombine We have infinite nuclear ancestors b/c nuclear DNA does recombine

28. If we can all trace our maternal lineage back to a single women, then why don’t we all have the same mtDNA?

29. If we can all trace our maternal lineage back to a single women, then why don’t we all have the same mtDNA? MUTATION!

30. Race

31. Genetics and Race • What can biology/genetics tell us about race? • What can biology/genetics tell us about ourselves?

32. What can genetics tell us about race? • There is no genetic or biological definition for what we refer to as ‘race’ in humans • There is no Caucasian gene, no African gene, no Asian gene • Is there one gene that distinguishes one race from another? No.

33. Human evolution and genetic variation • Anatomically modern humans have been evolving for over 200,000 years and we are still evolving • There are no ‘pure’ human stocks and there never were • No populations are more highly evolved than others • Human populations are too closely related to be considered subspecies • There is a continuum of genetic variation across the globe

34. What genes do we have? • We have genes for: • ATP/energy production • DNA repair • Metabolic pathways • … • No one has ever identified a gene for: • Intelligence • Athleticism • Musical ability • Language ability • Work ethic • Personality

35. How do you interpret a genetic variant? • What does a C-to-T change mean? • Smarter, prettier, faster, stronger??? • No, just different • Most variants are neutral = no effect • Genes make up ~2% of genome

36. But there are different frequencies of alleles in different populations • Alleles differ in frequency between people and populations, genes don’t differ in frequency • Gene – DNA sequence that encodes a protein • Allele – one of several alternative forms of a DNA sequence (can be coding or non-coding) Human chromosomes, Genetics, Hartl and Jones, 2000 Types of alleles, Genetics, Hartl and Jones, 2000

37. But differences in allele frequencies doesn’t mean populations fall into racial categories • Most genetic variation among humans occurs within populations, not between them • Variation in gene frequency is distributed continuously, or clinally, in response to selection or genetic drift

38. Most genetic variation among humans occurs within populations, not between them

39. But differences in allele frequencies doesn’t mean populations fall into racial categories • Most genetic variation among humans occurs within populations, not between them • Variation in gene frequency is distributed continuously, or clinally

40. Variation in skin color in 22 populations

41. Bad sampling (A) can give the illusion of clusters, but good sampling (B) shows a cline in frequencies Serre, D., and S. Paabo. 2004. Genome Research 14:1679-1685.

42. But we look different! • We can see differences between people • e.g. dark-skinned, light hair, etc • But, only a few genes (out of ~20,000) determine skin color, hair color, etc. so it doesn’t take many variants to make us look different • The differences are literally only ‘skin deep’ • Skin color is controlled by levels of melanin • Three main genes for melanin production

43. What can genetics tell us about ourselves? • For a fee, lots of companies will tell you something about your ancestors based on a DNA sample • National Genographic, DNA Ancestry Project, DNA Tribes, Ancestral Origins • https://www.gtldna.net/ancestral-origins-dna-ancestry.html?src=google&gclid=CMaqk6jzv58CFQmdnAodOTr0zw

44. Neanderthal (+ other archaics) genetics

45. First publication of DNA sequences from a Neanderthal Sequence data from Neanderthal type specimen, found in Neander Valley, Germany in late 1800s Krings et al. 1997 – mtDNA HVRI sequence Krings et al. 1999 – mtDNA HVRII sequence Holland & Huffine 2001

46. Neanderthal genetics What is the evidence against interbreeding between Neanderthals and modern humans? Jobling et al. 2003

47. Neanderthal genetics Mitochondrial DNA data show that the majority of Neanderthal genetic variation lays outside modern human genetic variation Jobling et al. 2003

48. Neanderthal genetics Mitochondrial DNA data show that the majority of Neanderthal genetic variation lays outside modern human genetic variation Phylogenies show Neanderthal as an outgroup Jobling et al. 2003 Noonan 2010

49. Neanderthal genetics Mitochondrial DNA data show that the majority of Neanderthal genetic variation lays outside modern human genetic variation Phylogenies show Neanderthal as an outgroup MRCA b/t Neanderthal and humans is 4x older than MRCA of humans Jobling et al. 2003 Noonan 2010

50. Neanderthal genetics Means that Neanderthal mtDNA gene pool evolved for a long time, isolated from humans, and there is no support for a Neanderthal contribution to modern human mtDNA Jobling et al. 2003 Noonan 2010