Blood unites us: genetics and the population history of the British Isles

1. BAHSHE 07-07-2003 Blood unites us: genetics and the population history of the British Isles David T. Croke Royal College of Surgeons in Ireland dtcroke@rcsi.ie

3. History Anthropology Archaeology Human origins & population history Genetics Linguistics

4. What is the true history of the populations of these islands ? Successive waves of invasion versus Cultural exchange with little or no movement of people

5. Themes Genetic variation as a tool to ‘probe’ population history Anatomically Modern Humans - a brief history Palaeolithic & Neolithic Europe - the ‘Atlantic fringe’ More recent events in the population of these islands Population admixture in Ulster Genetics and ‘race’

6. Genetic variation as a tool to ‘probe’ human population history

7. ‘Keltic’ Aran Islands Waterford ‘Dinaric’ Harvard University Anthropological Survey of Ireland

8. Mourant, 1954

9. Genetic ‘markers’ used in population studies 1. ‘Classical’ protein markers 2. Y-chromosome - paternally inherited 3. Mitochondrial DNA - maternally inherited (mtDNA) 4. Recessive disease genes - biparentally inherited

10. The amount & rate of accumulation of variation can be used to infer genetic relationship / ancestry Surveys within species reveal enormous genetic variation between individuals On average, about 0.2% of our DNA differs between individual human beings Human and Chimpanzees differ by ≤ 2%

12. Tools • 1. Availability of the human genome sequence and of • genetic ‘markers’ • 2. Laboratory methods • - Polymerase Chain Reaction [PCR] • - DNA samples from modern populations • - ‘Ancient DNA (aDNA)’ • 3. Population genetics theory • 4. Mathematical & statistical tools

13. Anatomically Modern Humans - a brief history

14. Hominid Evolution Anatomically Modern Humans [AMH] emerged some 150 kYBP

15. Neanderthals and AMH did not interbreed Ancient & modern mtDNA; MDS analysis Krings et al., 1997 Caramelli et al., 2003

16. Neanderthals and AMH did not interbreed Ancient & modern mtDNA; MDS analysis Krings et al., 1997 Caramelli et al., 2003

17. Neanderthals and AMH did not interbreed Ancient & modern mtDNA; MDS analysis Krings et al., 1997 Caramelli et al., 2003

18. ‘Out of Africa’ - a global palaeolithic population expansion

20. The ‘Neolithic Transition’ (Agricultural revolution)

21. Genetic traces of the neolithic expansion Cavalli-Sforza et al., 1994

22. The ‘Atlantic fringe’ of Europe North-western Europe is different

23. Y-chromosome haplogroup 1.15 Hill et al., 2000

24. Y chromosome haplogroup diversity (a) Haplogroup 1.15 – the ‘Atlantic Modal Haplotype’ Wilson et al., 2001

25. Y chromosome haplogroup diversity (b) A Y haplogroup spectrum shared with the Basques - a palaeolithic ‘remnant’ Wilson et al., 2001

26. Y chromosome haplogroup diversity (c) Little similarity to the Near East  relatively little Neolithic influence on the ‘Atlantic’ populations Wilson et al., 2001

27. 6% 19% 67% 15% 21% 81% 23% 91% 41% 82% 14% 100% 10% 0% 63% 100% Neolithic contribution in Europe [Y data] Chikhi et al., 2002

28. mt DNA Y DNA Different male & female population histories [a] Y chromosome --> male-mediated gene-flow mt-DNA --> female-mediated gene-flow Wilson et al., 2001

29. mt DNA Y DNA Different male & female population histories [b] More female-mediated gene-flow (migration) between continental Europe and the Atlantic populations (excluding the Basques) Wilson et al., 2001

30. What about the Celts ?

31. 6,000 – 4,000 YBP Ireland & Britain were part of a Megalithic culture spread across Western Europe Palaeolithic & Neolithic admixture of peoples

32. The Celts were much later ! 1st millennium BC

33. Celticisation of these islands ? current model: diffusion of elements of celtic culture via trading links adoption of the celtic ‘cultural package’ by local ruling elites Cunliffe, 2001

34. Genetic evidence of more recent events in the population of these islands ?

39. Y chromosome census of the British Isles Samples: UK + Irl: 1,772 Norway: 201 Denmark }: 190 N. Germany} Capelli et al., 2003

40. Reference populations Capelli et al., 2003

41. Interpreting the data ? Capelli et al., 2003

42. Overall, a degree of similarity AMH+1 > 33% Capelli et al., 2003

43. Traces of Norwegian Viking admixture Capelli et al., 2003

44. N. German/Danish influences in England & Scotland Capelli et al., 2003

45. Recessive disease mutations Phenylketonuria (PKU) and the population history of Ulster

46. Unidentified Others R408W IVS12nt1 R243X F299C L348V I65T F39L Phenylketonuria [PKU] An inherited defect of amino-acid metabolism Due to mutations in the Phenylalanine Hydroxylase (PAH) gene [chromosome 12q] 29 different mutations have been identified in Ireland O’Neill et al., 1995 O’Donnell et al., 2002

47. Using PKU mutations to estimate Scottish admixture in Ulster

48. Ireland Scotland Ulster Analysis based on frequency data for 13 PKU mutations For Ulster as the hybrid population m = 0.46 Admixture proportion estimated as: m = (q2(rh-r2))/(q1r1-q2r2-rh(q1-q2)) O’Donnell et al., 2002

49. Does ‘race’ have a biological basis ?

50. H. sapiens (100%) Between regional populations (10%) Within regional populations (90%) Between local populations Within regions (5%) Between individuals within local populations (85%) Global human genetic diversity No biological basis for concepts of ‘race’ or ‘ethnicity’ After Relethford, 2003