A Genomic Portrait of Haplotype Diversity and Signatures of Selection in Indigenous Southern African Populations

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Genome-wide analysis of human populations is useful in shedding light on the evolutionary history of the human genome, with a wide range of applications from reconstructing past associations between different population histories to disease mapping. In this manuscript we report on the application of genome-wide data to southern African populations and the identification of genome-wide signatures of selection pre- and post-admixture. Several signals of selection, before and after admixture, were identified, some of which involved loci associated with human diseases, including malaria, influenza, tuberculosis and HIV/AIDS. These results may reflect adaptations of southern African populations to infectious diseases. Consistent with previous studies, this study highlights the significance of the San in the genetics of human populations, as they are distinct from the other populations in many respects i.e. haplotype structure, locations of recombination hotspots, copy number and population structure. Furthermore, our study demonstrates the admixture of the San, Bantu-speaking populations and populations of Eurasian ancestry in some of the southern and eastern African populations. It illustrates the value in correcting for this stratification in future genome-wide association studies, and suggests that a future admixture mapping in these populations would likely be warranted and successful.

Vyšlo v časopise: A Genomic Portrait of Haplotype Diversity and Signatures of Selection in Indigenous Southern African Populations. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005052
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005052

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Zdroje

1. Frazer KA, Ballinger DG, Cox DR, Hinds DA, Stuve LL, et al. (2007) A second generation human haplotype map of over 3.1 million SNPs. Nature 449: 851–861. 17943122

2. Jakobsson M, Scholz SW, Scheet P, Gibbs JR, Vanliere JM, et al. (2008) Genotype, haplotype and copy-number variation in worldwide human populations. Nature 451: 998–1003. doi: 10.1038/nature06742 18288195

3. Li JZ, Absher DM, Tang H, Southwick AM, Casto AM, et al. (2008) Worldwide Human Relationships Inferred from Genome-Wide Patterns of Variation. Science 319: 1100–1104. doi: 10.1126/science.1153717 18292342

4. McVean G, Spencer CCA, Chaix R (2005) Perspectives on Human Genetic Variation from the HapMap Project. PLoS Genetics 1: e54. 16254603

5. The International HapMap C (2005) A haplotype map of the human genome. Nature 437: 1299–1320. 16255080

6. Cann HM, de Toma C, Cazes L, Legrand M-F, Morel V, et al. (2002) A Human Genome Diversity Cell Line Panel. Science 296: 261b–262.5. 11954565

7. Sabeti PC, Varilly P, Fry B, Lohmueller J, Hostetter E, et al. (2007) Genome-wide detection and characterization of positive selection in human populations. Nature 449: 913–918. 17943131

8. Tang K, Thornton KR, Stoneking M (2007) A new Approach for Using Genome Scans to Detect Recent Positive Selection in the Human Genome. PLoS Biology 5: e171. 17579516

9. McVean GAT, Myers SR, Hunt S, Deloukas P, Bentley DR, et al. (2004) The fine- scale structure of recombination rate variation in the human genome. Science 304: 581–584. 15105499

10. Voight BF, Kudaravalli S, Wen X, Pritchard JK (2006) A map of Recent Positive Selection in the Human Genome. PLoS Biology 4: e72. 16494531

11. Williamson S, Hubisz MJ, Clark AG, Payseur BA, Bustamante CD, et al. (2007) Localizing recent adaptive evolution in the human genome. PLoS Genetics 3: e90. 17542651

12. Stringer CB, Andrews P (1988) Genetic and fossil evidence for the origin of modern humans. Science 239: 1263–1268. 3125610

13. Conrad DF, Jakobsson M, Coop G, Wen X, Wall JD, et al. (2006) A worldwide survey of haplotype variation and linkage disequilibrium in the human genome. Nat Genet 38: 1251–1260. 17057719

14. Tishkoff SA, Williams SM (2002) Genetic analysis of African populations: human evolution and complex disease. Nat Rev Genet 3: 611–621. 12154384

15. Tishkoff SA, Kidd KK (2004) Implications of biogeography of human populations for 'race' and medicine. Nat Genet 36: S21–27. 15507999

16. Pickrell JK, Patterson N, Loh P-R, Lipson M, Berger B, et al. (2014). Ancient west Eurasian ancestry in southern and eastern Africa. Proc Natl Acad Sci:111(7):2632–7. doi: 10.1073/pnas.1313787111 24550290

17. Behar DM, Villems R, Soodyall H, Blue-Smith J, Pereira L, et al. (2008) The dawn of human matrilineal diversity. Am J Hum Genet 82: 1130–1140. doi: 10.1016/j.ajhg.2008.04.002 18439549

18. Campbell MC, Tishkoff SA (2008) African genetic diversity: implications for human demographic history, modern human origins, and complex disease mapping. Annu Rev Genomics Hum Genet 9: 403–433. doi: 10.1146/annurev.genom.9.081307.164258 18593304

19. Gonder MK, Mortensen HM, Reed FA, de Sousa A, Tishkoff SA (2007) Whole-mtDNA genome sequence analysis of ancient African lineages. Mol Biol Evol 24: 757–768. 17194802

20. Tishkoff SA, Gonder MK, Henn BM, Mortensen H, Knight A, et al. (2007) History of Click-Speaking Populations of Africa Inferred from mtDNA and Y Chromosome Genetic Variation. Mol Biol Evol 24: 2180–2195. 17656633

21. Knight A, Underhill PA, Mortensen HM, Zhivotovsky LA, Lin AA, et al. (2003) African Y chromosome and mtDNA divergence provides insight into the history of click languages. Curr Biol 13: 464–473. 12646128

22. Wood ET, Stover DA, Ehret C, Destro-Bisol G, Spedini G, et al. (2005) Contrasting patterns of Y chromosome and mtDNA variation in Africa: evidence for sex-biased demographic processes. Eur J Hum Genet 13: 867–876. 15856073

23. Watkins WS, Rogers AR, Ostler CT, Wooding S, Bamshad MJ, et al. (2003) Genetic variation among world populations: inferences from 100 Alu insertion polymorphisms. Genome Res 13: 1607–1618. 12805277

24. Ehret C (2001) An African classical age: Eastern and southern Africa in world history, 1000 B.C. to A.D. 400. Int. J. of Afric. Hist. Stud: 34, 667–669.

25. Ehret C, Posnansky M (1982).The archaeological and Linguistic Reconstruction of African History. California: University of California Press. 211–221p.

26. Henn BM, Gignoux CR, Jobin M, Granka JM, Macpherson JM, et al. (2011). Hunter-gatherer genomic diversity suggests a southern African origin for modern humans. PNAS 108:5154–5162. available:http://www.pnas.org/content/108/13/5154.full. Accessed February 3, 2011. doi: 10.1073/pnas.1017511108 21383195

27. Ehret C (1971) Southern Nilotic History: Linguistic Approaches to the Study of the Past. Chicago: Northwestern Univ. Press. 112–127 p.

28. Ehret C. (1974) Ethiopians and east Africans: The problem of Contacts. Nairobi: east African Publishing House Press.

29. Nurse GT, Weiner JS, Jenkins T (1985) The peoples of southern Africa and their affinities. New York: Oxford University Press. 209–256 p.

30. Soodyall H, Makkan H, Haycock P, Naidoo T (2008) The genetic prehistory of the Khoe and San. Southern African Humanities Khoekhoe and the earliest herders in southern Africa. pp. 37–48.

31. Jenkins T, Zoutendyk A, Steinberg A (1970) Gammaglobulin groups (Gm and Inv) of various southern African populations. Am. J. of Physical Anthropology 32: 197–218. 4191313

32. Besten MP (2006). Transformation and Reconstitution of Khoe-San Identities: AAS Le Fleur I, Griqua Identities and Post-apartheid Khoe-San Revivalism (1894–2004). Leiden: University of Leiden Press. 85–189 p

33. Lachance J, Vernotm B, Elbers CC, Ferwerda B, Froment A, et al. (2012) Evolutionary history and adaptation from high-coverage whole-genome sequences of diverse African hunter-gatherers. Cell:150: 457–469. Available: http://www.sciencedirect.com/science/article/pii/S0092867412008318. Accessed 3 August, 2012. doi: 10.1016/j.cell.2012.07.009 22840920

34. Elphick R (1985) Khoikhoi and the founding of white South Africa. Johannesburg: Ravan Press.

35. Gurdasani, D, Carstensen T, Tekola-Ayele F, Pagani L, Tachmazidou I, et al. (2014). The African Genome Variation Project shapes medical genetics in Africa. Nature. doi: 10.1038/nature13997

36. Schlebusch CM, Lombard M, Soodyall H. (2013). MtDNA control region variation affirms diversity and deep sub-structure in populations from southern Africa. BMC Evolutionary Biology. 13: 56. doi: 10.1186/1471-2148-13-56 23445172

37. Rosenberg NA, Pritchard JK, Weber JL, Cann HM, Kidd KK, et al. (2002) Genetic structure of human populations. Science 298: 2381–2385. 12493913

38. Tishkoff SA, Reed FA, Friedlaender FR, Ehret C, Ranciaro A, et al. (2009). The genetic structure and history of Africans and African Americans. Science 324:1035–1044 pp.

39. Pickrell JK, Patterson N, Barbieri C, Berthold F, Gerlach L, et al. (2012). The genetic prehistory of southern Africa. Nat. Communications 3:1143. Available:http://www.nature.com/ncomms/journal/v3/n10/full/ncomms2140.html. Accepted 17 September, 2012. doi: 10.1038/ncomms2140 23072811

40. Pickrell JK, Pritchard JK (2012) Inference of Population Splits and Mixtures from Genome-Wide Allele Frequency Data. PLoS Genet 8(11): e1002967. doi: 10.1371/journal.pgen.1002967 23166502

41. Hellenthal G, Busby J, Band G, Wilson J, Capelli C, et al. (2014) A Genetic Atlas of Human Admixture History. Science 343, 747 (2014); doi: 10.1126/science.1243518 24531965

42. Nielsen R, Signorovitch J (2003) Correcting for ascertainment biases when analyzing SNP data: applications to the estimation of linkage disequilibrium. Theoretical Population Biology 63: 245–255. 12689795

43. Tang H, Choudhry S, Mei R, Morgan M, Rodriguez-Cintron W, et al.(2007) Recent genetic selection in the ancestral admixture of Puerto Ricans. Am. J. Hum. Genet. 81: 626–633. 17701908

44. GeneCard database (HYPERLINK "www.genecards.org).

45. Chimusa ER, Daya M, Möller M, Ramesar R, Henn BM, et al. (2013) Determining Ancestry Proportions in Complex Admixture Scenarios in South Africa Using a Novel Proxy Ancestry Selection Method. PLoS ONE 8(9): e73971. doi: 10.1371/journal.pone.0073971 24066090

46. Baran Y, Pasaniuc B, Sankararaman S, Torgerson DG, Gignoux C, et al. (2012). Fast and accurate inference of local ancestry in Latino populations. Bioinformatics 28(10):1359–67. doi: 10.1093/bioinformatics/bts144 Available:http://bioinformatics.oxfordjournals.org/content/28/10/1359.full. Accessed 11 April, 2012. 22495753

47. Basu A, Tang H, Zhu X, Gu CC, Hanis C, et al. (2008) Genome- wide distribution of ancestry in Mexican Americans. Hum Genet 124(3):207–14. doi: 10.1007/s00439-008-0541-5 Available:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131689/. Accepted August 28, 2008. 18752003

48. Bryc K, Auton A, Nelson MR, Oksenberg JR, Hauser SL, et al. 2010. Genome-wide patterns of population structure and admixture in west Africans and African Americans. PNAS 107:786–791. Available:http://www.pnas.org/content/107/2/786.full. Accepted January 12, 2010. doi: 10.1073/pnas.0909559107 20080753

49. Oleksyk TK, Smith MW, O’Brien SJ. (2010) Genome-wide scans for footprints of natural selection. Philos Trans R Soc Lond B Biol Sci 365: 185–205. doi: 10.1098/rstb.2009.0219 20008396

50. Wenfei J, Shuhua X, Haifeng W, Yongguo Y, Yiping S, et al. (2012) Genome- wide detection of natural selection in African Americans pre- and post-admixture. Genome Res 22: 519–527. doi: 10.1101/gr.124784.111 22128132

51. Herman JP, Jullien N, Guillen S, Enjalbert A, Pellegrini I, et al. (2012) Research resource: A genome-wide study identifies potential new target genes for POU1F1. Mol. Endocrinol 26(8):1455–1463p. Available: http://dx.doi.org/10.1210/me.2011-130. Accessed 25 May 25 2012. doi: 10.1210/me.2012-1209 22844064

52. Inoue H, Mukai T, Sakamoto Y, Kimura C, Kangawa N, et al. (2012) Identification of a novel mutation in the exon 2 splice donor site of the POU1F1/PIT-1 gene in Japanese identical twins with mild combined pituitary hormone deficiency. Clin Endocrinol (Oxf) 76:78–87. doi: 10.1111/j.1365-2265.2011.04165 21722153

53. Rappaport N, Nativ N, Stelzer G, Twik M, Guan-Golan Y, et al. (2013) MalaCards: an integrated compendium for diseases and their annotation. Database (Oxford) 2013: bat018. Available: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3625956/. Accessed 12 April 12 2013.

54. Korn JM, Kuruvilla FG, McCarroll SA, Wysoker A, Nemesh J, et al. (2009). Integrated genotype calling and association analysis of SNPs, common copy number polymorphisms and rare CNVs. Nat. Genet. 40(10):1253–1260p. Available: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756534/. Accessed 4 October 2009.

55. McCarroll SA, Kuruvilla FG, Korn JM, Cawley S, Nemesh J, Wysoker A, et a. (2008) Integrated detection and population-genetic analysis of SNPs and copy number variation. Nat. Genet. 40: 1166–1174p.

56. Zhang J, Feuk L, Duggan GE, Khaja R, Scherer SW (2006) Development of bioinformatics resources for display and analysis of copy number and other structural variants in the human genome. Cytogenet Genome Res. 115: 205–214. 17124402

57. Redon R, Ishikawa S, Fitch KR, Feuk L, Perry GH, et al. (2006) Global variation in copy number in the human genome. Nat. 444: 444–454.

58. Conrad DF, Andrews TD, Carter NP, Hurles ME, Pritchard JK (2006) A high- resolution survey of deletion polymorphism in the human genome. Nat Genet 38: 75–81. 16327808

59. Sabeti PC, Schaffner SF, Fry B, Lohmueller J, Varilly P, et al. (2006) Positive natural selection in the human lineage. Science 312: 1614–1620. 16778047

60. Price AL, Helgason A, Palsson S, Stefansson H, St. Clair D, et al. (2009) The Impact of Divergence Time on the Nature of Population Structure: An Example from Iceland. PLoS Genet 5(6): e1000505. doi: 10.1371/journal.pgen.1000505 19503599

61. Bhatia G, Tandon A, Patterson N, Aldrich MC, Ambrosone CB, et al. (2014) Genome-wide scan of 29,141 African Americans finds no evidence of directional selection since admixture. Am. J. Hum Genet 95(4):437–44. Available: http://dx.doi.org/10.1016/j.ajhg.2014.08.011. doi: 10.1016/j.ajhg.2014.08.011 25242497

62. Seldin MF, Pasaniuc B, Price AL. (2011). New approaches to disease mapping in admixed populations. Nat. Rev. Genet. 12(8):523–8. doi: 10.1038/nrg3002 21709689

63. Bhatia G, Patterson N, Sankararaman S, Price A. L. (2013). Estimating and interpreting FST: The impact of rare variants. Genome research, 23(9), 1514–1521. doi: 10.1101/gr.154831.113 23861382

64. Adeyemo A, Rotimi C. (2014) What does genomic medicine mean for diverse populations? Mol Genet Genomic Med. 2(1): 3–6 doi: 10.1002/mgg3.63 24498625

65. University of Cape Town, Private Bag X3, Rondebosch 7701, South Africa.

66. University of Witwatersrand, 1 Jan Smuts Avenue Braamfontein 2000 Johannesburg, South Africa.

67. Glaubitz JC, Rhodes E, Dewoody A (2003) Prospects for inferring pairwise relationships with single nucleotide polymorphisms. Molecular Ecology 12: 1039–1047pp.

68. Patterson N, Price AL, Reich D (2006) Population structure and eigenanalysis. PLoS Genet. 2(12):e190. PMCID: PMC1713260. 17194218

69. Alexander DH, Novembre J., Lange K. Fast model-based estimation of ancestry in unrelated individuals. Genome Research, 19:1655–1664. doi: 10.1101/gr.094052.109 19648217

70. Scheet P, Stephens M (2006) A Fast and flexible statistical model for large-scale population genotype data: Applications to inferring missing genotypes and haplotypic phase. Am. J. Hum. Genet. 78: 629–644pp.