Tracing genetic history of modern humans using X-chromosome lineages

Abstract

Genetic variability of the compound interrupted microsatellite DXS1238, in intron 44 of the dystrophin gene, provides evidence for a complex structure of the ancestral population that led to the emergence of modern humans. We sequenced DXS1238 in 600 X-chromosomes from all over the world. Forty four percent of African-specific chromosomes belong to the ancestral lineage that did not participate in the out-of-Africa expansion and subsequent colonization of other continents. Based on the coalescence analysis these lineages separated from those that contributed to the out-of-Africa expansion 366 ± 136 thousands years ago (Kya). Independently, the analysis of the variance in the repeat length and of the decay of the ancestral alleles of the two DXS1238 repeats, GT and GA, dates this separation at more than 200 Kya. This suggests a complex demographic history and genetic structure of the African melting pot that led to the emergence of modern humans and their out-of-Africa migration. The subsequent subdivisions of human populations among different continents appear to be preceded by even more structured population history within Africa itself, which resulted from a restricted gene flow between lineages allowing for genetic differences to accumulate. If the transition to modern humans occurred during that time, it necessarily follows that genes associated with this transformation spread between subpopulations via gene flow. Otherwise, in spite of subsequent anatomical variation, Homo sapiens as a species could have emerged in Africa already between 300 and 200 Kya, i.e. before the mitochondrial DNA and well before the Y-chromosome most recent common ancestors.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3

References

  1. Barreiro LB, Patin E, Neyrolles O, Cann HM, Gicquel B, Quintana-Murci L (2005) The heritage of pathogen pressures and ancient demography in the human innate-immunity CD209/CD209L region. Am J Hum Genet 77:869–886

    PubMed  Article  CAS  Google Scholar 

  2. Bauer G, Collard M, Stringer C (2004) On the reliability of recent tests of the Out of Africa hypothesis for modern human origins. Anat Rec A Discov Mol Cell Evol Biol 279:701–707

    Article  Google Scholar 

  3. Cavalli-Sforza LL, Feldman MW (2003) The application of molecular genetic approaches to the study of human evolution. Nat Genet 33(suppl):266–275

    PubMed  Article  CAS  Google Scholar 

  4. Chakraborty R (1990) Mitochondrial DNA polymorphism reveals hidden heterogeneity within some Asian populations. Am J Hum Genet 47:87–94

    PubMed  CAS  Google Scholar 

  5. Chen YS, Torroni A, Excoffier L, Santachiara-Benerecetti AS, Wallace DC (1995) Analysis of mtDNA variation in African populations reveals the most ancient of all human continent-specific haplogroups. Am J Hum Genet 57:133–149

    PubMed  CAS  Google Scholar 

  6. Clemens PR, Fenwick RG, Chamberlain JS, Gibbs RA, de Andrade M, Chakraborty R, Caskey CT (1991) Carrier detection and prenatal diagnosis in Duchenne and Becker muscular dystrophy families, using dinucleotide repeat polymorphisms. Am J Hum Genet 49:951–960

    PubMed  CAS  Google Scholar 

  7. Di Rienzo A, Donnelly P, Toomajian C, Sisk B, Hill A, Petzl-Erler ML, Haines GK, Barch DH (1998) Heterogeneity of microsatellite mutations within and between loci, and implications for human demographic histories. Genetics 148:1269–1284

    PubMed  CAS  Google Scholar 

  8. Dieringer D, Schlötterer C (2003) Microsatellite analyser (MSA): a platform independent analysis tool for large microsatellite data sets. Mol Ecol Notes 3:167–169

    Article  CAS  Google Scholar 

  9. Enard W, Przeworski M, Fisher SE, Lai CS, Wiebe V, Kitano T, Monaco AP, Paabo S (2002) Molecular evolution of FOXP2, a gene involved in speech and language. Nature 418:869–872

    PubMed  Article  CAS  Google Scholar 

  10. Estoup A, Jarne P, Cornuet JM (2002) Homoplasy and mutation model at microsatellite loci and their consequences for population genetics analysis. Mol Ecol 11:1591–1604

    PubMed  Article  CAS  Google Scholar 

  11. Falush D, Wirth T, Linz B, Pritchard JK, Stephens M, Kidd M, Blaser MJ, Graham DY, Vacher S, Perez-Perez GI, Yamaoka Y, Megraud F, Otto K, Reichard U, Katzowitsch E, Wang X, Achtman M, Suerbaum S (2003) Traces of human migrations in Helicobacter pylori populations. Science 299:1582–1585

    PubMed  Article  CAS  Google Scholar 

  12. Fan JB, Gehl D, Hsie L, Shen N, Lindblad-Toh K, Laviolette JP, Robinson E, Lipshutz R, Wang D, Hudson TJ, Labuda D (2002) Assessing DNA sequence variations in human ESTs in a phylogenetic context using high-density oligonucleotide arrays. Genomics 80:351–360

    PubMed  Article  CAS  Google Scholar 

  13. Fenner JN (2005) Cross-cultural estimation of the human generation interval for use in genetics-based population divergence studies. Am J Phys Anthropol 128:415–423

    PubMed  Article  Google Scholar 

  14. Forster P (2004) Ice Ages and the mitochondrial DNA chronology of human dispersals: a review. Philos Trans R Soc Lond B Biol Sci 359:255–264 (discussion 264)

    PubMed  Article  Google Scholar 

  15. Fu YX (1997) Statistical tests of neutrality of mutations against population growth, hitchhiking and background selection. Genetics 147:915–925

    PubMed  CAS  Google Scholar 

  16. Garrigan D, Hammer MF (2006) Reconstructing human origins in the genomic era. Nat Rev Genet 7:669–680

    PubMed  Article  CAS  Google Scholar 

  17. Griffiths RC, Tavare S (1994) Sampling theory for neutral alleles in a varying environment. Philos Trans R Soc Lond B Biol Sci 344:403–410

    PubMed  Article  CAS  Google Scholar 

  18. Griffiths RC, Tavaré S (1999) The age of a mutation in a general coalescent tree. Stochastic Models 14:273–295

    Article  Google Scholar 

  19. Harding RM, McVean G (2004) A structured ancestral population for the evolution of modern humans. Curr Opin Genet Dev 14:667–674

    PubMed  Article  CAS  Google Scholar 

  20. Harding RM, Fullerton SM, Griffiths RC, Bond J, Cox MJ, Schneider JA, Moulin DS, Clegg JB (1997) Archaic African and Asian lineages in the genetic ancestry of modern humans. Am J Hum Genet 60:772–789

    PubMed  CAS  Google Scholar 

  21. Harris EE, Hey J (1999) X chromosome evidence for ancient human histories. Proc Natl Acad Sci USA 96:3320–3324

    PubMed  Article  CAS  Google Scholar 

  22. Jaruzelska J, Zietkiewicz E, Batzer M, Cole DE, Moisan JP, Scozzari R, Tavare S, Labuda D (1999) Spatial and temporal distribution of the neutral polymorphisms in the last ZFX intron: analysis of the haplotype structure and genealogy. Genetics 152:1091–1101

    PubMed  CAS  Google Scholar 

  23. Kaessmann H, Heissig F, von Haeseler A, Paabo S (1999) DNA sequence variation in a non-coding region of low recombination on the human X chromosome. Nat Genet 22:78–81

    PubMed  Article  CAS  Google Scholar 

  24. Kimura M, Ohta T (1973) The age of a neutral mutant persisting in a finite population. Genetics 75:199–212

    PubMed  CAS  Google Scholar 

  25. Kivisild T, Metspalu M, Bandelt HJ, Richards M, Villems R (2006) The world mtDNA phylogeny. In: Bandelt HJ, Macaulay V, Richards M (eds) Human mitochondrial DNA and the evolution of Homo sapiens. Springer, Berlin, pp 149–173

    Google Scholar 

  26. Labuda D, Zietkiewicz E, Yotova V (2000) Archaic lineages in the history of modern humans. Genetics 156:799–808

    PubMed  CAS  Google Scholar 

  27. Lahr MM, Foley RA (1998) Towards a theory of modern human origins: geography, demography, and diversity in recent human evolution. Am J Phys Anthropol Suppl 27:137–176

    Article  Google Scholar 

  28. Lovell A, Moreau C, Yotova V, Xiao F, Bourgeois S, Gehl D, Bertranpetit J, Schurr E, Labuda D (2005) Ethiopia: between Sub-Saharan Africa and western Eurasia. Ann Hum Genet 69:275–287

    PubMed  Article  CAS  Google Scholar 

  29. Macaulay V, Hill C, Achilli A, Rengo C, Clarke D, Meehan W, Blackburn J, Semino O, Scozzari R, Cruciani F, Taha A, Shaari NK, Raja JM, Ismail P, Zainuddin Z, Goodwin W, Bulbeck D, Bandelt HJ, Oppenheimer S, Torroni A, Richards M (2005) Single, rapid coastal settlement of Asia revealed by analysis of complete mitochondrial genomes. Science 308:1034–1036

    PubMed  Article  CAS  Google Scholar 

  30. McDougall I, Brown FH, Fleagle JG (2005) Stratigraphic placement and age of modern humans from Kibish, Ethiopia. Nature 433:733–736

    PubMed  Article  CAS  Google Scholar 

  31. Mellars P (2006) Going east: new genetic and archaeological perspectives on the modern human colonization of Eurasia. Science 313:796–800

    PubMed  Article  CAS  Google Scholar 

  32. Nachman MW, Crowell SL (2000) Estimate of the mutation rate per nucleotide in humans. Genetics 155:1855–1864

    PubMed  CAS  Google Scholar 

  33. Plagnol V, Wall JD (2006) Possible ancestral structure in human populations. PLoS Genet 2:e105

    PubMed  Article  Google Scholar 

  34. Quintana-Murci L, Semino O, Bandelt HJ, Passarino G, McElreavey K, Santachiara-Benerecetti AS (1999) Genetic evidence of an early exit of Homo sapiens sapiens from Africa through eastern Africa. Nat Genet 23:437–441

    PubMed  Article  CAS  Google Scholar 

  35. Richards M, Bandelt HJ, Kivisild T, Oppenheimer S (2006) A model for the dispersal of modern humans out of Africa. In: Bandelt HJ, Macaulay V, Richards M (eds) Human mitochondrial DNA and the evolution of Homo sapiens. Springer, Berlin, pp 225–265

    Google Scholar 

  36. Rosenberg NA, Pritchard JK, Weber JL, Cann HM, Kidd KK, Zhivotovsky LA, Feldman MW (2002) Genetic structure of human populations. Science 298:2381–2385

    PubMed  Article  CAS  Google Scholar 

  37. Schaffner SF (2004) The X chromosome in population genetics. Nat Rev Genet 5:43–51

    PubMed  Article  CAS  Google Scholar 

  38. Schaffner SF, Foo C, Gabriel S, Reich D, Daly MJ, Altshuler D (2005) Calibrating a coalescent simulation of human genome sequence variation. Genome Res 15:1576–1583

    PubMed  Article  CAS  Google Scholar 

  39. Schneider S, Roessli D, Excoffier L (2000) Arlequin: A software for population genetics data analysis. 2.000 edn. Genetics and Biometry Laboratory, Department of Anthropology, University of Geneva, Switzerland

    Google Scholar 

  40. Shimada MK, Panchapakesan K, Tishkoff SA, Nato AQ Jr, Hey J (2007) Divergent haplotypes and human history as revealed in a worldwide survey of x-linked DNA sequence variation. Mol Biol Evol 24:687–698

    PubMed  Article  CAS  Google Scholar 

  41. Slatkin M (1994) An exact test for neutrality based on the Ewens sampling distribution. Genet Res 64:71–74

    PubMed  CAS  Article  Google Scholar 

  42. Stringer C (2002) Modern human origins: progress and prospects. Philos Trans R Soc Lond B Biol Sci 357:563–579

    PubMed  Article  Google Scholar 

  43. Tajima F (1989) Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123:585–595

    PubMed  CAS  Google Scholar 

  44. Tang H, Siegmund DO, Shen P, Oefner PJ, Feldman MW (2002) Frequentist estimation of coalescence times from nucleotide sequence data using a tree-based partition. Genetics 161:447–459

    PubMed  CAS  Google Scholar 

  45. Tattersall I, Schwartz J (2000) Extinct humans. Westview Press, New York

    Google Scholar 

  46. Tishkoff SA, Dietzsch E, Speed W, Pakstis AJ, Kidd JR, Cheung K, Bonne-Tamir B, Santachiara-Benerecetti AS, Moral P, Krings M (1996) Global patterns of linkage disequilibrium at the CD4 locus and modern human origins [see comments]. Science 271:1380–1387

    PubMed  Article  CAS  Google Scholar 

  47. Underhill PA, Shen P, Lin AA, Jin L, Passarino G, Yang WH, Kauffman E, Bonne-Tamir B, Bertranpetit J, Francalacci P, Ibrahim M, Jenkins T, Kidd JR, Mehdi SQ, Seielstad MT, Wells RS, Piazza A, Davis RW, Feldman MW, Cavalli-Sforza LL, Oefner PJ (2000) Y chromosome sequence variation and the history of human populations. Nat Genet 26:358–361

    PubMed  Article  CAS  Google Scholar 

  48. Underhill PA, Passarino G, Lin AA, Shen P, Mirazon Lahr M, Foley RA, Oefner PJ, Cavalli-Sforza LL (2001) The phylogeography of Y chromosome binary haplotypes and the origins of modern human populations. Ann Hum Genet 65:43–62

    PubMed  Article  CAS  Google Scholar 

  49. Wakeley J (2003) Inferences about the structure and history of populations: coalescents and intraspecific phylogeography. In: Singh RS, Uyenoyama MK (eds) The evolution of population biology. Cambridge University Press, Cambridge, pp 193–215

    Google Scholar 

  50. Watson E, Forster P, Richards M, Bandelt HJ (1997) Mitochondrial footprints of human expansions in Africa. Am J Hum Genet 61:691–704

    PubMed  CAS  Google Scholar 

  51. Watterson GA (1978) The homozygosity test of neutrality. Genetics 88:405–417

    PubMed  Google Scholar 

  52. White T, Asfaw B, DeGusta D, Gilbert H, Richards G, Suwa GH, Owell C (2003) Pleistocene Homo sapiens from Middle Awash, Ethiopia. Nature 423:742–747

    PubMed  Article  CAS  Google Scholar 

  53. Xiao FX, Yotova V, Zietkiewicz E, Lovell A, Gehl D, Bourgeois S, Moreau C, Spanaki C, Plaitakis A, Moisan JP, Labuda D (2004) Human X-chromosomal lineages in Europe reveal Middle Eastern and Asiatic contacts. Eur J Hum Genet 12:301–311

    PubMed  Article  CAS  Google Scholar 

  54. Zietkiewicz E, Yotova V, Jarnik M, Korab-Laskowska M, Kidd KK, Modiano D, Scozzari R, Stoneking M, Tishkoff S, Batzer M, Labuda D (1997) Nuclear DNA diversity in worldwide distributed human populations. Gene 205:161–171

    PubMed  Article  CAS  Google Scholar 

  55. Zietkiewicz E, Yotova V, Jarnik M, Korab-Laskowska M, Kidd KK, Modiano D, Scozzari R, Stoneking M, Tishkoff S, Batzer M, Labuda D (1998) Genetic structure of the ancestral population of modern humans. J Mol Evol 47:146–155

    PubMed  Article  CAS  Google Scholar 

  56. Zietkiewicz E, Yotova V, Gehl D, Wambach T, Arrieta I, Batzer M, Cole DEC, Hechtman P, Kaplan F, Modiano D, Moisan JP, Michalski R, Labuda D (2003) Haplotypes in the dystrophin DNA segment point to a mosaic origin of modern humans’ diversity. Am J Hum Genet 73:994–1015

    PubMed  Article  CAS  Google Scholar 

Download references

Acknowledgments

We are indebted to all individuals who provided samples for the analysis and to different colleagues who generously shared their DNA collections. Tina Wambach and Alan Lovell participated in the early stage of this project. This work was supported by grant from the Canadian Institutes of Health Research (MOP-67150 to DL).

Author information

Affiliations

Authors

Corresponding author

Correspondence to Damian Labuda.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM1 (DOC 772 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Yotova, V., Lefebvre, J., Kohany, O. et al. Tracing genetic history of modern humans using X-chromosome lineages. Hum Genet 122, 431 (2007). https://doi.org/10.1007/s00439-007-0413-4

Download citation

Keywords

  • African Population
  • Modern Human
  • Recent Common Ancestor
  • Mutation Scheme
  • Dystrophin Gene