The Y chromosome as a marker for the history and structure of human populations

This project, a Wellcome Trust Senior Fellowship in Basic Biomedical Science, ran from August 1999 to July 2004. Please see Pattern and process in human genetic diversity: from genomes to populations for information about my current Fellowship project.

The human Y chromosome determines maleness by causing the development of the testis. It is an unusual segment of the human genome since, apart from two small regions in which pairing and exchange take place with the X chromosome, it is male-specific and haploid, and escapes from recombination. These unique properties of the Y have important consequences for its mutation processes, its genes, and its population genetics: Y chromosomes pass down from father to son largely unchanged, except by the gradual accumulation of mutations. By examining the differences between modern Y chromosomes (as DNA polymorphisms) we can attempt to reconstruct a history of human paternal lineages (1). This complements maternal lineage studies using mitochondrial DNA and studies using biparentally inherited markers in the rest of the genome. Our interests lie in developing powerful new polymorphic marker systems, and applying these to questions of population structure and history, genealogy, forensics, and the investigation of selective influences on the Y chromosome.

We have isolated the first Y-specific minisatellite, MSY1, and designed a PCR-based assay system ('MVR-PCR') which yields digital DNA codes for Y chromosomes (2). MSY1 has very many alleles (useful in population genetic, forensic [3 - 5], and genealogical studies), and the structures of these suggest the action of remarkable and novel mutation processes in the evolution of the locus (6). MVR-PCR allows direct access to haploid mutation rates and processes through the analysis of mutants isolated from pedigrees and from sperm DNA. Other such loci may exist on the Y, and these are being sought.

We are applying MSY1, which has a mutation rate of a few percent per generation, together with less rapidly mutating systems (microsatellites: about 10-3 per generation; and base substitutions: about 10-8 per generation) in a hierarchical, or 'genealogical' approach to Y diversity. The slowly mutating markers define 'haplogroups' of chromosomes related by descent, and the microsatellites and minisatellite can then be used to examine diversity within these; mutation analysis at MSY1 provides a tool which should allow us to estimate ages for the most recent common ancestors of groups of chromosomes, as an alternative to microsatellites (7). MSY1 can also be used to interrogate indirectly the mutational properties of Y-specific microsatellites (8).

We have coordinated a large collaborative study to test hypotheses for the origins of modern European populations from a Y chromosome perspective (9, 10), interpreting patterns of diversity in terms of both the impact of the arrival of agriculture in Europe, and of linguistic and geographical barriers to gene flow. The distribution of European Y diversity is strongly clinal (9), including a major south-east/north-west component culminating in near fixation of one haplogroup in the west of Ireland (11), which is likely to reflect the movement of agriculturalists in the neolithic. Other clines have different foci and ranges, and probably reflect distinct, and more regional, population movements. Studies of Y-chromosomal diversity in Asia and the Middle-East also support a model of demic diffusion, of farmers from South-West Iran and nomads from western and central Asia, into India (12). Our current high resolution population studies are focusing on the colonisation of the Pacific (12), the genetic history of the Iberian peninsula (14), and the population histories of European Gypsies (15) and Ladin-speaking people of the Eastern Italian Alps.

We are also developing and analysing other kinds of polymorphisms, including Y-specific microsatellites, and base-substitutions and insertion-deletions (e.g. ref. 16). The latter class is not only of interest in diversity studies, but also in the understanding of the aetiology of male infertility, which can be caused by deletion of Y-chromosomal genes involved in spermatogenesis (17, 18). Particular sub-sets of Y chromosomes may predispose to infertility, or to male-specific cancers, and thus it may be possible to identify the influence of selection on Y haplotypes (19 - 21), as we have done for one class of XX male (22).

In many societies, Y chromosomes and surnames are coinherited, and the hypervariable markers we are developing have potential as tools for the reliable detection of patrilineal relationships over many generations (23); this potential is currently being tested, and has been applied in a study of the paternity of the putative sons of Thomas Jefferson, third president of the United States (24).


1. Jobling, M.A. and Tyler-Smith, C. (1995) Fathers and sons: the Y chromosome and human evolution. Trends Genet. 11, 449-456.

2. Jobling, M.A., Bouzekri, N. and Taylor, P.G. (1998) Hypervariable digital DNA codes for human paternal lineages: MVR-PCR at the Y-specific minisatellite, MSY1 (DYF155S1). Hum. Mol. Genet. 7, 643-653.

3. Jobling, M.A., Pandya, A. and Tyler-Smith, C. (1997) The Y chromosome in forensic analysis and paternity testing. Int. J. Legal Med. 110, 118-124.

4. Jobling, M.A. (2001) Y-chromosomal SNP haplotype diversity in forensic analysis. Forens. Sci. Internat. 118, 162-172.

5. Roewer L., Krawczak, M., Willuweit, S., Nagy, M., Alves, C., Amorim, A., Anslinger, K., Augustin, C., Betz, A., Bosch, E., Caglià, A., Carracedo, A., Corach, D., Dobosz, T., Dupuy, B.M., Füredi, S., Gehrig, C., Gusmaõ, L., Henke, J., Henke, L., Hidding, M., Hohoff, C., Hoste, B., Jobling, M.A., Kärgel, H.J., de Knijff, P., Lessig, R., Liebeherr, E., Lorente, M., Martínez-Jarreta, B., Nievas, P., Nowak, M., Parson, W., Pascali, V.L., Penacino, G., Ploski, R., Rolf, B., Sala, A., Schmidt, U., Schmitt, C., Schneider, P.M., Szibor, R., Teifel-Greding, J. and Kayser, M. (2001) Online reference database of European Y-chromosomal short tandem repeat (STR) haplotypes. Forens. Sci. Internat. 118, 103-111.

6. Bouzekri, N., Taylor, P.G., Hammer, M.F. and Jobling, M.A. (1998) Novel mutation processes in the evolution of a haploid minisatellite, MSY1: array homogenization without homogenization. Hum. Mol. Genet. 7, 655-659.

7. Zerjal, T., Dashnyam, B., Pandya, A., Kayser, M., Roewer, L., Santos, F.R., Schiefenhövel, W., Fretwell, N., Jobling, M.A., Harihara, S., Shimizu, K., Semjidmaa, D., Sajantila, A., Salo, P., Crawford, M.H., Ginter, E.K., Evgrafov, O.V. and Tyler-Smith, C. (1997) Genetic relationships of Asians and northern Europeans, revealed by Y-chromosomal DNA analysis. Am. J. Hum. Genet. 60, 1174-1183.

8. Jobling, M.A., Heyer, E., Dieltjes, P. and de Knijff, P. (1999) Y-chromosome- specific microsatellite mutation rates re-examined using a minisatellite, MSY1. Hum. Mol. Genet. 8, 2117-2120.

9. Rosser, Z.H., Zerjal, T., Hurles, M.E., Adojaan, M., Alavantic, D., Amorim, A., Amos, W., Armenteros, M., Arroyo, E., Barbujani, G., Beckman, G., Beckman, L., Bertranpetit, J., Bosch, E., Bradley, D.G., Brede, G., Cooper, G., C˘rte-Real, H.B.S.M., de Knijff, P., Decorte, R., Dubrova, Y.E., Evgrafov, O., Gilissen, A., Glisic, S., G÷lge, M., Hill, E.W., Jeziorowska, A., Kalaydjieva, L., Kayser, M., Kivisild, T., Kravchenko, S. A., Krumina, A., Kucinskas, V., Lavinha, J., Livshits, L. A., Malaspina, P., Maria, S., McElreavey, K., Meitinger, T.A., Mikelsaar, A.-V., Mitchell, R. J., Nafa, K., Nicholson, J., N°rby, S., Pandya, A., Parik, J., Patsalis, P.C., Pereira, L., Peterlin, B., Pielberg, G., Prata, M.J., PreviderÚ, C., Roewer, L., Rootsi, S., Rubinsztein, D. C., Saillard, J., Santos, F.R., Stefanescu, G., Sykes, B.C., Tolun, A., Villems, R., Tyler-Smith C. and Jobling, M.A. (2000) Y-chromosomal diversity in Europe is clinal and influenced primarily by geography, rather than by language. Am. J. Hum. Genet. 67, 1526-1543.

10. Pereira, L., Dupanloup de Ceuninck, I., Rosser, Z.H., Jobling, M.A. and Barbujani, G. (2001) Y-chromosome mismatch distributions in Europe. Mol. Biol. Evol. 18, 1259-1271.

11. Hill, E.W., Jobling, M.A. and Bradley, D.G. (2000) Y-chromosome variation and Irish origins. Nature 404, 351-352.

12. Quintana-Murci, L., Krausz, C., Zerjal, T., Sayar, S.H., Hammer, M.F., Mehdi, S.Q., Ayub, Q., Qamar, R., Mohyuddin, A., Radhakrishna, U., Jobling, M.A., Tyler-Smith, C., and Ken McElreavey (2001) Y-Chromosome lineages trace diffusion of people and languages in Southwestern Asia. Am. J. Hum. Genet. 68, 537-542.

13. Hurles, M.E., Irven, C., Nicholson, J., Taylor, P.G., Santos, F.R., Loughlin, J., Jobling, M.A. and Sykes, B.C. (1998) European Y-chromosomal lineages in Polynesia: a contrast to the population structure revealed by mitochondrial DNA. Am. J. Hum. Genet. 63, 1793-1806.

14. Hurles, M.E., Veitia, R., Arroyo, E., Armenteros, M., Bertranpetit, J., Pérez-Lezaun, A., Bosch, E., Shlumukova, M., Cambon-Thomsen, A., McElreavey, K., López de Munain, A., Röhl, A., Wilson, I.J., Singh, L., Pandya, A., Santos, F.R., Tyler-Smith, C. and Jobling, M.A. (1999) Recent male-mediated gene flow over a linguistic barrier in Iberia, suggested by analysis of a Y-chromosomal DNA polymorphism. Am. J. Hum. Genet. 65, 1437-1448.

15. Kalaydjieva, L., Calafell, F., Jobling, M.A., Angelicheva, D., de Knijff, P., Rosser, Z.H., Hurles, M.E., Underhill, P., Tournev, I., Marushiakova, E. and Popov, V. (2001) Patterns of inter- and intra-group genetic diversity in the Vlax Roma as revealed by Y chromosome and mitochondrial DNA lineages. Eur. J. Hum. Genet. 9, 97-104.

16. Jobling, M.A., Samara, V., Pandya, A., Fretwell, N., Bernasconi, B., Mitchell, R.J., Gerelsaikhan, T., Dashnyam, B., Sajantila, A., Salo, P.J., Nakahori, Y., Disteche, C.M., Thangaraj, K., Singh, L., Crawford, M.H. and Tyler-Smith, C. (1996) Recurrent duplication and deletion polymorphisms on the long arm of the Y chromosome in normal males.Hum. Mol. Genet. 5, 1767-1775.

17. Ma, K., Inglis, J.D., Sharkey, A., Bickmore, W.A., Hill, R.E., Prosser, E.J., Speed, R.M., Thomson, E.J., Jobling, M., Taylor, K., Wolfe, J., Cooke, H.J., Hargreave, T.B. and Chandley, A.C. (1993) A Y chromosome gene family with RNA-binding protein homology - candidates for the azoospermia factor AZF controlling human spermatogenesis. Cell 75, 1287-1295.

18. Blanco, P., Shlumukova, M., Sargent, C.A., Jobling, M.A., Affara, N. and Hurles, M.E. (2000) Divergent outcomes of intra-chromosomal recombination on the human Y chromosome: male infertility and recurrent polymorphism. J. Med. Genet. 37, 752-758.

19. Jobling, M.A. and Tyler-Smith, C. (2000) New uses for new haplotypes: the human Y chromosome, disease and selection. Trends Genet. 16, 356-362.

20. Quintana-Murci, L., Krausz, C., Heyer, E., Gromoll, J., Seifer, I., Barton, D.E., Barrett, T., Skakkebaek, N.E., Rajpert-De Meyts, E., Mitchell, M., Lee, A.C., Jobling, M.A. and McElreavey, K. (2001) The relationship between Y chromosome DNA haplotypes and Y chromosome deletions leading to male infertility. Hum. Genet., 108, 55-58.

21. Krausz, C. Quintana-Murci, L., Rajpert-De Meyts, E., J°rgensen, N., Jobling, M.A., Rosser, Z.H., Skakkebaek, N.E. and McElreavey, K. (2001) Hum. Mol. Genet. 10, 1873-1877. Identification of a Y chromosome haplogroup associated with reduced sperm counts.

22. Jobling, M.A., Williams, G., Schiebel, K., Pandya, A., McElreavey, K., Salas, L., Rappold, G.A., Affara, N.A. and Tyler-Smith, C. (1998) A selective difference between human Y-chromosomal DNA haplotypes. Curr. Biol. 8, 1391-1394.

23. Jobling, M.A. (2001) In the name of the father: surnames and genetics. Trends Genet. 17, 353-357.

24. Foster, E.A., Jobling, M.A., Taylor, P.G., Donnelly, P., de Knijff, P., Mieremet, R., Zerjal, T. and Tyler-Smith, C. (1998) Jefferson fathered slave's last child. Nature 396, 27-28.

If you are interested in the Jefferson/Hemings case, visit the Monticello website, where a detailed report is available.


This project is funded by the Wellcome Trust.

[University Home] [Faculty of Medicine and Biological Sciences Home] [Department of Genetics Home] [Staff member home page] [University Index A-Z][University Search][University Help]

Last updated: 16th December 2004
Mark Jobling
The views expressed in this document are those of the document owner. The University of Leicester is not responsible for the content of external Internet sites, and does not endorse opinions expressed or services provided at those sites.