Four evolutionary strata on the human X chromosome

Science

Volumn 286, Issue 5441, 1999, Pages 964-967

  Lahn, Bruce T ^a,b   Page, David C ^b  

^a UNIVERSITY OF CHICAGO   (United States)

^b HOWARD HUGHES MEDICAL INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; CHROMOSOMAL LOCALIZATION; CHROMOSOME MAP; EVOLUTION; GENE SEQUENCE; GENETIC RECOMBINATION; HUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; X CHROMOSOME; Y CHROMOSOME;

ANIMALS; CELL LINE; CHROMOSOME MAPPING; EVOLUTION, MOLECULAR; HUMANS; LINKAGE (GENETICS); RECOMBINATION, GENETIC; X CHROMOSOME; Y CHROMOSOME;

EID: 0033615708     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.286.5441.964     Document Type: Article

References (66)

1. J. J. Bull, Evolution of Sex Determining Mechanisms (Benjamin Cummings, Menlo Park, CA, 1983); J. A. Graves, Annu. Rev. Genet. 30, 233 (1996); B. Charlesworth, Curr. Biol. 6, 149 (1996); W. R. Rice, Bioscience 46, 331 (1995).
2. J. J. Bull, Evolution of Sex Determining Mechanisms (Benjamin Cummings, Menlo Park, CA, 1983); J. A. Graves, Annu. Rev. Genet. 30, 233 (1996); B. Charlesworth, Curr. Biol. 6, 149 (1996); W. R. Rice, Bioscience 46, 331 (1995).
3. J. J. Bull, Evolution of Sex Determining Mechanisms (Benjamin Cummings, Menlo Park, CA, 1983); J. A. Graves, Annu. Rev. Genet. 30, 233 (1996); B. Charlesworth, Curr. Biol. 6, 149 (1996); W. R. Rice, Bioscience 46, 331 (1995).
4. J. J. Bull, Evolution of Sex Determining Mechanisms (Benjamin Cummings, Menlo Park, CA, 1983); J. A. Graves, Annu. Rev. Genet. 30, 233 (1996); B. Charlesworth, Curr. Biol. 6, 149 (1996); W. R. Rice, Bioscience 46, 331 (1995).
5. The 19 X-Y gene pairs studied include the following: GYG2/GYG2P [J. Mu, A. V. Skurat, P. J. Roach, J. Biol. Chem. 272, 27589 (1997); (6)]. ARSD/AKSDP, ARSE/ ARSEP [ G. Meroni et al., Hum. Mol. Genet. 5, 423 (1996)], PRKX/Y [ A. Klink et al., Hum. Mol. Genet. 4, 869 (1995); K. Schiebel et al., Hum. Mol. Genet 6, 1985 (1997)], STS/STSP (76), KAL1/KALP [ B. Franco et al., Nature 353, 529 (1991); R. Legouis et al., Cell 67, 423 (1991); (17)], AMELX/Y [ Y. Nakahori, O. Takenaka, Y. Nakagome, Genomics 9, 264 (1991)], TB4X/Y [ H. Gondo et al., J. Immunol. 139, 3840 (1987); (5)], ZFX/Y [ D. C. Page et al., Cell 51, 1091 (1987); A. Schneider-Gädicke, P. Beer-Romero, L. C. Brown, R. Nussbaum, D. C. Page, Cell 57, 1247 (1989)], EIF1AX/Y [ T. E. Dever et al., J. Biol. Chem. 269, 3212 (1994); (5)], DFFRX/Y [ M. H. Jones et al., Hum. Mol. Genet 5, 1695 (1996); (5)], DBX/Y (5), CASK/CASKP [ A. R. Cohen et al., J. Cell Biol. 142, 129 (1998); (6)], UTX/Y (5), SMCX/Y [ J. Wu et al., Hum. Mol. Genet. 3, 153 (1994); A. I. Agulnik et al., Hum. Mol. Genet. 3, 879 (1994)], RPS4X/Y [ E. M. Fisher et al., Cell 63, 1205 (1990)], RBMX/Y [ M. Soulard et al., Nucleic Acids Res. 21, 4210 (1993); K. Ma et al., Cell 75, 1287 (1993); M. L. Delbridge, P. A. Lingenfelter, C. M. Disteche, J. A. Graves, Nature Genet. 22, 223 (1999); S. Mazeyrat N. Saut, M. G. Mattel, M. J. Mitchell, Nature Genet. 22, 224 (1999)], SOX3/SRY [ M. Stevanovic, R. Lovell-Badge, J. Collignon, P. N. Goodfellow, Hum. Mol. Genet. 2, 2013 (1993); A. H. Sinclair et al., Nature 346, 240 (1990)]. One interspecies pair was also studied: human UBE1X [ P. M. Handley, M. Mueckler, N. R. Siegel, A. Ciechanover, A. L. Schwartz, Proc. Natl. Acad. Sci. U.S.A. 88, 258 (1991)] and squirrel monkey UBF1Y (29). In humans, UBE1Y was deleted from the Y chromosome (29). We used squirrel monkey UBE1Y as a substitute.
6. The 19 X-Y gene pairs studied include the following: GYG2/GYG2P [J. Mu, A. V. Skurat, P. J. Roach, J. Biol. Chem. 272, 27589 (1997); (6)]. ARSD/AKSDP, ARSE/ ARSEP [ G. Meroni et al., Hum. Mol. Genet. 5, 423 (1996)], PRKX/Y [ A. Klink et al., Hum. Mol. Genet. 4, 869 (1995); K. Schiebel et al., Hum. Mol. Genet 6, 1985 (1997)], STS/STSP (76), KAL1/KALP [ B. Franco et al., Nature 353, 529 (1991); R. Legouis et al., Cell 67, 423 (1991); (17)], AMELX/Y [ Y. Nakahori, O. Takenaka, Y. Nakagome, Genomics 9, 264 (1991)], TB4X/Y [ H. Gondo et al., J. Immunol. 139, 3840 (1987); (5)], ZFX/Y [ D. C. Page et al., Cell 51, 1091 (1987); A. Schneider-Gädicke, P. Beer-Romero, L. C. Brown, R. Nussbaum, D. C. Page, Cell 57, 1247 (1989)], EIF1AX/Y [ T. E. Dever et al., J. Biol. Chem. 269, 3212 (1994); (5)], DFFRX/Y [ M. H. Jones et al., Hum. Mol. Genet 5, 1695 (1996); (5)], DBX/Y (5), CASK/CASKP [ A. R. Cohen et al., J. Cell Biol. 142, 129 (1998); (6)], UTX/Y (5), SMCX/Y [ J. Wu et al., Hum. Mol. Genet. 3, 153 (1994); A. I. Agulnik et al., Hum. Mol. Genet. 3, 879 (1994)], RPS4X/Y [ E. M. Fisher et al., Cell 63, 1205 (1990)], RBMX/Y [ M. Soulard et al., Nucleic Acids Res. 21, 4210 (1993); K. Ma et al., Cell 75, 1287 (1993); M. L. Delbridge, P. A. Lingenfelter, C. M. Disteche, J. A. Graves, Nature Genet. 22, 223 (1999); S. Mazeyrat N. Saut, M. G. Mattel, M. J. Mitchell, Nature Genet. 22, 224 (1999)], SOX3/SRY [ M. Stevanovic, R. Lovell-Badge, J. Collignon, P. N. Goodfellow, Hum. Mol. Genet. 2, 2013 (1993); A. H. Sinclair et al., Nature 346, 240 (1990)]. One interspecies pair was also studied: human UBE1X [ P. M. Handley, M. Mueckler, N. R. Siegel, A. Ciechanover, A. L. Schwartz, Proc. Natl. Acad. Sci. U.S.A. 88, 258 (1991)] and squirrel monkey UBF1Y (29). In humans, UBE1Y was deleted from the Y chromosome (29). We used squirrel monkey UBE1Y as a substitute.
7. The 19 X-Y gene pairs studied include the following: GYG2/GYG2P [J. Mu, A. V. Skurat, P. J. Roach, J. Biol. Chem. 272, 27589 (1997); (6)]. ARSD/AKSDP, ARSE/ ARSEP [ G. Meroni et al., Hum. Mol. Genet. 5, 423 (1996)], PRKX/Y [ A. Klink et al., Hum. Mol. Genet. 4, 869 (1995); K. Schiebel et al., Hum. Mol. Genet 6, 1985 (1997)], STS/STSP (76), KAL1/KALP [ B. Franco et al., Nature 353, 529 (1991); R. Legouis et al., Cell 67, 423 (1991); (17)], AMELX/Y [ Y. Nakahori, O. Takenaka, Y. Nakagome, Genomics 9, 264 (1991)], TB4X/Y [ H. Gondo et al., J. Immunol. 139, 3840 (1987); (5)], ZFX/Y [ D. C. Page et al., Cell 51, 1091 (1987); A. Schneider-Gädicke, P. Beer-Romero, L. C. Brown, R. Nussbaum, D. C. Page, Cell 57, 1247 (1989)], EIF1AX/Y [ T. E. Dever et al., J. Biol. Chem. 269, 3212 (1994); (5)], DFFRX/Y [ M. H. Jones et al., Hum. Mol. Genet 5, 1695 (1996); (5)], DBX/Y (5), CASK/CASKP [ A. R. Cohen et al., J. Cell Biol. 142, 129 (1998); (6)], UTX/Y (5), SMCX/Y [ J. Wu et al., Hum. Mol. Genet. 3, 153 (1994); A. I. Agulnik et al., Hum. Mol. Genet. 3, 879 (1994)], RPS4X/Y [ E. M. Fisher et al., Cell 63, 1205 (1990)], RBMX/Y [ M. Soulard et al., Nucleic Acids Res. 21, 4210 (1993); K. Ma et al., Cell 75, 1287 (1993); M. L. Delbridge, P. A. Lingenfelter, C. M. Disteche, J. A. Graves, Nature Genet. 22, 223 (1999); S. Mazeyrat N. Saut, M. G. Mattel, M. J. Mitchell, Nature Genet. 22, 224 (1999)], SOX3/SRY [ M. Stevanovic, R. Lovell-Badge, J. Collignon, P. N. Goodfellow, Hum. Mol. Genet. 2, 2013 (1993); A. H. Sinclair et al., Nature 346, 240 (1990)]. One interspecies pair was also studied: human UBE1X [ P. M. Handley, M. Mueckler, N. R. Siegel, A. Ciechanover, A. L. Schwartz, Proc. Natl. Acad. Sci. U.S.A. 88, 258 (1991)] and squirrel monkey UBF1Y (29). In humans, UBE1Y was deleted from the Y chromosome (29). We used squirrel monkey UBE1Y as a substitute.
8. The 19 X-Y gene pairs studied include the following: GYG2/GYG2P [J. Mu, A. V. Skurat, P. J. Roach, J. Biol. Chem. 272, 27589 (1997); (6)]. ARSD/AKSDP, ARSE/ ARSEP [ G. Meroni et al., Hum. Mol. Genet. 5, 423 (1996)], PRKX/Y [ A. Klink et al., Hum. Mol. Genet. 4, 869 (1995); K. Schiebel et al., Hum. Mol. Genet 6, 1985 (1997)], STS/STSP (76), KAL1/KALP [ B. Franco et al., Nature 353, 529 (1991); R. Legouis et al., Cell 67, 423 (1991); (17)], AMELX/Y [ Y. Nakahori, O. Takenaka, Y. Nakagome, Genomics 9, 264 (1991)], TB4X/Y [ H. Gondo et al., J. Immunol. 139, 3840 (1987); (5)], ZFX/Y [ D. C. Page et al., Cell 51, 1091 (1987); A. Schneider-Gädicke, P. Beer-Romero, L. C. Brown, R. Nussbaum, D. C. Page, Cell 57, 1247 (1989)], EIF1AX/Y [ T. E. Dever et al., J. Biol. Chem. 269, 3212 (1994); (5)], DFFRX/Y [ M. H. Jones et al., Hum. Mol. Genet 5, 1695 (1996); (5)], DBX/Y (5), CASK/CASKP [ A. R. Cohen et al., J. Cell Biol. 142, 129 (1998); (6)], UTX/Y (5), SMCX/Y [ J. Wu et al., Hum. Mol. Genet. 3, 153 (1994); A. I. Agulnik et al., Hum. Mol. Genet. 3, 879 (1994)], RPS4X/Y [ E. M. Fisher et al., Cell 63, 1205 (1990)], RBMX/Y [ M. Soulard et al., Nucleic Acids Res. 21, 4210 (1993); K. Ma et al., Cell 75, 1287 (1993); M. L. Delbridge, P. A. Lingenfelter, C. M. Disteche, J. A. Graves, Nature Genet. 22, 223 (1999); S. Mazeyrat N. Saut, M. G. Mattel, M. J. Mitchell, Nature Genet. 22, 224 (1999)], SOX3/SRY [ M. Stevanovic, R. Lovell-Badge, J. Collignon, P. N. Goodfellow, Hum. Mol. Genet. 2, 2013 (1993); A. H. Sinclair et al., Nature 346, 240 (1990)]. One interspecies pair was also studied: human UBE1X [ P. M. Handley, M. Mueckler, N. R. Siegel, A. Ciechanover, A. L. Schwartz, Proc. Natl. Acad. Sci. U.S.A. 88, 258 (1991)] and squirrel monkey UBF1Y (29). In humans, UBE1Y was deleted from the Y chromosome (29). We used squirrel monkey UBE1Y as a substitute.
9. The 19 X-Y gene pairs studied include the following: GYG2/GYG2P [J. Mu, A. V. Skurat, P. J. Roach, J. Biol. Chem. 272, 27589 (1997); (6)]. ARSD/AKSDP, ARSE/ ARSEP [ G. Meroni et al., Hum. Mol. Genet. 5, 423 (1996)], PRKX/Y [ A. Klink et al., Hum. Mol. Genet. 4, 869 (1995); K. Schiebel et al., Hum. Mol. Genet 6, 1985 (1997)], STS/STSP (76), KAL1/KALP [ B. Franco et al., Nature 353, 529 (1991); R. Legouis et al., Cell 67, 423 (1991); (17)], AMELX/Y [ Y. Nakahori, O. Takenaka, Y. Nakagome, Genomics 9, 264 (1991)], TB4X/Y [ H. Gondo et al., J. Immunol. 139, 3840 (1987); (5)], ZFX/Y [ D. C. Page et al., Cell 51, 1091 (1987); A. Schneider-Gädicke, P. Beer-Romero, L. C. Brown, R. Nussbaum, D. C. Page, Cell 57, 1247 (1989)], EIF1AX/Y [ T. E. Dever et al., J. Biol. Chem. 269, 3212 (1994); (5)], DFFRX/Y [ M. H. Jones et al., Hum. Mol. Genet 5, 1695 (1996); (5)], DBX/Y (5), CASK/CASKP [ A. R. Cohen et al., J. Cell Biol. 142, 129 (1998); (6)], UTX/Y (5), SMCX/Y [ J. Wu et al., Hum. Mol. Genet. 3, 153 (1994); A. I. Agulnik et al., Hum. Mol. Genet. 3, 879 (1994)], RPS4X/Y [ E. M. Fisher et al., Cell 63, 1205 (1990)], RBMX/Y [ M. Soulard et al., Nucleic Acids Res. 21, 4210 (1993); K. Ma et al., Cell 75, 1287 (1993); M. L. Delbridge, P. A. Lingenfelter, C. M. Disteche, J. A. Graves, Nature Genet. 22, 223 (1999); S. Mazeyrat N. Saut, M. G. Mattel, M. J. Mitchell, Nature Genet. 22, 224 (1999)], SOX3/SRY [ M. Stevanovic, R. Lovell-Badge, J. Collignon, P. N. Goodfellow, Hum. Mol. Genet. 2, 2013 (1993); A. H. Sinclair et al., Nature 346, 240 (1990)]. One interspecies pair was also studied: human UBE1X [ P. M. Handley, M. Mueckler, N. R. Siegel, A. Ciechanover, A. L. Schwartz, Proc. Natl. Acad. Sci. U.S.A. 88, 258 (1991)] and squirrel monkey UBF1Y (29). In humans, UBE1Y was deleted from the Y chromosome (29). We used squirrel monkey UBE1Y as a substitute.
10. The 19 X-Y gene pairs studied include the following: GYG2/GYG2P [J. Mu, A. V. Skurat, P. J. Roach, J. Biol. Chem. 272, 27589 (1997); (6)]. ARSD/AKSDP, ARSE/ ARSEP [ G. Meroni et al., Hum. Mol. Genet. 5, 423 (1996)], PRKX/Y [ A. Klink et al., Hum. Mol. Genet. 4, 869 (1995); K. Schiebel et al., Hum. Mol. Genet 6, 1985 (1997)], STS/STSP (76), KAL1/KALP [ B. Franco et al., Nature 353, 529 (1991); R. Legouis et al., Cell 67, 423 (1991); (17)], AMELX/Y [ Y. Nakahori, O. Takenaka, Y. Nakagome, Genomics 9, 264 (1991)], TB4X/Y [ H. Gondo et al., J. Immunol. 139, 3840 (1987); (5)], ZFX/Y [ D. C. Page et al., Cell 51, 1091 (1987); A. Schneider-Gädicke, P. Beer-Romero, L. C. Brown, R. Nussbaum, D. C. Page, Cell 57, 1247 (1989)], EIF1AX/Y [ T. E. Dever et al., J. Biol. Chem. 269, 3212 (1994); (5)], DFFRX/Y [ M. H. Jones et al., Hum. Mol. Genet 5, 1695 (1996); (5)], DBX/Y (5), CASK/CASKP [ A. R. Cohen et al., J. Cell Biol. 142, 129 (1998); (6)], UTX/Y (5), SMCX/Y [ J. Wu et al., Hum. Mol. Genet. 3, 153 (1994); A. I. Agulnik et al., Hum. Mol. Genet. 3, 879 (1994)], RPS4X/Y [ E. M. Fisher et al., Cell 63, 1205 (1990)], RBMX/Y [ M. Soulard et al., Nucleic Acids Res. 21, 4210 (1993); K. Ma et al., Cell 75, 1287 (1993); M. L. Delbridge, P. A. Lingenfelter, C. M. Disteche, J. A. Graves, Nature Genet. 22, 223 (1999); S. Mazeyrat N. Saut, M. G. Mattel, M. J. Mitchell, Nature Genet. 22, 224 (1999)], SOX3/SRY [ M. Stevanovic, R. Lovell-Badge, J. Collignon, P. N. Goodfellow, Hum. Mol. Genet. 2, 2013 (1993); A. H. Sinclair et al., Nature 346, 240 (1990)]. One interspecies pair was also studied: human UBE1X [ P. M. Handley, M. Mueckler, N. R. Siegel, A. Ciechanover, A. L. Schwartz, Proc. Natl. Acad. Sci. U.S.A. 88, 258 (1991)] and squirrel monkey UBF1Y (29). In humans, UBE1Y was deleted from the Y chromosome (29). We used squirrel monkey UBE1Y as a substitute.
11. The 19 X-Y gene pairs studied include the following: GYG2/GYG2P [J. Mu, A. V. Skurat, P. J. Roach, J. Biol. Chem. 272, 27589 (1997); (6)]. ARSD/AKSDP, ARSE/ ARSEP [ G. Meroni et al., Hum. Mol. Genet. 5, 423 (1996)], PRKX/Y [ A. Klink et al., Hum. Mol. Genet. 4, 869 (1995); K. Schiebel et al., Hum. Mol. Genet 6, 1985 (1997)], STS/STSP (76), KAL1/KALP [ B. Franco et al., Nature 353, 529 (1991); R. Legouis et al., Cell 67, 423 (1991); (17)], AMELX/Y [ Y. Nakahori, O. Takenaka, Y. Nakagome, Genomics 9, 264 (1991)], TB4X/Y [ H. Gondo et al., J. Immunol. 139, 3840 (1987); (5)], ZFX/Y [ D. C. Page et al., Cell 51, 1091 (1987); A. Schneider-Gädicke, P. Beer-Romero, L. C. Brown, R. Nussbaum, D. C. Page, Cell 57, 1247 (1989)], EIF1AX/Y [ T. E. Dever et al., J. Biol. Chem. 269, 3212 (1994); (5)], DFFRX/Y [ M. H. Jones et al., Hum. Mol. Genet 5, 1695 (1996); (5)], DBX/Y (5), CASK/CASKP [ A. R. Cohen et al., J. Cell Biol. 142, 129 (1998); (6)], UTX/Y (5), SMCX/Y [ J. Wu et al., Hum. Mol. Genet. 3, 153 (1994); A. I. Agulnik et al., Hum. Mol. Genet. 3, 879 (1994)], RPS4X/Y [ E. M. Fisher et al., Cell 63, 1205 (1990)], RBMX/Y [ M. Soulard et al., Nucleic Acids Res. 21, 4210 (1993); K. Ma et al., Cell 75, 1287 (1993); M. L. Delbridge, P. A. Lingenfelter, C. M. Disteche, J. A. Graves, Nature Genet. 22, 223 (1999); S. Mazeyrat N. Saut, M. G. Mattel, M. J. Mitchell, Nature Genet. 22, 224 (1999)], SOX3/SRY [ M. Stevanovic, R. Lovell-Badge, J. Collignon, P. N. Goodfellow, Hum. Mol. Genet. 2, 2013 (1993); A. H. Sinclair et al., Nature 346, 240 (1990)]. One interspecies pair was also studied: human UBE1X [ P. M. Handley, M. Mueckler, N. R. Siegel, A. Ciechanover, A. L. Schwartz, Proc. Natl. Acad. Sci. U.S.A. 88, 258 (1991)] and squirrel monkey UBF1Y (29). In humans, UBE1Y was deleted from the Y chromosome (29). We used squirrel monkey UBE1Y as a substitute.
12. The 19 X-Y gene pairs studied include the following: GYG2/GYG2P [J. Mu, A. V. Skurat, P. J. Roach, J. Biol. Chem. 272, 27589 (1997); (6)]. ARSD/AKSDP, ARSE/ ARSEP [ G. Meroni et al., Hum. Mol. Genet. 5, 423 (1996)], PRKX/Y [ A. Klink et al., Hum. Mol. Genet. 4, 869 (1995); K. Schiebel et al., Hum. Mol. Genet 6, 1985 (1997)], STS/STSP (76), KAL1/KALP [ B. Franco et al., Nature 353, 529 (1991); R. Legouis et al., Cell 67, 423 (1991); (17)], AMELX/Y [ Y. Nakahori, O. Takenaka, Y. Nakagome, Genomics 9, 264 (1991)], TB4X/Y [ H. Gondo et al., J. Immunol. 139, 3840 (1987); (5)], ZFX/Y [ D. C. Page et al., Cell 51, 1091 (1987); A. Schneider-Gädicke, P. Beer-Romero, L. C. Brown, R. Nussbaum, D. C. Page, Cell 57, 1247 (1989)], EIF1AX/Y [ T. E. Dever et al., J. Biol. Chem. 269, 3212 (1994); (5)], DFFRX/Y [ M. H. Jones et al., Hum. Mol. Genet 5, 1695 (1996); (5)], DBX/Y (5), CASK/CASKP [ A. R. Cohen et al., J. Cell Biol. 142, 129 (1998); (6)], UTX/Y (5), SMCX/Y [ J. Wu et al., Hum. Mol. Genet. 3, 153 (1994); A. I. Agulnik et al., Hum. Mol. Genet. 3, 879 (1994)], RPS4X/Y [ E. M. Fisher et al., Cell 63, 1205 (1990)], RBMX/Y [ M. Soulard et al., Nucleic Acids Res. 21, 4210 (1993); K. Ma et al., Cell 75, 1287 (1993); M. L. Delbridge, P. A. Lingenfelter, C. M. Disteche, J. A. Graves, Nature Genet. 22, 223 (1999); S. Mazeyrat N. Saut, M. G. Mattel, M. J. Mitchell, Nature Genet. 22, 224 (1999)], SOX3/SRY [ M. Stevanovic, R. Lovell-Badge, J. Collignon, P. N. Goodfellow, Hum. Mol. Genet. 2, 2013 (1993); A. H. Sinclair et al., Nature 346, 240 (1990)]. One interspecies pair was also studied: human UBE1X [ P. M. Handley, M. Mueckler, N. R. Siegel, A. Ciechanover, A. L. Schwartz, Proc. Natl. Acad. Sci. U.S.A. 88, 258 (1991)] and squirrel monkey UBF1Y (29). In humans, UBE1Y was deleted from the Y chromosome (29). We used squirrel monkey UBE1Y as a substitute.
13. The 19 X-Y gene pairs studied include the following: GYG2/GYG2P [J. Mu, A. V. Skurat, P. J. Roach, J. Biol. Chem. 272, 27589 (1997); (6)]. ARSD/AKSDP, ARSE/ ARSEP [ G. Meroni et al., Hum. Mol. Genet. 5, 423 (1996)], PRKX/Y [ A. Klink et al., Hum. Mol. Genet. 4, 869 (1995); K. Schiebel et al., Hum. Mol. Genet 6, 1985 (1997)], STS/STSP (76), KAL1/KALP [ B. Franco et al., Nature 353, 529 (1991); R. Legouis et al., Cell 67, 423 (1991); (17)], AMELX/Y [ Y. Nakahori, O. Takenaka, Y. Nakagome, Genomics 9, 264 (1991)], TB4X/Y [ H. Gondo et al., J. Immunol. 139, 3840 (1987); (5)], ZFX/Y [ D. C. Page et al., Cell 51, 1091 (1987); A. Schneider-Gädicke, P. Beer-Romero, L. C. Brown, R. Nussbaum, D. C. Page, Cell 57, 1247 (1989)], EIF1AX/Y [ T. E. Dever et al., J. Biol. Chem. 269, 3212 (1994); (5)], DFFRX/Y [ M. H. Jones et al., Hum. Mol. Genet 5, 1695 (1996); (5)], DBX/Y (5), CASK/CASKP [ A. R. Cohen et al., J. Cell Biol. 142, 129 (1998); (6)], UTX/Y (5), SMCX/Y [ J. Wu et al., Hum. Mol. Genet. 3, 153 (1994); A. I. Agulnik et al., Hum. Mol. Genet. 3, 879 (1994)], RPS4X/Y [ E. M. Fisher et al., Cell 63, 1205 (1990)], RBMX/Y [ M. Soulard et al., Nucleic Acids Res. 21, 4210 (1993); K. Ma et al., Cell 75, 1287 (1993); M. L. Delbridge, P. A. Lingenfelter, C. M. Disteche, J. A. Graves, Nature Genet. 22, 223 (1999); S. Mazeyrat N. Saut, M. G. Mattel, M. J. Mitchell, Nature Genet. 22, 224 (1999)], SOX3/SRY [ M. Stevanovic, R. Lovell-Badge, J. Collignon, P. N. Goodfellow, Hum. Mol. Genet. 2, 2013 (1993); A. H. Sinclair et al., Nature 346, 240 (1990)]. One interspecies pair was also studied: human UBE1X [ P. M. Handley, M. Mueckler, N. R. Siegel, A. Ciechanover, A. L. Schwartz, Proc. Natl. Acad. Sci. U.S.A. 88, 258 (1991)] and squirrel monkey UBF1Y (29). In humans, UBE1Y was deleted from the Y chromosome (29). We used squirrel monkey UBE1Y as a substitute.
14. The 19 X-Y gene pairs studied include the following: GYG2/GYG2P [J. Mu, A. V. Skurat, P. J. Roach, J. Biol. Chem. 272, 27589 (1997); (6)]. ARSD/AKSDP, ARSE/ ARSEP [ G. Meroni et al., Hum. Mol. Genet. 5, 423 (1996)], PRKX/Y [ A. Klink et al., Hum. Mol. Genet. 4, 869 (1995); K. Schiebel et al., Hum. Mol. Genet 6, 1985 (1997)], STS/STSP (76), KAL1/KALP [ B. Franco et al., Nature 353, 529 (1991); R. Legouis et al., Cell 67, 423 (1991); (17)], AMELX/Y [ Y. Nakahori, O. Takenaka, Y. Nakagome, Genomics 9, 264 (1991)], TB4X/Y [ H. Gondo et al., J. Immunol. 139, 3840 (1987); (5)], ZFX/Y [ D. C. Page et al., Cell 51, 1091 (1987); A. Schneider-Gädicke, P. Beer-Romero, L. C. Brown, R. Nussbaum, D. C. Page, Cell 57, 1247 (1989)], EIF1AX/Y [ T. E. Dever et al., J. Biol. Chem. 269, 3212 (1994); (5)], DFFRX/Y [ M. H. Jones et al., Hum. Mol. Genet 5, 1695 (1996); (5)], DBX/Y (5), CASK/CASKP [ A. R. Cohen et al., J. Cell Biol. 142, 129 (1998); (6)], UTX/Y (5), SMCX/Y [ J. Wu et al., Hum. Mol. Genet. 3, 153 (1994); A. I. Agulnik et al., Hum. Mol. Genet. 3, 879 (1994)], RPS4X/Y [ E. M. Fisher et al., Cell 63, 1205 (1990)], RBMX/Y [ M. Soulard et al., Nucleic Acids Res. 21, 4210 (1993); K. Ma et al., Cell 75, 1287 (1993); M. L. Delbridge, P. A. Lingenfelter, C. M. Disteche, J. A. Graves, Nature Genet. 22, 223 (1999); S. Mazeyrat N. Saut, M. G. Mattel, M. J. Mitchell, Nature Genet. 22, 224 (1999)], SOX3/SRY [ M. Stevanovic, R. Lovell-Badge, J. Collignon, P. N. Goodfellow, Hum. Mol. Genet. 2, 2013 (1993); A. H. Sinclair et al., Nature 346, 240 (1990)]. One interspecies pair was also studied: human UBE1X [ P. M. Handley, M. Mueckler, N. R. Siegel, A. Ciechanover, A. L. Schwartz, Proc. Natl. Acad. Sci. U.S.A. 88, 258 (1991)] and squirrel monkey UBF1Y (29). In humans, UBE1Y was deleted from the Y chromosome (29). We used squirrel monkey UBE1Y as a substitute.
15. The 19 X-Y gene pairs studied include the following: GYG2/GYG2P [J. Mu, A. V. Skurat, P. J. Roach, J. Biol. Chem. 272, 27589 (1997); (6)]. ARSD/AKSDP, ARSE/ ARSEP [ G. Meroni et al., Hum. Mol. Genet. 5, 423 (1996)], PRKX/Y [ A. Klink et al., Hum. Mol. Genet. 4, 869 (1995); K. Schiebel et al., Hum. Mol. Genet 6, 1985 (1997)], STS/STSP (76), KAL1/KALP [ B. Franco et al., Nature 353, 529 (1991); R. Legouis et al., Cell 67, 423 (1991); (17)], AMELX/Y [ Y. Nakahori, O. Takenaka, Y. Nakagome, Genomics 9, 264 (1991)], TB4X/Y [ H. Gondo et al., J. Immunol. 139, 3840 (1987); (5)], ZFX/Y [ D. C. Page et al., Cell 51, 1091 (1987); A. Schneider-Gädicke, P. Beer-Romero, L. C. Brown, R. Nussbaum, D. C. Page, Cell 57, 1247 (1989)], EIF1AX/Y [ T. E. Dever et al., J. Biol. Chem. 269, 3212 (1994); (5)], DFFRX/Y [ M. H. Jones et al., Hum. Mol. Genet 5, 1695 (1996); (5)], DBX/Y (5), CASK/CASKP [ A. R. Cohen et al., J. Cell Biol. 142, 129 (1998); (6)], UTX/Y (5), SMCX/Y [ J. Wu et al., Hum. Mol. Genet. 3, 153 (1994); A. I. Agulnik et al., Hum. Mol. Genet. 3, 879 (1994)], RPS4X/Y [ E. M. Fisher et al., Cell 63, 1205 (1990)], RBMX/Y [ M. Soulard et al., Nucleic Acids Res. 21, 4210 (1993); K. Ma et al., Cell 75, 1287 (1993); M. L. Delbridge, P. A. Lingenfelter, C. M. Disteche, J. A. Graves, Nature Genet. 22, 223 (1999); S. Mazeyrat N. Saut, M. G. Mattel, M. J. Mitchell, Nature Genet. 22, 224 (1999)], SOX3/SRY [ M. Stevanovic, R. Lovell-Badge, J. Collignon, P. N. Goodfellow, Hum. Mol. Genet. 2, 2013 (1993); A. H. Sinclair et al., Nature 346, 240 (1990)]. One interspecies pair was also studied: human UBE1X [ P. M. Handley, M. Mueckler, N. R. Siegel, A. Ciechanover, A. L. Schwartz, Proc. Natl. Acad. Sci. U.S.A. 88, 258 (1991)] and squirrel monkey UBF1Y (29). In humans, UBE1Y was deleted from the Y chromosome (29). We used squirrel monkey UBE1Y as a substitute.
16. The 19 X-Y gene pairs studied include the following: GYG2/GYG2P [J. Mu, A. V. Skurat, P. J. Roach, J. Biol. Chem. 272, 27589 (1997); (6)]. ARSD/AKSDP, ARSE/ ARSEP [ G. Meroni et al., Hum. Mol. Genet. 5, 423 (1996)], PRKX/Y [ A. Klink et al., Hum. Mol. Genet. 4, 869 (1995); K. Schiebel et al., Hum. Mol. Genet 6, 1985 (1997)], STS/STSP (76), KAL1/KALP [ B. Franco et al., Nature 353, 529 (1991); R. Legouis et al., Cell 67, 423 (1991); (17)], AMELX/Y [ Y. Nakahori, O. Takenaka, Y. Nakagome, Genomics 9, 264 (1991)], TB4X/Y [ H. Gondo et al., J. Immunol. 139, 3840 (1987); (5)], ZFX/Y [ D. C. Page et al., Cell 51, 1091 (1987); A. Schneider-Gädicke, P. Beer-Romero, L. C. Brown, R. Nussbaum, D. C. Page, Cell 57, 1247 (1989)], EIF1AX/Y [ T. E. Dever et al., J. Biol. Chem. 269, 3212 (1994); (5)], DFFRX/Y [ M. H. Jones et al., Hum. Mol. Genet 5, 1695 (1996); (5)], DBX/Y (5), CASK/CASKP [ A. R. Cohen et al., J. Cell Biol. 142, 129 (1998); (6)], UTX/Y (5), SMCX/Y [ J. Wu et al., Hum. Mol. Genet. 3, 153 (1994); A. I. Agulnik et al., Hum. Mol. Genet. 3, 879 (1994)], RPS4X/Y [ E. M. Fisher et al., Cell 63, 1205 (1990)], RBMX/Y [ M. Soulard et al., Nucleic Acids Res. 21, 4210 (1993); K. Ma et al., Cell 75, 1287 (1993); M. L. Delbridge, P. A. Lingenfelter, C. M. Disteche, J. A. Graves, Nature Genet. 22, 223 (1999); S. Mazeyrat N. Saut, M. G. Mattel, M. J. Mitchell, Nature Genet. 22, 224 (1999)], SOX3/SRY [ M. Stevanovic, R. Lovell-Badge, J. Collignon, P. N. Goodfellow, Hum. Mol. Genet. 2, 2013 (1993); A. H. Sinclair et al., Nature 346, 240 (1990)]. One interspecies pair was also studied: human UBE1X [ P. M. Handley, M. Mueckler, N. R. Siegel, A. Ciechanover, A. L. Schwartz, Proc. Natl. Acad. Sci. U.S.A. 88, 258 (1991)] and squirrel monkey UBF1Y (29). In humans, UBE1Y was deleted from the Y chromosome (29). We used squirrel monkey UBE1Y as a substitute.
17. The 19 X-Y gene pairs studied include the following: GYG2/GYG2P [J. Mu, A. V. Skurat, P. J. Roach, J. Biol. Chem. 272, 27589 (1997); (6)]. ARSD/AKSDP, ARSE/ ARSEP [ G. Meroni et al., Hum. Mol. Genet. 5, 423 (1996)], PRKX/Y [ A. Klink et al., Hum. Mol. Genet. 4, 869 (1995); K. Schiebel et al., Hum. Mol. Genet 6, 1985 (1997)], STS/STSP (76), KAL1/KALP [ B. Franco et al., Nature 353, 529 (1991); R. Legouis et al., Cell 67, 423 (1991); (17)], AMELX/Y [ Y. Nakahori, O. Takenaka, Y. Nakagome, Genomics 9, 264 (1991)], TB4X/Y [ H. Gondo et al., J. Immunol. 139, 3840 (1987); (5)], ZFX/Y [ D. C. Page et al., Cell 51, 1091 (1987); A. Schneider-Gädicke, P. Beer-Romero, L. C. Brown, R. Nussbaum, D. C. Page, Cell 57, 1247 (1989)], EIF1AX/Y [ T. E. Dever et al., J. Biol. Chem. 269, 3212 (1994); (5)], DFFRX/Y [ M. H. Jones et al., Hum. Mol. Genet 5, 1695 (1996); (5)], DBX/Y (5), CASK/CASKP [ A. R. Cohen et al., J. Cell Biol. 142, 129 (1998); (6)], UTX/Y (5), SMCX/Y [ J. Wu et al., Hum. Mol. Genet. 3, 153 (1994); A. I. Agulnik et al., Hum. Mol. Genet. 3, 879 (1994)], RPS4X/Y [ E. M. Fisher et al., Cell 63, 1205 (1990)], RBMX/Y [ M. Soulard et al., Nucleic Acids Res. 21, 4210 (1993); K. Ma et al., Cell 75, 1287 (1993); M. L. Delbridge, P. A. Lingenfelter, C. M. Disteche, J. A. Graves, Nature Genet. 22, 223 (1999); S. Mazeyrat N. Saut, M. G. Mattel, M. J. Mitchell, Nature Genet. 22, 224 (1999)], SOX3/SRY [ M. Stevanovic, R. Lovell-Badge, J. Collignon, P. N. Goodfellow, Hum. Mol. Genet. 2, 2013 (1993); A. H. Sinclair et al., Nature 346, 240 (1990)]. One interspecies pair was also studied: human UBE1X [ P. M. Handley, M. Mueckler, N. R. Siegel, A. Ciechanover, A. L. Schwartz, Proc. Natl. Acad. Sci. U.S.A. 88, 258 (1991)] and squirrel monkey UBF1Y (29). In humans, UBE1Y was deleted from the Y chromosome (29). We used squirrel monkey UBE1Y as a substitute.
18. The 19 X-Y gene pairs studied include the following: GYG2/GYG2P [J. Mu, A. V. Skurat, P. J. Roach, J. Biol. Chem. 272, 27589 (1997); (6)]. ARSD/AKSDP, ARSE/ ARSEP [ G. Meroni et al., Hum. Mol. Genet. 5, 423 (1996)], PRKX/Y [ A. Klink et al., Hum. Mol. Genet. 4, 869 (1995); K. Schiebel et al., Hum. Mol. Genet 6, 1985 (1997)], STS/STSP (76), KAL1/KALP [ B. Franco et al., Nature 353, 529 (1991); R. Legouis et al., Cell 67, 423 (1991); (17)], AMELX/Y [ Y. Nakahori, O. Takenaka, Y. Nakagome, Genomics 9, 264 (1991)], TB4X/Y [ H. Gondo et al., J. Immunol. 139, 3840 (1987); (5)], ZFX/Y [ D. C. Page et al., Cell 51, 1091 (1987); A. Schneider-Gädicke, P. Beer-Romero, L. C. Brown, R. Nussbaum, D. C. Page, Cell 57, 1247 (1989)], EIF1AX/Y [ T. E. Dever et al., J. Biol. Chem. 269, 3212 (1994); (5)], DFFRX/Y [ M. H. Jones et al., Hum. Mol. Genet 5, 1695 (1996); (5)], DBX/Y (5), CASK/CASKP [ A. R. Cohen et al., J. Cell Biol. 142, 129 (1998); (6)], UTX/Y (5), SMCX/Y [ J. Wu et al., Hum. Mol. Genet. 3, 153 (1994); A. I. Agulnik et al., Hum. Mol. Genet. 3, 879 (1994)], RPS4X/Y [ E. M. Fisher et al., Cell 63, 1205 (1990)], RBMX/Y [ M. Soulard et al., Nucleic Acids Res. 21, 4210 (1993); K. Ma et al., Cell 75, 1287 (1993); M. L. Delbridge, P. A. Lingenfelter, C. M. Disteche, J. A. Graves, Nature Genet. 22, 223 (1999); S. Mazeyrat N. Saut, M. G. Mattel, M. J. Mitchell, Nature Genet. 22, 224 (1999)], SOX3/SRY [ M. Stevanovic, R. Lovell-Badge, J. Collignon, P. N. Goodfellow, Hum. Mol. Genet. 2, 2013 (1993); A. H. Sinclair et al., Nature 346, 240 (1990)]. One interspecies pair was also studied: human UBE1X [ P. M. Handley, M. Mueckler, N. R. Siegel, A. Ciechanover, A. L. Schwartz, Proc. Natl. Acad. Sci. U.S.A. 88, 258 (1991)] and squirrel monkey UBF1Y (29). In humans, UBE1Y was deleted from the Y chromosome (29). We used squirrel monkey UBE1Y as a substitute.
19. The 19 X-Y gene pairs studied include the following: GYG2/GYG2P [J. Mu, A. V. Skurat, P. J. Roach, J. Biol. Chem. 272, 27589 (1997); (6)]. ARSD/AKSDP, ARSE/ ARSEP [ G. Meroni et al., Hum. Mol. Genet. 5, 423 (1996)], PRKX/Y [ A. Klink et al., Hum. Mol. Genet. 4, 869 (1995); K. Schiebel et al., Hum. Mol. Genet 6, 1985 (1997)], STS/STSP (76), KAL1/KALP [ B. Franco et al., Nature 353, 529 (1991); R. Legouis et al., Cell 67, 423 (1991); (17)], AMELX/Y [ Y. Nakahori, O. Takenaka, Y. Nakagome, Genomics 9, 264 (1991)], TB4X/Y [ H. Gondo et al., J. Immunol. 139, 3840 (1987); (5)], ZFX/Y [ D. C. Page et al., Cell 51, 1091 (1987); A. Schneider-Gädicke, P. Beer-Romero, L. C. Brown, R. Nussbaum, D. C. Page, Cell 57, 1247 (1989)], EIF1AX/Y [ T. E. Dever et al., J. Biol. Chem. 269, 3212 (1994); (5)], DFFRX/Y [ M. H. Jones et al., Hum. Mol. Genet 5, 1695 (1996); (5)], DBX/Y (5), CASK/CASKP [ A. R. Cohen et al., J. Cell Biol. 142, 129 (1998); (6)], UTX/Y (5), SMCX/Y [ J. Wu et al., Hum. Mol. Genet. 3, 153 (1994); A. I. Agulnik et al., Hum. Mol. Genet. 3, 879 (1994)], RPS4X/Y [ E. M. Fisher et al., Cell 63, 1205 (1990)], RBMX/Y [ M. Soulard et al., Nucleic Acids Res. 21, 4210 (1993); K. Ma et al., Cell 75, 1287 (1993); M. L. Delbridge, P. A. Lingenfelter, C. M. Disteche, J. A. Graves, Nature Genet. 22, 223 (1999); S. Mazeyrat N. Saut, M. G. Mattel, M. J. Mitchell, Nature Genet. 22, 224 (1999)], SOX3/SRY [ M. Stevanovic, R. Lovell-Badge, J. Collignon, P. N. Goodfellow, Hum. Mol. Genet. 2, 2013 (1993); A. H. Sinclair et al., Nature 346, 240 (1990)]. One interspecies pair was also studied: human UBE1X [ P. M. Handley, M. Mueckler, N. R. Siegel, A. Ciechanover, A. L. Schwartz, Proc. Natl. Acad. Sci. U.S.A. 88, 258 (1991)] and squirrel monkey UBF1Y (29). In humans, UBE1Y was deleted from the Y chromosome (29). We used squirrel monkey UBE1Y as a substitute.
20. The 19 X-Y gene pairs studied include the following: GYG2/GYG2P [J. Mu, A. V. Skurat, P. J. Roach, J. Biol. Chem. 272, 27589 (1997); (6)]. ARSD/AKSDP, ARSE/ ARSEP [ G. Meroni et al., Hum. Mol. Genet. 5, 423 (1996)], PRKX/Y [ A. Klink et al., Hum. Mol. Genet. 4, 869 (1995); K. Schiebel et al., Hum. Mol. Genet 6, 1985 (1997)], STS/STSP (76), KAL1/KALP [ B. Franco et al., Nature 353, 529 (1991); R. Legouis et al., Cell 67, 423 (1991); (17)], AMELX/Y [ Y. Nakahori, O. Takenaka, Y. Nakagome, Genomics 9, 264 (1991)], TB4X/Y [ H. Gondo et al., J. Immunol. 139, 3840 (1987); (5)], ZFX/Y [ D. C. Page et al., Cell 51, 1091 (1987); A. Schneider-Gädicke, P. Beer-Romero, L. C. Brown, R. Nussbaum, D. C. Page, Cell 57, 1247 (1989)], EIF1AX/Y [ T. E. Dever et al., J. Biol. Chem. 269, 3212 (1994); (5)], DFFRX/Y [ M. H. Jones et al., Hum. Mol. Genet 5, 1695 (1996); (5)], DBX/Y (5), CASK/CASKP [ A. R. Cohen et al., J. Cell Biol. 142, 129 (1998); (6)], UTX/Y (5), SMCX/Y [ J. Wu et al., Hum. Mol. Genet. 3, 153 (1994); A. I. Agulnik et al., Hum. Mol. Genet. 3, 879 (1994)], RPS4X/Y [ E. M. Fisher et al., Cell 63, 1205 (1990)], RBMX/Y [ M. Soulard et al., Nucleic Acids Res. 21, 4210 (1993); K. Ma et al., Cell 75, 1287 (1993); M. L. Delbridge, P. A. Lingenfelter, C. M. Disteche, J. A. Graves, Nature Genet. 22, 223 (1999); S. Mazeyrat N. Saut, M. G. Mattel, M. J. Mitchell, Nature Genet. 22, 224 (1999)], SOX3/SRY [ M. Stevanovic, R. Lovell-Badge, J. Collignon, P. N. Goodfellow, Hum. Mol. Genet. 2, 2013 (1993); A. H. Sinclair et al., Nature 346, 240 (1990)]. One interspecies pair was also studied: human UBE1X [ P. M. Handley, M. Mueckler, N. R. Siegel, A. Ciechanover, A. L. Schwartz, Proc. Natl. Acad. Sci. U.S.A. 88, 258 (1991)] and squirrel monkey UBF1Y (29). In humans, UBE1Y was deleted from the Y chromosome (29). We used squirrel monkey UBE1Y as a substitute.
21. The 19 X-Y gene pairs studied include the following: GYG2/GYG2P [J. Mu, A. V. Skurat, P. J. Roach, J. Biol. Chem. 272, 27589 (1997); (6)]. ARSD/AKSDP, ARSE/ ARSEP [ G. Meroni et al., Hum. Mol. Genet. 5, 423 (1996)], PRKX/Y [ A. Klink et al., Hum. Mol. Genet. 4, 869 (1995); K. Schiebel et al., Hum. Mol. Genet 6, 1985 (1997)], STS/STSP (76), KAL1/KALP [ B. Franco et al., Nature 353, 529 (1991); R. Legouis et al., Cell 67, 423 (1991); (17)], AMELX/Y [ Y. Nakahori, O. Takenaka, Y. Nakagome, Genomics 9, 264 (1991)], TB4X/Y [ H. Gondo et al., J. Immunol. 139, 3840 (1987); (5)], ZFX/Y [ D. C. Page et al., Cell 51, 1091 (1987); A. Schneider-Gädicke, P. Beer-Romero, L. C. Brown, R. Nussbaum, D. C. Page, Cell 57, 1247 (1989)], EIF1AX/Y [ T. E. Dever et al., J. Biol. Chem. 269, 3212 (1994); (5)], DFFRX/Y [ M. H. Jones et al., Hum. Mol. Genet 5, 1695 (1996); (5)], DBX/Y (5), CASK/CASKP [ A. R. Cohen et al., J. Cell Biol. 142, 129 (1998); (6)], UTX/Y (5), SMCX/Y [ J. Wu et al., Hum. Mol. Genet. 3, 153 (1994); A. I. Agulnik et al., Hum. Mol. Genet. 3, 879 (1994)], RPS4X/Y [ E. M. Fisher et al., Cell 63, 1205 (1990)], RBMX/Y [ M. Soulard et al., Nucleic Acids Res. 21, 4210 (1993); K. Ma et al., Cell 75, 1287 (1993); M. L. Delbridge, P. A. Lingenfelter, C. M. Disteche, J. A. Graves, Nature Genet. 22, 223 (1999); S. Mazeyrat N. Saut, M. G. Mattel, M. J. Mitchell, Nature Genet. 22, 224 (1999)], SOX3/SRY [ M. Stevanovic, R. Lovell-Badge, J. Collignon, P. N. Goodfellow, Hum. Mol. Genet. 2, 2013 (1993); A. H. Sinclair et al., Nature 346, 240 (1990)]. One interspecies pair was also studied: human UBE1X [ P. M. Handley, M. Mueckler, N. R. Siegel, A. Ciechanover, A. L. Schwartz, Proc. Natl. Acad. Sci. U.S.A. 88, 258 (1991)] and squirrel monkey UBF1Y (29). In humans, UBE1Y was deleted from the Y chromosome (29). We used squirrel monkey UBE1Y as a substitute.
22. The 19 X-Y gene pairs studied include the following: GYG2/GYG2P [J. Mu, A. V. Skurat, P. J. Roach, J. Biol. Chem. 272, 27589 (1997); (6)]. ARSD/AKSDP, ARSE/ ARSEP [ G. Meroni et al., Hum. Mol. Genet. 5, 423 (1996)], PRKX/Y [ A. Klink et al., Hum. Mol. Genet. 4, 869 (1995); K. Schiebel et al., Hum. Mol. Genet 6, 1985 (1997)], STS/STSP (76), KAL1/KALP [ B. Franco et al., Nature 353, 529 (1991); R. Legouis et al., Cell 67, 423 (1991); (17)], AMELX/Y [ Y. Nakahori, O. Takenaka, Y. Nakagome, Genomics 9, 264 (1991)], TB4X/Y [ H. Gondo et al., J. Immunol. 139, 3840 (1987); (5)], ZFX/Y [ D. C. Page et al., Cell 51, 1091 (1987); A. Schneider-Gädicke, P. Beer-Romero, L. C. Brown, R. Nussbaum, D. C. Page, Cell 57, 1247 (1989)], EIF1AX/Y [ T. E. Dever et al., J. Biol. Chem. 269, 3212 (1994); (5)], DFFRX/Y [ M. H. Jones et al., Hum. Mol. Genet 5, 1695 (1996); (5)], DBX/Y (5), CASK/CASKP [ A. R. Cohen et al., J. Cell Biol. 142, 129 (1998); (6)], UTX/Y (5), SMCX/Y [ J. Wu et al., Hum. Mol. Genet. 3, 153 (1994); A. I. Agulnik et al., Hum. Mol. Genet. 3, 879 (1994)], RPS4X/Y [ E. M. Fisher et al., Cell 63, 1205 (1990)], RBMX/Y [ M. Soulard et al., Nucleic Acids Res. 21, 4210 (1993); K. Ma et al., Cell 75, 1287 (1993); M. L. Delbridge, P. A. Lingenfelter, C. M. Disteche, J. A. Graves, Nature Genet. 22, 223 (1999); S. Mazeyrat N. Saut, M. G. Mattel, M. J. Mitchell, Nature Genet. 22, 224 (1999)], SOX3/SRY [ M. Stevanovic, R. Lovell-Badge, J. Collignon, P. N. Goodfellow, Hum. Mol. Genet. 2, 2013 (1993); A. H. Sinclair et al., Nature 346, 240 (1990)]. One interspecies pair was also studied: human UBE1X [ P. M. Handley, M. Mueckler, N. R. Siegel, A. Ciechanover, A. L. Schwartz, Proc. Natl. Acad. Sci. U.S.A. 88, 258 (1991)] and squirrel monkey UBF1Y (29). In humans, UBE1Y was deleted from the Y chromosome (29). We used squirrel monkey UBE1Y as a substitute.
23. The 19 X-Y gene pairs studied include the following: GYG2/GYG2P [J. Mu, A. V. Skurat, P. J. Roach, J. Biol. Chem. 272, 27589 (1997); (6)]. ARSD/AKSDP, ARSE/ ARSEP [ G. Meroni et al., Hum. Mol. Genet. 5, 423 (1996)], PRKX/Y [ A. Klink et al., Hum. Mol. Genet. 4, 869 (1995); K. Schiebel et al., Hum. Mol. Genet 6, 1985 (1997)], STS/STSP (76), KAL1/KALP [ B. Franco et al., Nature 353, 529 (1991); R. Legouis et al., Cell 67, 423 (1991); (17)], AMELX/Y [ Y. Nakahori, O. Takenaka, Y. Nakagome, Genomics 9, 264 (1991)], TB4X/Y [ H. Gondo et al., J. Immunol. 139, 3840 (1987); (5)], ZFX/Y [ D. C. Page et al., Cell 51, 1091 (1987); A. Schneider-Gädicke, P. Beer-Romero, L. C. Brown, R. Nussbaum, D. C. Page, Cell 57, 1247 (1989)], EIF1AX/Y [ T. E. Dever et al., J. Biol. Chem. 269, 3212 (1994); (5)], DFFRX/Y [ M. H. Jones et al., Hum. Mol. Genet 5, 1695 (1996); (5)], DBX/Y (5), CASK/CASKP [ A. R. Cohen et al., J. Cell Biol. 142, 129 (1998); (6)], UTX/Y (5), SMCX/Y [ J. Wu et al., Hum. Mol. Genet. 3, 153 (1994); A. I. Agulnik et al., Hum. Mol. Genet. 3, 879 (1994)], RPS4X/Y [ E. M. Fisher et al., Cell 63, 1205 (1990)], RBMX/Y [ M. Soulard et al., Nucleic Acids Res. 21, 4210 (1993); K. Ma et al., Cell 75, 1287 (1993); M. L. Delbridge, P. A. Lingenfelter, C. M. Disteche, J. A. Graves, Nature Genet. 22, 223 (1999); S. Mazeyrat N. Saut, M. G. Mattel, M. J. Mitchell, Nature Genet. 22, 224 (1999)], SOX3/SRY [ M. Stevanovic, R. Lovell-Badge, J. Collignon, P. N. Goodfellow, Hum. Mol. Genet. 2, 2013 (1993); A. H. Sinclair et al., Nature 346, 240 (1990)]. One interspecies pair was also studied: human UBE1X [ P. M. Handley, M. Mueckler, N. R. Siegel, A. Ciechanover, A. L. Schwartz, Proc. Natl. Acad. Sci. U.S.A. 88, 258 (1991)] and squirrel monkey UBF1Y (29). In humans, UBE1Y was deleted from the Y chromosome (29). We used squirrel monkey UBE1Y as a substitute.
24. The 19 X-Y gene pairs studied include the following: GYG2/GYG2P [J. Mu, A. V. Skurat, P. J. Roach, J. Biol. Chem. 272, 27589 (1997); (6)]. ARSD/AKSDP, ARSE/ ARSEP [ G. Meroni et al., Hum. Mol. Genet. 5, 423 (1996)], PRKX/Y [ A. Klink et al., Hum. Mol. Genet. 4, 869 (1995); K. Schiebel et al., Hum. Mol. Genet 6, 1985 (1997)], STS/STSP (76), KAL1/KALP [ B. Franco et al., Nature 353, 529 (1991); R. Legouis et al., Cell 67, 423 (1991); (17)], AMELX/Y [ Y. Nakahori, O. Takenaka, Y. Nakagome, Genomics 9, 264 (1991)], TB4X/Y [ H. Gondo et al., J. Immunol. 139, 3840 (1987); (5)], ZFX/Y [ D. C. Page et al., Cell 51, 1091 (1987); A. Schneider-Gädicke, P. Beer-Romero, L. C. Brown, R. Nussbaum, D. C. Page, Cell 57, 1247 (1989)], EIF1AX/Y [ T. E. Dever et al., J. Biol. Chem. 269, 3212 (1994); (5)], DFFRX/Y [ M. H. Jones et al., Hum. Mol. Genet 5, 1695 (1996); (5)], DBX/Y (5), CASK/CASKP [ A. R. Cohen et al., J. Cell Biol. 142, 129 (1998); (6)], UTX/Y (5), SMCX/Y [ J. Wu et al., Hum. Mol. Genet. 3, 153 (1994); A. I. Agulnik et al., Hum. Mol. Genet. 3, 879 (1994)], RPS4X/Y [ E. M. Fisher et al., Cell 63, 1205 (1990)], RBMX/Y [ M. Soulard et al., Nucleic Acids Res. 21, 4210 (1993); K. Ma et al., Cell 75, 1287 (1993); M. L. Delbridge, P. A. Lingenfelter, C. M. Disteche, J. A. Graves, Nature Genet. 22, 223 (1999); S. Mazeyrat N. Saut, M. G. Mattel, M. J. Mitchell, Nature Genet. 22, 224 (1999)], SOX3/SRY [ M. Stevanovic, R. Lovell-Badge, J. Collignon, P. N. Goodfellow, Hum. Mol. Genet. 2, 2013 (1993); A. H. Sinclair et al., Nature 346, 240 (1990)]. One interspecies pair was also studied: human UBE1X [ P. M. Handley, M. Mueckler, N. R. Siegel, A. Ciechanover, A. L. Schwartz, Proc. Natl. Acad. Sci. U.S.A. 88, 258 (1991)] and squirrel monkey UBF1Y (29). In humans, UBE1Y was deleted from the Y chromosome (29). We used squirrel monkey UBE1Y as a substitute.
25. The 19 X-Y gene pairs studied include the following: GYG2/GYG2P [J. Mu, A. V. Skurat, P. J. Roach, J. Biol. Chem. 272, 27589 (1997); (6)]. ARSD/AKSDP, ARSE/ ARSEP [ G. Meroni et al., Hum. Mol. Genet. 5, 423 (1996)], PRKX/Y [ A. Klink et al., Hum. Mol. Genet. 4, 869 (1995); K. Schiebel et al., Hum. Mol. Genet 6, 1985 (1997)], STS/STSP (76), KAL1/KALP [ B. Franco et al., Nature 353, 529 (1991); R. Legouis et al., Cell 67, 423 (1991); (17)], AMELX/Y [ Y. Nakahori, O. Takenaka, Y. Nakagome, Genomics 9, 264 (1991)], TB4X/Y [ H. Gondo et al., J. Immunol. 139, 3840 (1987); (5)], ZFX/Y [ D. C. Page et al., Cell 51, 1091 (1987); A. Schneider-Gädicke, P. Beer-Romero, L. C. Brown, R. Nussbaum, D. C. Page, Cell 57, 1247 (1989)], EIF1AX/Y [ T. E. Dever et al., J. Biol. Chem. 269, 3212 (1994); (5)], DFFRX/Y [ M. H. Jones et al., Hum. Mol. Genet 5, 1695 (1996); (5)], DBX/Y (5), CASK/CASKP [ A. R. Cohen et al., J. Cell Biol. 142, 129 (1998); (6)], UTX/Y (5), SMCX/Y [ J. Wu et al., Hum. Mol. Genet. 3, 153 (1994); A. I. Agulnik et al., Hum. Mol. Genet. 3, 879 (1994)], RPS4X/Y [ E. M. Fisher et al., Cell 63, 1205 (1990)], RBMX/Y [ M. Soulard et al., Nucleic Acids Res. 21, 4210 (1993); K. Ma et al., Cell 75, 1287 (1993); M. L. Delbridge, P. A. Lingenfelter, C. M. Disteche, J. A. Graves, Nature Genet. 22, 223 (1999); S. Mazeyrat N. Saut, M. G. Mattel, M. J. Mitchell, Nature Genet. 22, 224 (1999)], SOX3/SRY [ M. Stevanovic, R. Lovell-Badge, J. Collignon, P. N. Goodfellow, Hum. Mol. Genet. 2, 2013 (1993); A. H. Sinclair et al., Nature 346, 240 (1990)]. One interspecies pair was also studied: human UBE1X [ P. M. Handley, M. Mueckler, N. R. Siegel, A. Ciechanover, A. L. Schwartz, Proc. Natl. Acad. Sci. U.S.A. 88, 258 (1991)] and squirrel monkey UBF1Y (29). In humans, UBE1Y was deleted from the Y chromosome (29). We used squirrel monkey UBE1Y as a substitute.
26. The 19 X-Y gene pairs studied include the following: GYG2/GYG2P [J. Mu, A. V. Skurat, P. J. Roach, J. Biol. Chem. 272, 27589 (1997); (6)]. ARSD/AKSDP, ARSE/ ARSEP [ G. Meroni et al., Hum. Mol. Genet. 5, 423 (1996)], PRKX/Y [ A. Klink et al., Hum. Mol. Genet. 4, 869 (1995); K. Schiebel et al., Hum. Mol. Genet 6, 1985 (1997)], STS/STSP (76), KAL1/KALP [ B. Franco et al., Nature 353, 529 (1991); R. Legouis et al., Cell 67, 423 (1991); (17)], AMELX/Y [ Y. Nakahori, O. Takenaka, Y. Nakagome, Genomics 9, 264 (1991)], TB4X/Y [ H. Gondo et al., J. Immunol. 139, 3840 (1987); (5)], ZFX/Y [ D. C. Page et al., Cell 51, 1091 (1987); A. Schneider-Gädicke, P. Beer-Romero, L. C. Brown, R. Nussbaum, D. C. Page, Cell 57, 1247 (1989)], EIF1AX/Y [ T. E. Dever et al., J. Biol. Chem. 269, 3212 (1994); (5)], DFFRX/Y [ M. H. Jones et al., Hum. Mol. Genet 5, 1695 (1996); (5)], DBX/Y (5), CASK/CASKP [ A. R. Cohen et al., J. Cell Biol. 142, 129 (1998); (6)], UTX/Y (5), SMCX/Y [ J. Wu et al., Hum. Mol. Genet. 3, 153 (1994); A. I. Agulnik et al., Hum. Mol. Genet. 3, 879 (1994)], RPS4X/Y [ E. M. Fisher et al., Cell 63, 1205 (1990)], RBMX/Y [ M. Soulard et al., Nucleic Acids Res. 21, 4210 (1993); K. Ma et al., Cell 75, 1287 (1993); M. L. Delbridge, P. A. Lingenfelter, C. M. Disteche, J. A. Graves, Nature Genet. 22, 223 (1999); S. Mazeyrat N. Saut, M. G. Mattel, M. J. Mitchell, Nature Genet. 22, 224 (1999)], SOX3/SRY [ M. Stevanovic, R. Lovell-Badge, J. Collignon, P. N. Goodfellow, Hum. Mol. Genet. 2, 2013 (1993); A. H. Sinclair et al., Nature 346, 240 (1990)]. One interspecies pair was also studied: human UBE1X [ P. M. Handley, M. Mueckler, N. R. Siegel, A. Ciechanover, A. L. Schwartz, Proc. Natl. Acad. Sci. U.S.A. 88, 258 (1991)] and squirrel monkey UBF1Y (29). In humans, UBE1Y was deleted from the Y chromosome (29). We used squirrel monkey UBE1Y as a substitute.
27. The 19 X-Y gene pairs studied include the following: GYG2/GYG2P [J. Mu, A. V. Skurat, P. J. Roach, J. Biol. Chem. 272, 27589 (1997); (6)]. ARSD/AKSDP, ARSE/ ARSEP [ G. Meroni et al., Hum. Mol. Genet. 5, 423 (1996)], PRKX/Y [ A. Klink et al., Hum. Mol. Genet. 4, 869 (1995); K. Schiebel et al., Hum. Mol. Genet 6, 1985 (1997)], STS/STSP (76), KAL1/KALP [ B. Franco et al., Nature 353, 529 (1991); R. Legouis et al., Cell 67, 423 (1991); (17)], AMELX/Y [ Y. Nakahori, O. Takenaka, Y. Nakagome, Genomics 9, 264 (1991)], TB4X/Y [ H. Gondo et al., J. Immunol. 139, 3840 (1987); (5)], ZFX/Y [ D. C. Page et al., Cell 51, 1091 (1987); A. Schneider-Gädicke, P. Beer-Romero, L. C. Brown, R. Nussbaum, D. C. Page, Cell 57, 1247 (1989)], EIF1AX/Y [ T. E. Dever et al., J. Biol. Chem. 269, 3212 (1994); (5)], DFFRX/Y [ M. H. Jones et al., Hum. Mol. Genet 5, 1695 (1996); (5)], DBX/Y (5), CASK/CASKP [ A. R. Cohen et al., J. Cell Biol. 142, 129 (1998); (6)], UTX/Y (5), SMCX/Y [ J. Wu et al., Hum. Mol. Genet. 3, 153 (1994); A. I. Agulnik et al., Hum. Mol. Genet. 3, 879 (1994)], RPS4X/Y [ E. M. Fisher et al., Cell 63, 1205 (1990)], RBMX/Y [ M. Soulard et al., Nucleic Acids Res. 21, 4210 (1993); K. Ma et al., Cell 75, 1287 (1993); M. L. Delbridge, P. A. Lingenfelter, C. M. Disteche, J. A. Graves, Nature Genet. 22, 223 (1999); S. Mazeyrat N. Saut, M. G. Mattel, M. J. Mitchell, Nature Genet. 22, 224 (1999)], SOX3/SRY [ M. Stevanovic, R. Lovell-Badge, J. Collignon, P. N. Goodfellow, Hum. Mol. Genet. 2, 2013 (1993); A. H. Sinclair et al., Nature 346, 240 (1990)]. One interspecies pair was also studied: human UBE1X [ P. M. Handley, M. Mueckler, N. R. Siegel, A. Ciechanover, A. L. Schwartz, Proc. Natl. Acad. Sci. U.S.A. 88, 258 (1991)] and squirrel monkey UBF1Y (29). In humans, UBE1Y was deleted from the Y chromosome (29). We used squirrel monkey UBE1Y as a substitute.
28. Using polymerase chain reaction (PCR), we tested DNAs from the 93 hybrid cell lines of the GeneBridge 4 panel (Research Genetics) [G. Gyapay et al., Hum. Mol. Genet. 5, 339 (1996)] for the presence of each of the X-linked genes. PCR conditions and primer sequences have been deposited at GenBank, where accession numbers are as follows: GYG2, G49430; ARSD, G42687; ARSE, G42688; PRKX, G42689; STS, G42690; KAL1, G42691; AMELX, G42692; TB4X, G34979; E/F1AX, G34989; ZFX, G42693; DFFRX, G34982; DBX, G34988; CASK, G49441; UTX, G34976; UBE1X, G42694; SMCX, G42695; RPS4X, AF041428; RBMX, G42696; and SOX3, G42697. Analysis of the results positioned the genes with respect to the radiation hybrid map of the X chromosome constructed at the Whitehead/MIT Center for Genome Research [ T. J. Hudson et al., Science 270, 1945 (1995); www-genome.wi.mit.edu/cgi-bin/contig/phys_map].
29. Using polymerase chain reaction (PCR), we tested DNAs from the 93 hybrid cell lines of the GeneBridge 4 panel (Research Genetics) [G. Gyapay et al., Hum. Mol. Genet. 5, 339 (1996)] for the presence of each of the X-linked genes. PCR conditions and primer sequences have been deposited at GenBank, where accession numbers are as follows: GYG2, G49430; ARSD, G42687; ARSE, G42688; PRKX, G42689; STS, G42690; KAL1, G42691; AMELX, G42692; TB4X, G34979; E/F1AX, G34989; ZFX, G42693; DFFRX, G34982; DBX, G34988; CASK, G49441; UTX, G34976; UBE1X, G42694; SMCX, G42695; RPS4X, AF041428; RBMX, G42696; and SOX3, G42697. Analysis of the results positioned the genes with respect to the radiation hybrid map of the X chromosome constructed at the Whitehead/MIT Center for Genome Research [ T. J. Hudson et al., Science 270, 1945 (1995); www-genome.wi.mit.edu/cgi-bin/contig/phys_map].
30. D. Vollrath et al., Science 258, 52 (1992).
31. B. T. Lahn and D. C. Page, Science 278, 675 (1997).
32. C. Sun et al., Nature Genet., in press.
33. A) - all corrected for multiple changes-were calculated using published algorithms (8) as implemented in GCG software (Genetics Computer Group, Madison, WI). Insertions and deletions were ignored in these calculations. In the case of SOX3 and SRY, sequence similarity is limited to, and our analysis was restricted to, the HMG box domain. Our analyses of other X-Y gene pairs employed all available coding sequences. Only a partial UBE1Y (squirrel monkey) coding sequence was available for comparison with its human X homolog. Sequences for all pseudogenes were extracted from genomic sequences: GYG2P, ARSDP, and ARSEP from BAC (bacterial artificial chromosome) done 203M13 (GenBank AC002992); STSP from BAC done NH0494J04 (GenBank AC006382); KALP from BAC done NH0292P09 (GenBank AC006370); CASKP From BAC clone 47511 (GenBank AC004474). Sequences for all other genes were obtained from published cDNAs, whose GenBank accession numbers are as follows: GYG2, U94362; ARSD, X83572; ARSE, X83573; PRKX, X85545; PRKY, Y15801; STS, M1650S; KAL1, M97252; AMELX, M86932; AMELY, M86933; TB4X, M17733; TB4Y, AF000989; ZFX, X59739; ZFY, M30607; EIF1AX, L18960; EIF1AY, AF000987; DFFRX, X98296; DFFRY, AF000986; DBX, AF000982; DBY, AF000984; CASK, AF032119; UTX, AF000992; UTY, AF000994; UBE1X, M58028; UBE1Y, AJ003105; SMCX, L25270; SMCY, U52191; RPS4X, M58458; RPS4Y, M58459; RBMX, Z23064; RBMY, X76059; SOX3, X71135; SRY, X53772.
34. W. H. Li, J. Mol. Evol. 36, 96 (1993); Molecular Evolution (Sinauer Associates, Sunderland, MA, 1997).
35. W. H. Li, J. Mol. Evol. 36, 96 (1993); Molecular Evolution (Sinauer Associates, Sunderland, MA, 1997).
36. B. O. Bengtsson and P. N. Goodfellow, Ann. Hum. Genet. 51, 57 (1987).
37. L. M. Silver, Trends Genet. 9, 250 (1993); R. H. Martin et al., Hum. Genet. 93, 135 (1994); M. Jaarola, R. H. Martin, T. Ashley, Am. J. Hum. Genet. 63, 218 (1998).
38. L. M. Silver, Trends Genet. 9, 250 (1993); R. H. Martin et al., Hum. Genet. 93, 135 (1994); M. Jaarola, R. H. Martin, T. Ashley, Am. J. Hum. Genet. 63, 218 (1998).
39. L. M. Silver, Trends Genet. 9, 250 (1993); R. H. Martin et al., Hum. Genet. 93, 135 (1994); M. Jaarola, R. H. Martin, T. Ashley, Am. J. Hum. Genet. 63, 218 (1998).
40. H. J. Blair, V. Reed, S. H. Laval, Y. Boyd, Genomics 19, 215 (1994); W. J. Murphy, S. Sun, Z.-Q. Chen, J. Pecon-Slattery, S. J. O'Brien, Genome Res., in press.
41. H. J. Blair, V. Reed, S. H. Laval, Y. Boyd, Genomics 19, 215 (1994); W. J. Murphy, S. Sun, Z.-Q. Chen, J. Pecon-Slattery, S. J. O'Brien, Genome Res., in press.
42. P. A. Weller, R. Critcher, P. N. Goodfellow, J. German, N. A. Ellis, Hum. Mol. Genet. 4, 859 (1995).
43. C. J. Brown, L. Carrel, H. F. Willard, Am. J. Hum. Genet. 60, 1333 (1997).
44. K. Jegalian and D. C. Page, Nature 394, 776 (1998).
45. A ratios, the abundance of Y pseudogenes (Table 1) suggests that absence of selective constraint is the more significant factor.
46. P. H. Yen et al., Cell 55, 1123 (1988).
47. I. del Castillo, M. Cohen-Salmon, S. Blanchard, G. Lutfalla, C. Petit, Nature Genet. 2, 305 (1992); B. Incerti et al., Nature Genet. 2, 311 (1992).
48. I. del Castillo, M. Cohen-Salmon, S. Blanchard, G. Lutfalla, C. Petit, Nature Genet. 2, 305 (1992); B. Incerti et al., Nature Genet. 2, 311 (1992).
49. R. Toder, G. A. Rappold, K. Schiebel, W. Schempp, Hum. Genet. 95, 22 (1995).
50. S. Kumar and S. B. Hedges, Nature 392, 917 (1998); M. J. Benton, Vertebrate Paleontology (Chapman & Hall, New York, 1997).
51. S. Kumar and S. B. Hedges, Nature 392, 917 (1998); M. J. Benton, Vertebrate Paleontology (Chapman & Hall, New York, 1997).
52. D. Pilbeam, Sci. Am. 250 (no. 3), 84 (1984).
53. Stratum 3: Homologs of ZFX are autosomal in marsupials (27), which diverged from placental mammals 130 Ma (19). For ZFX/Y and UTX/Y (and for UBE1X/Y and SMCX/Y, in stratum 2), we employed sequence-based phylogenetic analysis to determine if differentiation into X and Y forms had begun before or after mouse/human divergence. For each X-Y gene pair, we used GCC software to construct a phylogenetic tree relating human X, human (or monkey) Y, mouse X, and mouse Y homologs. In each of the four cases, the X homologs in human and mouse formed a branch which was distinct from a second branch formed by the Y homologs in human (or monkey) and mouse. These findings suggest that X-Y differentiation of these four gene pairs began before divergence of humans and mice. This is consistent with X-Y divergence having initiated before the placental mammalian radiation that occurred 80 to 100 Ma. Stratum 2: Distinct X- and Y-linked forms of UBE1 have been found in both placental mammals and marsupials [M. J. Mitchell, D. R. Woods, S. A. Wilcox, J. A. Graves, C. E. Bishop, Nature 359, 528 (1992)], but their homologs are autosomal in monotremes (29), which diverged from placental mammals and marsupials 170 Ma (19). Stratum 1: Distinct X- and Y-linked forms of RPS4 have been found in placental mammals and marsupials (K. Jegalian and D. C. Page, unpublished results), but their homologs are autosomal in birds, whose lineage diverged from that of mammals 300 to 350 Ma (19). Y-specific SRY sequences have been identified in both placental mammals and marsupials [J. W. Foster et al., Nature 359, 531 (1992)].
54. Stratum 3: Homologs of ZFX are autosomal in marsupials (27), which diverged from placental mammals 130 Ma (19). For ZFX/Y and UTX/Y (and for UBE1X/Y and SMCX/Y, in stratum 2), we employed sequence-based phylogenetic analysis to determine if differentiation into X and Y forms had begun before or after mouse/human divergence. For each X-Y gene pair, we used GCC software to construct a phylogenetic tree relating human X, human (or monkey) Y, mouse X, and mouse Y homologs. In each of the four cases, the X homologs in human and mouse formed a branch which was distinct from a second branch formed by the Y homologs in human (or monkey) and mouse. These findings suggest that X-Y differentiation of these four gene pairs began before divergence of humans and mice. This is consistent with X-Y divergence having initiated before the placental mammalian radiation that occurred 80 to 100 Ma. Stratum 2: Distinct X- and Y-linked forms of UBE1 have been found in both placental mammals and marsupials [M. J. Mitchell, D. R. Woods, S. A. Wilcox, J. A. Graves, C. E. Bishop, Nature 359, 528 (1992)], but their homologs are autosomal in monotremes (29), which diverged from placental mammals and marsupials 170 Ma (19). Stratum 1: Distinct X- and Y-linked forms of RPS4 have been found in placental mammals and marsupials (K. Jegalian and D. C. Page, unpublished results), but their homologs are autosomal in birds, whose lineage diverged from that of mammals 300 to 350 Ma (19). Y-specific SRY sequences have been identified in both placental mammals and marsupials [J. W. Foster et al., Nature 359, 531 (1992)].
55. A. K. Fridolfsson et al., Proc. Natl. Acad. Sci. U.S.A. 95, 8147 (1998).
56. J. W. Foster and J. A. Graves, Proc. Natl. Acad. Sci. U.S.A. 91, 1927 (1994).
57. S value between SOX3/SRY (1.25 ± 0.41) and RPS4X/Y (0.97 ± 0.16) or RBMX/Y (0.94 ± 0.15) was not statistically significant At present, any distinction between subgroups 1A and 16 is tentative.
58. H. F. Willard, Cell 86, 5 (1996).
59. H. S. Chandra, Proc. Natl. Acad. Sci. U.S.A. 82, 6947 (1985).
60. J. A. Spencer, A. H. Sinclair, J. M. Watson, J. A. Graves, Genomics 11, 339 (1991).
61. J. A. Graves, Philos. Trans. R. Soc. London Ser. B 350, 305 (1995); R. Toder and J. A. Graves, Mamm. Genome 9, 373 (1998); J. M. Watson, J. A. Spencer, J. A. Graves, M. L. Snead, E. C. Lau, Genomics 14, 785 (1992); J. A. Spencer, J. M. Watson, J. A. Graves, Genomics 9, 598 (1991).
62. J. A. Graves, Philos. Trans. R. Soc. London Ser. B 350, 305 (1995); R. Toder and J. A. Graves, Mamm. Genome 9, 373 (1998); J. M. Watson, J. A. Spencer, J. A. Graves, M. L. Snead, E. C. Lau, Genomics 14, 785 (1992); J. A. Spencer, J. M. Watson, J. A. Graves, Genomics 9, 598 (1991).
63. J. A. Graves, Philos. Trans. R. Soc. London Ser. B 350, 305 (1995); R. Toder and J. A. Graves, Mamm. Genome 9, 373 (1998); J. M. Watson, J. A. Spencer, J. A. Graves, M. L. Snead, E. C. Lau, Genomics 14, 785 (1992); J. A. Spencer, J. M. Watson, J. A. Graves, Genomics 9, 598 (1991).
64. J. A. Graves, Philos. Trans. R. Soc. London Ser. B 350, 305 (1995); R. Toder and J. A. Graves, Mamm. Genome 9, 373 (1998); J. M. Watson, J. A. Spencer, J. A. Graves, M. L. Snead, E. C. Lau, Genomics 14, 785 (1992); J. A. Spencer, J. M. Watson, J. A. Graves, Genomics 9, 598 (1991).
65. M. J. Mitchell et al., Hum. Mol. Genet. 7, 429 (1998).
66. We thank F. Lewitter for help with sequence comparisons, H. Skaletsky and T. Kawaguchi for help with database searches and analysis of mapping data, and P. Bain, D. Bartel, A. Bortvin, B. Charlesworth, D. Charlesworth, A. Chess, A. Clark, C. Disteche, G. Fink, S. Gilbert, J. Graves, R. Jaenisch, K. Jegalian, E. Lander, D. Menke, W. Rice, S. Rozen, C. Tilford, and J. Wang for discussions and comments on the manuscript Supported by NIH grant HG00257.