As a consequence of its key role in male sex determination, the Y chromosome has unique genetic properties that lead to it carrying highly informative haplotypes that evolve largely through the simple accumulation of mutations.
Advances in technology have allowed ~10 Mb of Y-chromosome DNA to be sequenced from large population samples, with consequent unbiased ascertainment of their genetic variation.
Y-Chromosome sequences can be assembled into a robust phylogeny, which can be calibrated using estimates of the mutation rate from family studies, known archaeological events or ancient DNA samples.
The calibrated Y-chromosome phylogeny reveals male expansions corresponding to the migration of modern humans out of Africa ~60,000 years ago, the colonization of the Americas ~15,000 years ago and more recent technology-driven population expansions.
The Y chromosome has a particularly important role in forensic genetics, as it allows male-specific DNA profiles to be compared at an increasingly high resolution.
In genealogical studies, the male-line inheritance of the Y chromosome makes it a perfect tool for studies of male family history, which has led to a burgeoning area of citizen science.
The Y chromosome is central to disorders of sex determination and spermatogenesis. Recently, mosaic somatic loss of the Y chromosome in ageing men has been associated with an increased risk of cancer mortality and Alzheimer disease.
The properties of the human Y chromosome – namely, male specificity, haploidy and escape from crossing over — make it an unusual component of the genome, and have led to its genetic variation becoming a key part of studies of human evolution, population history, genealogy, forensics and male medical genetics. Next-generation sequencing (NGS) technologies have driven recent progress in these areas. In particular, NGS has yielded direct estimates of mutation rates, and an unbiased and calibrated molecular phylogeny that has unprecedented detail. Moreover, the availability of direct-to-consumer NGS services is fuelling a rise of 'citizen scientists', whose interest in resequencing their own Y chromosomes is generating a wealth of new data.
This is a preview of subscription content
Subscribe to Nature+
Get immediate online access to the entire Nature family of 50+ journals
Subscribe to Journal
Get full journal access for 1 year
only $4.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Bachtrog, D. Y-Chromosome evolution: emerging insights into processes of Y-chromosome degeneration. Nat. Rev. Genet. 14, 113–124 (2013).
Repping, S. et al. High mutation rates have driven extensive structural polymorphism among human Y chromosomes. Nat. Genet. 38, 463–467 (2006).
Jobling, M. A. Copy number variation on the human Y chromosome. Cytogenet. Genome Res. 123, 253–262 (2008).
Poznik, G. D. et al. Punctuated bursts in human male demography inferred from 1,244 worldwide Y-chromosome sequences. Nat. Genet. 48, 593–599 (2016). This is the largest sequence-based study of Y-chromosome variation to be carried out thus far, and includes SNPs, STRs, indels, multiple nucleotide polymorphisms and CNVs; the data, DNA and cell lines are publicly available.
Heyer, E., Chaix, R., Pavard, S. & Austerlitz, F. Sex-specific demographic behaviours that shape human genomic variation. Mol. Ecol. 21, 597–612 (2012).
Jobling, M. A., Pandya, A. & Tyler-Smith, C. The Y chromosome in forensic analysis and paternity testing. Int. J. Legal Med. 110, 118–124 (1997).
Calafell, F. & Larmuseau, M. H. The Y chromosome as the most popular marker in genetic genealogy benefits interdisciplinary research. Hum. Genet. 136, 559–573 (2017).
Ober, C., Loisel, D. A. & Gilad, Y. Sex-specific genetic architecture of human disease. Nat. Rev. Genet. 9, 911–922 (2008).
McElreavey, K., Ravel, C., Chantot-Bastaraud, S. & Siffroi, J. P. Y chromosome variants and male reproductive function. Int. J. Androl. 29, 298–303 (2006).
Forsberg, L. A., Gisselsson, D. & Dumanski, J. P. Mosaicism in health and disease — clones picking up speed. Nat. Rev. Genet. 18, 128–142 (2016).
Jobling, M. A. & Tyler-Smith, C. The human Y chromosome: an evolutionary marker comes of age. Nat. Rev. Genet. 4, 598–612 (2003).
Y Chromosome Consortium. A nomenclature system for the tree of human Y-chromosomal binary haplogroups. Genome Res. 12, 339–348 (2002).
de Knijff, P. Messages through bottlenecks: on the combined use of slow and fast evolving polymorphic markers on the human Y chromosome. Am. J. Hum. Genet. 67, 1055–1061 (2000).
Zerjal, T. et al. Genetic relationships of Asians and northern Europeans, revealed by Y-chromosomal DNA analysis. Am. J. Hum. Genet. 60, 1174–1183 (1997).
Heyer, E., Puymirat, J., Dieltjes, P., Bakker, E. & de Knijff, P. Estimating Y chromosome specific microsatellite mutation frequencies using deep rooting pedigrees. Hum. Mol. Genet. 6, 799–803 (1997).
Zhivotovsky, L. A. et al. The effective mutation rate at Y chromosome short tandem repeats, with application to human population-divergence time. Am. J. Hum. Genet. 74, 50–61 (2004).
Hammer, M. F. A recent common ancestry for human Y chromosomes. Nature 378, 376–378 (1995).
Whitfield, L. S., Hawkins, T. L., Goodfellow, P. N. & Sulston, J. 41 kilobases of analyzed sequence from the pseudoautosomal and sex-determining regions of the short arm of the human Y chromosome. Genomics 27, 306–311 (1995).
Hinds, D. A. et al. Whole-genome patterns of common DNA variation in three human populations. Science 307, 1072–1079 (2005).
1000 Genomes Project Consortium et al. A map of human genome variation from population-scale sequencing. Nature 467, 1061–1073 (2010).
Skaletsky, H. et al. The male-specific region of the human Y chromosome: a mosaic of discrete sequence classes. Nature 423, 825–837 (2003).
Yan, S. et al. Y chromosomes of 40% Chinese descend from three Neolithic super-grandfathers. PLoS ONE 9, e105691 (2014).
Lippold, S. et al. Human paternal and maternal demographic histories: insights from high-resolution Y chromosome and mtDNA sequences. Investig. Genet. 5, 13 (2014).
Hallast, P. et al. The Y-chromosome tree bursts into leaf: 13,000 high-confidence SNPs covering the majority of known clades. Mol. Biol. Evol. 32, 661–673 (2015). This large-scale sequence-based study of Y-chromosome variation compares Y-SNP-based and Y-STR-based approaches to estimate the ages of lineages.
Wei, W. et al. A calibrated human Y-chromosomal phylogeny based on resequencing. Genome Res. 23, 388–395 (2013). This is the first study of Y-chromosome phylogeny to be based on high-coverage sequencing and reveals the rapid expansion of Y lineages around the time of the expansion of modern humans out of Africa.
Poznik, G. D. et al. Sequencing Y chromosomes resolves discrepancy in time to common ancestor of males versus females. Science 341, 562–565 (2013).
Karmin, M. et al. A recent bottleneck of Y chromosome diversity coincides with a global change in culture. Genome Res. 25, 459–466 (2015). This large-scale sequence-based study of Y-chromosome variation reports that a strong Y-chromosome, but not mtDNA, bottleneck occurred within the past 10,000 years.
Francalacci, P. et al. Low-pass DNA sequencing of 1200 Sardinians reconstructs European Y-chromosome phylogeny. Science 341, 565–569 (2013).
Willems, T. et al. Population-scale sequencing data enable precise estimates of Y-STR mutation rates. Am. J. Hum. Genet. 98, 919–933 (2016).
Redon, R. et al. Global variation in copy number in the human genome. Nature 444, 444–454 (2006).
Espinosa, J. R., Ayub, Q., Chen, Y., Xue, Y. & Tyler-Smith, C. Structural variation on the human Y chromosome from population-scale resequencing. Croat. Med. J. 56, 194–207 (2015).
Massaia, A. & Xue, Y. Human Y chromosome copy number variation in the next generation sequencing era and beyond. Hum. Genet. 136, 591–603 (2017).
Scozzari, R. et al. An unbiased resource of novel SNP markers provides a new chronology for the human Y chromosome and reveals a deep phylogenetic structure in Africa. Genome Res. 24, 535–544 (2014).
Balanovsky, O. et al. Deep phylogenetic analysis of haplogroup G1 provides estimates of SNP and STR mutation rates on the human Y-chromosome and reveals migrations of Iranic speakers. PLoS ONE 10, e0122968 (2015).
Helgason, A. et al. The Y-chromosome point mutation rate in humans. Nat. Genet. 47, 453–457 (2015). This is the largest family-based study of the Y-SNP mutation rate to be carried out so far and benefits from the analysis of deep-rooting Icelandic pedigrees.
Mendez, F. L. et al. An African American paternal lineage adds an extremely ancient root to the human Y chromosome phylogenetic tree. Am. J. Hum. Genet. 92, 454–459 (2013).
Xue, Y. et al. Human Y chromosome base-substitution mutation rate measured by direct sequencing in a deep-rooting pedigree. Curr. Biol. 19, 1453–1457 (2009).
Fu, Q. et al. Genome sequence of a 45,000-year-old modern human from western Siberia. Nature 514, 445–449 (2014).
Kivisild, T. The study of human Y chromosome variation through ancient DNA. Hum. Genet. 136, 529–546 (2017).
Moorjani, P., Gao, Z. & Przeworski, M. Human germline mutation and the erratic evolutionary clock. PLoS Biol. 14, e2000744 (2016).
Mendez, F. L., Poznik, G. D., Castellano, S. & Bustamante, C. D. The divergence of Neandertal and modern human Y chromosomes. Am. J. Hum. Genet. 98, 728–734 (2016). This study estimates that the divergence between Neanderthal and modern human Y chromosomes occurred ~590 kya, which is consistent with the divergence time of the two populations.
Veeramah, K. R. & Hammer, M. F. The impact of whole-genome sequencing on the reconstruction of human population history. Nat. Rev. Genet. 15, 149–162 (2014).
Underhill, P. A. & Kivisild, T. Use of Y chromosome and mitochondrial DNA population structure in tracing human migrations. Annu. Rev. Genet. 41, 539–564 (2007).
Brown, G. R., Laland, K. N. & Mulder, M. B. Bateman's principles and human sex roles. Trends Ecol. Evol. 24, 297–304 (2009).
Batini, C. & Jobling, M. A. Detecting past male-mediated expansions using the Y chromosome. Hum. Genet. 136, 547–557 (2017).
Zerjal, T. et al. The genetic legacy of the Mongols. Am. J. Hum. Genet. 72, 717–721 (2003).
Xue, Y. et al. Recent spread of a Y-chromosomal lineage in northern China and Mongolia. Am. J. Hum. Genet. 77, 1112–1116 (2005).
Moore, L. T., McEvoy, B., Cape, E., Simms, K. & Bradley, D. G. A Y-chromosome signature of hegemony in Gaelic Ireland. Am. J. Hum. Genet. 78, 334–338 (2006).
Burton, M. L. et al. Regions based on social structure. Curr. Anthropol. 37, 87–123 (1996).
Murdock, G. P. Ethnographic Atlas (Univ. of Pittsburgh Press, 1967).
Seielstad, M. T., Minch, E. & Cavalli-Sforza, L. L. Genetic evidence for a higher female migration rate in humans. Nat. Genet. 20, 278–280 (1998).
Oota, H., Settheetham-Ishida, W., Tiwawech, D., Ishida, T. & Stoneking, M. Human mtDNA and Y-chromosome variation is correlated with matrilocal versus patrilocal residence. Nat. Genet. 29, 20–21 (2001).
Wilkins, J. F. Unraveling male and female histories from human genetic data. Curr. Opin. Genet. Dev. 16, 611–617 (2006).
Alves-Silva, J. et al. The ancestry of Brazilian mtDNA lineages. Am. J. Hum. Genet. 67, 444–461 (2000).
Rojas, W. et al. Genetic make up and structure of Colombian populations by means of uniparental and biparental DNA markers. Am. J. Phys. Anthropol. 143, 13–20 (2010).
Corach, D. et al. Inferring continental ancestry of Argentineans from autosomal, Y-chromosomal and mitochondrial DNA. Ann. Hum. Genet. 74, 65–76 (2010).
Redd, A. J. et al. Gene flow from the Indian subcontinent to Australia: evidence from the Y chromosome. Curr. Biol. 12, 673–677 (2002).
Bergstrom, A. et al. Deep roots for Aboriginal Australian Y chromosomes. Curr. Biol. 26, 809–813 (2016).
Wei, W., Ayub, Q., Xue, Y. & Tyler-Smith, C. A comparison of Y-chromosomal lineage dating using either resequencing or Y-SNP plus Y-STR genotyping. Forensic Sci. Int. Genet. 7, 568–572 (2013).
Ilumae, A. M. et al. Human Y chromosome haplogroup N: a non-trivial time-resolved phylogeography that cuts across language families. Am. J. Hum. Genet. 99, 163–173 (2016).
Batini, C. et al. Large-scale recent expansion of European patrilineages shown by population resequencing. Nat. Commun. 6, 7152 (2015).
Balaresque, P. et al. A predominantly Neolithic origin for European paternal lineages. PLoS Biol. 8, e1000285 (2010).
Allentoft, M. E. et al. Population genomics of Bronze Age Eurasia. Nature 522, 167–172 (2015).
Haak, W. et al. Massive migration from the steppe was a source for Indo-European languages in Europe. Nature 522, 207–211 (2015).
Foster, E. A. et al. Jefferson fathered slave's last child. Nature 396, 27–28 (1998).
King, T. E. & Jobling, M. A. Founders, drift and infidelity: the relationship between Y chromosome diversity and patrilineal surnames. Mol. Biol. Evol. 26, 1093–1102 (2009).
Martinez-Cadenas, C. et al. The relationship between surname frequency and Y chromosome variation in Spain. Eur. J. Hum. Genet. 24, 120–128 (2016).
Sole-Morata, N., Bertranpetit, J., Comas, D. & Calafell, F. Y-Chromosome diversity in Catalan surname samples: insights into surname origin and frequency. Eur. J. Hum. Genet. 23, 1549–1557 (2015).
McEvoy, B. & Bradley, D. G. Y-Chromosomes and the extent of patrilineal ancestry in Irish surnames. Hum. Genet. 119, 212–219 (2006).
Greeff, J. M. & Erasmus, J. C. Three hundred years of low non-paternity in a human population. Heredity 115, 396–404 (2015).
Larmuseau, M. H. et al. Low historical rates of cuckoldry in a Western European human population traced by Y-chromosome and genealogical data. Proc. Biol. Sci. 280, 20132400 (2013).
King, T. E., Ballereau, S. J., Schürer, K. & Jobling, M. A. Genetic signatures of coancestry within surnames. Curr. Biol. 16, 384–388 (2006).
Gymrek, M., McGuire, A. L., Golan, D., Halperin, E. & Erlich, Y. Identifying personal genomes by surname inference. Science 339, 321–324 (2013).
King, T. E. & Jobling, M. A. What's in a name? Y chromosomes, surnames and the genetic genealogy revolution. Trends Genet. 25, 351–360 (2009).
Rocca, R. A. et al. Discovery of Western European R1b1a2 Y chromosome variants in 1000 genomes project data: an online community approach. PLoS ONE 7, e41634 (2012).
Balanovsky, O. et al. Phylogeography of human Y-chromosome haplogroup Q3-L275 from an academic/citizen science collaboration. BMC Evol. Biol. 17, 18 (2017).
Sinclair, A. H. et al. A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature 346, 240–244 (1990).
Berta, P. et al. Genetic evidence equating SRY and the testis-determining factor. Nature 348, 448–450 (1990).
Vogt, P. H. et al. Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11. Hum. Mol. Genet. 5, 933–943 (1996).
Tyler-Smith, C. & Krausz, C. The will-o'-the-wisp of genetics — hunting for the azoospermia factor gene. N. Engl. J. Med. 360, 925–927 (2009).
Ramathal, C. et al. DDX3Y gene rescue of a Y chromosome AZFa deletion restores germ cell formation and transcriptional programs. Sci. Rep. 5, 15041 (2015).
Wang, Q. J. et al. Y-Linked inheritance of non-syndromic hearing impairment in a large Chinese family. J. Med. Genet. 41, E80 (2004).
Wang, Q. et al. Genetic basis of Y-linked hearing impairment. Am. J. Hum. Genet. 92, 301–306 (2013). This study reports the genetic investigation of the only simple heritable disorder that has thus far been mapped to the Y chromosome. It shows that this disorder is caused by an insertion of DNA from chromosome 1 and demonstrates why simple Y-linked genetic disorders are so rare.
Charchar, F. J. et al. Inheritance of coronary artery disease in men: an analysis of the role of the Y chromosome. Lancet 379, 915–922 (2012).
Giachini, C. et al. TSPY1 copy number variation influences spermatogenesis and shows differences among Y lineages. J. Clin. Endocrinol. Metab. 94, 4016–4022 (2009).
Shen, Y. et al. A significant effect of the TSPY1 copy number on spermatogenesis efficiency and the phenotypic expression of the gr/gr deletion. Hum. Mol. Genet. 22, 1679–1695 (2013).
Giachini, C. et al. Partial AZFc deletions and duplications: clinical correlates in the Italian population. Hum. Genet. 124, 399–410 (2008).
Rozen, S. G. et al. AZFc deletions and spermatogenic failure: a population-based survey of 20,000 Y chromosomes. Am. J. Hum. Genet. 91, 890–896 (2012). This is the largest study to date that has investigated Y-chromosome deletions in men who were not ascertained on the basis of spermatogenic failure and reports that a deletion of some kind is present in 1 in 27 men.
Sato, Y. et al. Y chromosome gr/gr subdeletion is associated with lower semen quality in young men from the general Japanese population but not in fertile Japanese men. Biol. Reprod. 90, 116 (2014).
Nathanson, K. L. et al. The Y deletion gr/gr and susceptibility to testicular germ cell tumor. Am. J. Hum. Genet. 77, 1034–1043 (2005).
Printzlau, F., Wolstencroft, J. & Skuse, D. H. Cognitive, behavioral, and neural consequences of sex chromosome aneuploidy. J. Neurosci. Res. 95, 311–319 (2017).
Schoemaker, M. J. et al. Mortality in women with Turner syndrome in Great Britain: a national cohort study. J. Clin. Endocrinol. Metab. 93, 4735–4742 (2008).
Higgins, C. D., Swerdlow, A. J., Schoemaker, M. J., Wright, A. F. & Jacobs, P. A. Mortality and cancer incidence in males with Y polysomy in Britain: a cohort study. Hum. Genet. 121, 691–696 (2007).
Fisher, E. M. C. et al. Homologous ribosomal protein genes on the human X and Y chromosomes: escape from inactivation and possible implications for Turner syndrome. Cell 63, 1205–1218 (1990).
Jacobs, P. A., Brunton, M., Court Brown, W. M., Doll, R. & Goldstein, H. Change of human chromosome count distribution with age: evidence for a sex differences. Nature 197, 1080–1081 (1963).
Forsberg, L. A. et al. Mosaic loss of chromosome Y in peripheral blood is associated with shorter survival and higher risk of cancer. Nat. Genet. 46, 624–628 (2014). This is the study that reinvigorated investigation of the medical consequences of somatic loss of the Y chromosome in ageing men.
Dumanski, J. P. et al. Mutagenesis. Smoking is associated with mosaic loss of chromosome Y. Science 347, 81–83 (2015).
Dumanski, J. P. et al. Mosaic loss of chromosome Y in blood is associated with Alzheimer disease. Am. J. Hum. Genet. 98, 1208–1219 (2016).
Ganster, C. et al. New data shed light on Y-loss-related pathogenesis in myelodysplastic syndromes. Genes Chromosomes Cancer 54, 717–724 (2015).
Noveski, P. et al. Loss of Y chromosome in peripheral blood of colorectal and prostate cancer patients. PLoS ONE 11, e0146264 (2016).
Zhou, W. et al. Mosaic loss of chromosome Y is associated with common variation near TCL1A. Nat. Genet. 48, 563–568 (2016).
Wright, D. J. et al. Genetic variants associated with mosaic Y chromosome loss highlight cell cycle genes and overlap with cancer susceptibility. Nat. Genet. 49, 674–679 (2017).
Wong, H. Y. et al. TMSB4Y is a candidate tumor suppressor on the Y chromosome and is deleted in male breast cancer. Oncotarget 6, 44927–44940 (2015).
Santos, F. R., Pandya, A. & Tyler-Smith, C. Reliability of DNA-based sex tests. Nat. Genet. 18, 103 (1998).
Jobling, M. A. et al. Structural variation on the short arm of the human Y chromosome: recurrent multigene deletions encompassing Amelogenin Y. Hum. Mol. Genet. 16, 307–316 (2007).
Wei, W. et al. Copy number variation in the human Y chromosome in the UK population. Hum. Genet. 134, 789–800 (2015).
Fernandes, S. et al. A large AZFc deletion removes DAZ3/DAZ4 and nearby genes from men in Y haplogroup N. Am. J. Hum. Genet. 74, 180–187 (2004).
Repping, S. et al. A family of human Y chromosomes has dispersed throughout northern Eurasia despite a 1.8-Mb deletion in the azoospermia factor c region. Genomics 83, 1046–1052 (2004).
Wilson Sayres, M. A., Lohmueller, K. E. & Nielsen, R. Natural selection reduced diversity on human Y chromosomes. PLoS Genet. 10, e1004064 (2014).
Rozen, S., Marszalek, J. D., Alagappan, R. K., Skaletsky, H. & Page, D. C. Remarkably little variation in proteins encoded by the Y chromosome's single-copy genes, implying effective purifying selection. Am. J. Hum. Genet. 85, 923–928 (2009).
Jobling, M. A. et al. A selective difference between human Y-chromosomal DNA haplotypes. Curr. Biol. 8, 1391–1394 (1998).
Goodwin, S., McPherson, J. D. & McCombie, W. R. Coming of age: ten years of next-generation sequencing technologies. Nat. Rev. Genet. 17, 333–351 (2016).
Chaisson, M. J., Wilson, R. K. & Eichler, E. E. Genetic variation and the de novo assembly of human genomes. Nat. Rev. Genet. 16, 627–640 (2015).
Haber, M., Mezzavilla, M., Xue, Y. & Tyler-Smith, C. Ancient DNA and the rewriting of human history: be sparing with Occam's razor. Genome Biol. 17, 1 (2016).
Balanovsky, O. et al. Genetic differentiation between upland and lowland populations shapes the Y-chromosomal landscape of West Asia. Hum. Genet. 36, 437–450 (2017).
Wise, A. L., Gyi, L. & Manolio, T. A. eXclusion: toward integrating the X chromosome in genome-wide association analyses. Am. J. Hum. Genet. 92, 643–647 (2013).
Ledford, H. AstraZeneca launches project to sequence 2 million genomes. Nature 532, 427 (2016).
Marx, V. The DNA of a nation. Nature 524, 503–505 (2015).
Sekido, R. & Lovell-Badge, R. Sex determination involves synergistic action of SRY and SF1 on a specific Sox9 enhancer. Nature 453, 930–934 (2008).
Cortez, D. et al. Origins and functional evolution of Y chromosomes across mammals. Nature 508, 488–493 (2014).
Lahn, B. T. & Page, D. C. Four evolutionary strata on the human X chromosome. Science 286, 964–967 (1999).
Page, D. C., Harper, M. E., Love, J. & Botstein, D. Occurrence of a transposition from the X-chromosome long arm to the Y-chromosome short arm during human evolution. Nature 311, 119–122 (1984).
Repping, S. et al. Polymorphism for a 1.6-Mb deletion of the human Y chromosome persists through balance between recurrent mutation and haploid selection. Nat. Genet. 35, 247–251 (2003).
Ross, M. T. et al. The DNA sequence of the human X chromosome. Nature 434, 325–337 (2005).
Rozen, S. et al. Abundant gene conversion between arms of massive palindromes in human and ape Y chromosomes. Nature 423, 873–876 (2003).
Hallast, P., Balaresque, P., Bowden, G. R., Ballereau, S. J. & Jobling, M. A. Recombination dynamics of a human Y-chromosomal palindrome: rapid GC-biased gene conversion, multi-kilobase conversion tracts, and rare inversions. PLoS Genet. 9, e1003666 (2013).
Balaresque, P. et al. Gene conversion violates the stepwise mutation model for microsatellites in Y-chromosomal palindromic repeats. Hum. Mutat. 35, 609–617 (2014).
Trombetta, B., Cruciani, F., Underhill, P. A., Sellitto, D. & Scozzari, R. Footprints of X-to-Y gene conversion in recent human evolution. Mol. Biol. Evol. 27, 714–725 (2010).
Rosser, Z. H., Balaresque, P. & Jobling, M. A. Gene conversion between the X chromosome and the male-specific region of the Y chromosome at a translocation hotspot. Am. J. Hum. Genet. 85, 130–134 (2009).
Trombetta, B., Sellitto, D., Scozzari, R. & Cruciani, F. Inter- and intraspecies phylogenetic analyses reveal extensive X–Y gene conversion in the evolution of gametologous sequences of human sex chromosomes. Mol. Biol. Evol. 31, 2108–2123 (2014).
Berg, I. L. et al. PRDM9 variation strongly influences recombination hot-spot activity and meiotic instability in humans. Nat. Genet. 42, 859–863 (2010).
Crow, J. F. The origins, patterns and implications of human spontaneous mutation. Nat. Rev. Genet. 1, 40–47 (2000).
Segurel, L., Wyman, M. J. & Przeworski, M. Determinants of mutation rate variation in the human germline. Annu. Rev. Genomics Hum. Genet. 15, 47–70 (2014).
Kayser, M. Forensic use of Y-chromosome DNA: a general overview. Hum. Genet. 136, 621–635 (2017).
Prinz, M., Ishii, A., Coleman, A., Baum, H. J. & Shaler, R. C. Validation and casework application of a Y chromosome specific STR multiplex. Forensic Sci. Int. 120, 177–188 (2001).
Ballantyne, K. N. et al. Mutability of Y-chromosomal microsatellites: rates, characteristics, molecular bases, and forensic implications. Am. J. Hum. Genet. 87, 341–353 (2010).
Ballantyne, K. N. et al. A new future of forensic Y-chromosome analysis: rapidly mutating Y-STRs for differentiating male relatives and paternal lineages. Forensic Sci. Int. Genet. 6, 208–218 (2012).
1000 Genomes Project Consortium et al. A global reference for human genetic variation. Nature 526, 68–74 (2015).
C.T.-S. is supported by a grant from the Wellcome Trust (grant number 098051).
The authors declare no competing financial interests.
The state of having one chromosome copy per cell.
- Short tandem repeats
(STRs). DNA sequences that contain a number (usually ≤50) of tandemly repeated short (2–6 bp) sequences, such as (GATA)n. The sequences are often polymorphic and are also known as microsatellites.
Related sets of Y chromosomes that are collectively defined by specific, slowly mutating binary polymorphisms (usually single-nucleotide polymorphisms).
A tree-like diagram that represents the evolutionary relationships among a set of sequences.
- Maximum parsimony
A method for selecting the best evolutionary tree from a set of alternatives on the basis of which contains the fewest mutational changes.
- Ascertainment bias
Bias in a dataset caused by the way that DNA sequence variants are identified or samples are collected.
The analysis of the geographical distributions of different clades within a phylogeny, such as haplogroups in the Y-chromosome phylogeny.
A highly condensed, transcriptionally inert segment of the genome that is often composed of repeated DNA sequences. On the Y chromosome, heterochromatin is found mainly near the centromere and in the distal half of the long arm.
The part of the genome that is in an extended conformation and contains transcriptionally active DNA.
Describes a DNA sequence in which reliable genotype calls can be made in next-generation sequencing because of the unambiguous mapping of reads to the reference sequence.
Similar sequences on the X and Y chromosomes that share an origin in the ancestral autosomal pair from which the current X and Y chromosomes have evolved.
- Gene conversion
A nonreciprocal exchange of sequence information between one DNA molecule and another. Non-allelic gene conversion is active between repeated sequences on the Y chromosome.
DNA sequences that contain a variable number (from ~10 to >1,000) of tandemly arranged repeat units that are each typically 10–100 bp in length.
Short regions of the genome (a few kilobases in length) in which meiotic crossing over is significantly increased above the genome average.
Taking a particular known sequence from an existing source, or an entire genome, and determining the equivalent sequence in several different individuals as a means by which to discover sequence variation.
A lineage or species that is more distantly related to a group of lineages or species than any of them is to each other.
The mixing of distinct parental populations resulting in a new hybrid population.
- Mitochondrial DNA
(mtDNA). The circular, maternally inherited genome carried by the mitochondrion, which is a cellular organelle.
- Genetic drift
The random fluctuation of allele frequencies in a population due to chance variations in the contribution of each individual to the next generation.
Describes a human pedigree that contains the descendants of common ancestors who lived several or many generations ago.
- Bayesian skyline plots
(BSPs). Plots of effective population size against time that summarize the demographic history of a population.
In the context of this Review, describes genetic variation that has no effect on selective fitness.
- Sertoli cell
Cells that are located in the walls of the seminiferous tubules of the testis and that act to support the development of sperm.
- Induced pluripotent stem cells
Stem cells that can be directly generated from adult cells and differentiated into many cell types.
- Genome-wide association studies
(GWAS). Studies of many common genome-wide variants (usually single-nucleotide polymorphisms) in different individuals that determine if any variant is associated with a particular trait.
Describes the behaviour of two regions of the sex chromosomes that display inheritance from both parents owing to crossing over between the X and Y chromosomes during male meiosis.
- Population stratification
Systematic differences in allele frequencies between subgroups within a population.
About this article
Cite this article
Jobling, M., Tyler-Smith, C. Human Y-chromosome variation in the genome-sequencing era. Nat Rev Genet 18, 485–497 (2017). https://doi.org/10.1038/nrg.2017.36
Comprehensive copy number analysis of Y chromosome-linked loci for detection of structural variations and diagnosis of male infertility
Journal of Human Genetics (2022)
Y-LineageTracker: a high-throughput analysis framework for Y-chromosomal next-generation sequencing data
BMC Bioinformatics (2021)
Human AZFb deletions cause distinct testicular pathologies depending on their extensions in Yq11 and the Y haplogroup: new cases and review of literature
Cell & Bioscience (2021)
Journal of Human Genetics (2021)
Structural and numerical Y chromosomal variations in elderly men identified through multiplex ligation-dependent probe amplification
Journal of Human Genetics (2021)