1 Lahn, B. T. & Page, D. C. Four evolutionary strata on the human X chromosome. Science 286, 964–967 (1999)

2 Bellott, D. W. et al. Convergent evolution of chicken Z and human X chromosomes by expansion and gene acquisition. Nature 466, 612–616 (2010)

3 Skaletsky, H. et al. The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature 423, 825–837 (2003)

4 Mueller, J. L. et al. Independent specialization of the human and mouse X chromosomes for the male germline. Nature Genet. 45, 1083–1087 (2013)

5 Hughes, J. F. et al. Strict evolutionary conservation followed rapid gene loss on human and rhesus Y chromosomes. Nature 483, 82–86 (2012)

6 Hughes, J. F. et al. Chimpanzee and human Y chromosomes are remarkably divergent in structure and gene content. Nature 463, 536–539 (2010)

7 Hughes, J. F. et al. Conservation of Y-linked genes during human evolution revealed by comparative sequencing in chimpanzee. Nature 437, 100–103 (2005)

8 Lahn, B. T. & Page, D. C. Functional coherence of the human Y chromosome. Science 278, 675–680 (1997)

9 Ross, M. T. et al. The DNA sequence of the human X chromosome. Nature 434, 325–337 (2005)

10 Watson, J. M., Spencer, J. A., Riggs, A. D. & Graves, J. A. The X chromosome of monotremes shares a highly conserved region with the eutherian and marsupial X chromosomes despite the absence of X chromosome inactivation. Proc. Natl Acad. Sci. USA 87, 7125–7129 (1990)

11 Murtagh, V. J. et al. Evolutionary history of novel genes on the tammar wallaby Y chromosome: implications for sex chromosome evolution. Genome Res. 22, 498–507 (2012)

12 Hedges, S. B., Dudley, J. & Kumar, S. TimeTree: a public knowledge-base of divergence times among organisms. Bioinformatics 22, 2971–2972 (2006)

13 Fisher, R. A. The evolution of dominance. Biol. Rev. Camb. Philos. Soc. 6, 345–368 (1931)

14 Rozen, S. et al. Abundant gene conversion between arms of palindromes in human and ape Y chromosomes. Nature 423, 873–876 (2003)

15 Kaiser, V. B., Zhou, Q. & Bachtrog, D. Nonrandom gene loss from the Drosophila miranda neo-Y chromosome. Genome Biol. Evol. 3, 1329–1337 (2011)

16 Jegalian, K. & Page, D. C. A proposed path by which genes common to mammalian X and Y chromosomes evolve to become X inactivated. Nature 394, 776–780 (1998)

17 Ohno, S. Sex Chromosomes and Sex-linked Genes (Springer-Verlag, 1967)

18 Huang, N., Lee, I., Marcotte, E. M. & Hurles, M. E. Characterising and predicting haploinsufficiency in the human genome. PLoS Genet. 6, e1001154 (2010)

19 Carrel, L. & Willard, H. F. X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature 434, 400–404 (2005)

20 Yang, F., Babak, T., Shendure, J. & Disteche, C. M. Global survey of escape from X inactivation by RNA-sequencing in mouse. Genome Res. 20, 614–622 (2010)

21 Merkin, J., Russell, C., Chen, P. & Burge, C. B. Evolutionary dynamics of gene and isoform regulation in mammalian tissues. Science 338, 1593–1599 (2012)

22 Xie, D. et al. Rewirable gene regulatory networks in the preimplantation embryonic development of three mammalian species. Genome Res. 20, 804–815 (2010)

23 Flicek, P. et al. Ensembl 2014. Nucleic Acids Res. 42, D749–D755 (2014)

24 Wang, X., Douglas, K. C., Vandeberg, J. L., Clark, A. G. & Samollow, P. B. Chromosome-wide profiling of X-chromosome inactivation and epigenetic states in fetal brain and placenta of the opossum, Monodelphis domestica. Genome Res. 24, 70–83 (2014)

25 Cockwell, A., MacKenzie, M., Youings, S. & Jacobs, P. A cytogenetic and molecular study of a series of 45,X fetuses and their parents. J. Med. Genet. 28, 151–155 (1991)

26 Hook, E. B. & Warburton, D. The distribution of chromosomal genotypes associated with Turner’s syndrome: livebirth prevalence rates and evidence for diminished fetal mortality and severity in genotypes associated with structural X abnormalities or mosaicism. Hum. Genet. 64, 24–27 (1983)

27 Hassold, T., Benham, F. & Leppert, M. Cytogenetic and molecular analysis of sex-chromosome monosomy. Am. J. Hum. Genet. 42, 534–541 (1988)

28 Burgoyne, P. S., Tam, P. P. & Evans, E. P. Retarded development of XO conceptuses during early pregnancy in the mouse. J. Reprod. Fertil. 68, 387–393 (1983)

29 Burgoyne, P. S. & Baker, T. G. Oocyte depletion in XO mice and their XX sibs from 12 to 200 days post partum. J. Reprod. Fertil. 61, 207–212 (1981)

30 Burgoyne, P. S., Evans, E. P. & Holland, K. XO monosomy is associated with reduced birthweight and lowered weight gain in the mouse. J. Reprod. Fertil. 68, 381–385 (1983)

31 Lindgren, A. M. et al. Haploinsufficiency of KDM6A is associated with severe psychomotor retardation, global growth restriction, seizures and cleft palate. Hum. Genet. 132, 537–552 (2013)

32 Rujirabanjerd, S. et al. Identification and characterization of two novel JARID1C mutations: suggestion of an emerging genotype-phenotype correlation. Eur. J. Hum. Genet. 18, 330–335 (2010)

33 Lawson-Yuen, A., Saldivar, J. S., Sommer, S. & Picker, J. Familial deletion within NLGN4 associated with autism and Tourette syndrome. Eur. J. Hum. Genet. 16, 614–618 (2008)

34 Huang, L. et al. A noncoding, regulatory mutation implicates HCFC1 in nonsyndromic intellectual disability. Am. J. Hum. Genet. 91, 694–702 (2012)

35 Ramocki, M. B., Tavyev, Y. J. & Peters, S. U. The MECP2 duplication syndrome. Am. J. Med. Genet. A. 152A, 1079–1088 (2010)

36 Froyen, G. et al. Copy-number gains of HUWE1 due to replication- and recombination-based rearrangements. Am. J. Hum. Genet. 91, 252–264 (2012)

37 Lau, E. C., Mohandas, T. K., Shapiro, L. J., Slavkin, H. C. & Snead, M. L. Human and mouse amelogenin gene loci are on the sex chromosomes. Genomics 4, 162–168 (1989)

38 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)

39 Watanabe, M., Zinn, A. R., Page, D. C. & Nishimoto, T. Functional equivalence of human X- and Y-encoded isoforms of ribosomal protein S4 consistent with a role in Turner syndrome. Nature Genet. 4, 268–271 (1993)

40 Sekiguchi, T., Iida, H., Fukumura, J. & Nishimoto, T. Human DDX3Y, the Y-encoded isoform of RNA helicase DDX3, rescues a hamster temperature-sensitive ET24 mutant cell line with a DDX3X mutation. Exp. Cell Res. 300, 213–222 (2004)

41 Welstead, G. G. et al. X-linked H3K27me3 demethylase Utx is required for embryonic development in a sex-specific manner. Proc. Natl Acad. Sci. USA 109, 13004–13009 (2012)

42 Shpargel, K. B., Sengoku, T., Yokoyama, S. & Magnuson, T. UTX and UTY demonstrate histone demethylase-independent function in mouse embryonic development. PLoS Genet. 8, e1002964 (2012)

43 Lee, S., Lee, J. W. & Lee, S. K. UTX, a histone H3-lysine 27 demethylase, acts as a critical switch to activate the cardiac developmental program. Dev. Cell 22, 25–37 (2012)

44 Slonim, D., Kruglyak, L., Stein, L. & Lander, E. Building human genome maps with radiation hybrids. J. Comput. Biol. 4, 487–504 (1997)

45 Saxena, R. et al. The DAZ gene cluster on the human Y chromosome arose from an autosomal gene that was transposed, repeatedly amplified and pruned. Nature Genet. 14, 292–299 (1996)

46 Yang, Z. PAML: a program package for phylogenetic analysis by maximum likelihood. Comput. Appl. Biosci. 13, 555–556 (1997)

47 Edgar, R. C. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 32, 1792–1797 (2004)

48 Felsenstein, J. PHYLIP - phylogeny inference package (version 3.2). Cladistics 5, 164–166 (1989)

49 Thomas, P. D. et al. PANTHER: a library of protein families and subfamilies indexed by function. Genome Res. 13, 2129–2141 (2003)

50 The UniProt Consortium Update on activities at the Universal Protein Resource (UniProt) in 2013. Nucleic Acids Res. 41, D43–D47 (2013)

51 Kuroda-Kawaguchi, T. et al. The AZFc region of the Y chromosome features massive palindromes and uniform recurrent deletions in infertile men. Nature Genet. 29, 279–286 (2001)

52 Karere, G. M., Froenicke, L., Millon, L., Womack, J. E. & Lyons, L. A. A high-resolution radiation hybrid map of rhesus macaque chromosome 5 identifies rearrangements in the genome assembly. Genomics 92, 210–218 (2008)

53 Mi, H., Muruganujan, A., Casagrande, J. T. & Thomas, P. D. Large-scale gene function analysis with the PANTHER classification system. Nature Protocols 8, 1551–1566 (2013)

54 Gubbay, J. et al. A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes. Nature 346, 245–250 (1990)

55 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)

56 Hayashida, H., Kuma, K. & Miyata, T. Interchromosomal gene conversion as a possible mechanism for explaining divergence patterns of ZFY-related genes. J. Mol. Evol. 35, 181–183 (1992)

57 Marais, G. & Galtier, N. Sex chromosomes: how X-Y recombination stops. Curr. Biol. 13, R641–R643 (2003)

58 Iwase, M. et al. The amelogenin loci span an ancient pseudoautosomal boundary in diverse mammalian species. Proc. Natl Acad. Sci. USA 100, 5258–5263 (2003)

59 Dal Zotto, L. et al. The mouse Mid1 gene: implications for the pathogenesis of Opitz syndrome and the evolution of the mammalian pseudoautosomal region. Hum. Mol. Genet. 7, 489–499 (1998)

60 Bachtrog, D. The temporal dynamics of processes underlying Y chromosome degeneration. Genetics 179, 1513–1525 (2008)

61 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)

62 Jones, M. H. et al. The Drosophila developmental gene fat facets has a human homologue in Xp11.4 which escapes X-inactivation and has related sequences on Yq11.2. Hum. Mol. Genet. 5, 1695–1701 (1996)

63 Adachi, M., Tachibana, K., Asakura, Y., Muroya, K. & Del Ogata, T. Del(X)(p21.1) in a mother and two daughters: genotype-phenotype correlation of Turner features. Hum. Genet. 106, 306–310 (2000)

64 Chocholska, S., Rossier, E., Barbi, G. & Kehrer-Sawatzki, H. Molecular cytogenetic analysis of a familial interstitial deletion Xp22.2-22.3 with a highly variable phenotype in female carriers. Am. J. Med. Genet. A. 140A, 604–610 (2006)

65 Good, C. D. et al. Dosage-sensitive X-linked locus influences the development of amygdala and orbitofrontal cortex, and fear recognition in humans. Brain 126, 2431–2446 (2003)

66 James, R. S. et al. A study of females with deletions of the short arm of the X chromosome. Hum. Genet. 102, 507–516 (1998)

67 Massa, G., Vanderschueren-Lodeweyckx, M. & Fryns, J. P. Deletion of the short arm of the X chromosome: a hereditary form of Turner syndrome. Eur. J. Pediatr. 151, 893–894 (1992)

68 Zinn, A. R. et al. Del (X)(p21.2) in a mother and two daughters with variable ovarian function. Clin. Genet. 52, 235–239 (1997)