Assembly of 43 human Y chromosomes reveals extensive complexity and variation

Human Genome Structural Variation Consortium (HGSVC); Pille Hallast; Peter Ebert; Mark Loftus; Feyza Yilmaz; Peter A. Audano; Glennis A. Logsdon; Marc Jan Bonder; Weichen Zhou; Wolfram Höps; Kwondo Kim; Chong Li; Savannah J. Hoyt; Philip C. Dishuck; David Porubsky; Fotios Tsetsos; Jee Young Kwon; Qihui Zhu; Katherine M. Munson; Patrick Hasenfeld; William T. Harvey; Alexandra P. Lewis; Jennifer Kordosky; Kendra Hoekzema; Rachel J. O’Neill; Jan O. Korbel; Chris Tyler-Smith; Evan E. Eichler; Xinghua Shi; Christine R. Beck; Tobias Marschall; Miriam K. Konkel; Charles Lee

doi:10.1038/s41586-023-06425-6

Assembly of 43 human Y chromosomes reveals extensive complexity and variation

Human Genome Structural Variation Consortium (HGSVC), Pille Hallast, Peter Ebert, Mark Loftus, Feyza Yilmaz, Peter A. Audano, Glennis A. Logsdon, Marc Jan Bonder, Weichen Zhou, Wolfram Höps, Kwondo Kim, Chong Li, Savannah J. Hoyt, Philip C. Dishuck, David Porubsky, Fotios Tsetsos, Jee Young Kwon, Qihui Zhu, Katherine M. Munson, Patrick HasenfeldWilliam T. Harvey, Alexandra P. Lewis, Jennifer Kordosky, Kendra Hoekzema, Rachel J. O’Neill, Jan O. Korbel, Chris Tyler-Smith, Evan E. Eichler, Xinghua Shi, Christine R. Beck, Tobias Marschall, Miriam K. Konkel, Charles Lee^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

The prevalence of highly repetitive sequences within the human Y chromosome has prevented its complete assembly to date¹ and led to its systematic omission from genomic analyses. Here we present de novo assemblies of 43 Y chromosomes spanning 182,900 years of human evolution and report considerable diversity in size and structure. Half of the male-specific euchromatic region is subject to large inversions with a greater than twofold higher recurrence rate compared with all other chromosomes². Ampliconic sequences associated with these inversions show differing mutation rates that are sequence context dependent, and some ampliconic genes exhibit evidence for concerted evolution with the acquisition and purging of lineage-specific pseudogenes. The largest heterochromatic region in the human genome, Yq12, is composed of alternating repeat arrays that show extensive variation in the number, size and distribution, but retain a 1:1 copy-number ratio. Finally, our data suggest that the boundary between the recombining pseudoautosomal region 1 and the non-recombining portions of the X and Y chromosomes lies 500 kb away from the currently established¹ boundary. The availability of fully sequence-resolved Y chromosomes from multiple individuals provides a unique opportunity for identifying new associations of traits with specific Y-chromosomal variants and garnering insights into the evolution and function of complex regions of the human genome.

Original language	English
Pages (from-to)	355-364
Number of pages	10
Journal	Nature
Volume	621
DOIs	https://doi.org/10.1038/s41586-023-06425-6
Publication status	Published - 14-Sept-2023

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Human Genome Structural Variation Consortium (HGSVC), Hallast, P., Ebert, P., Loftus, M., Yilmaz, F., Audano, P. A., Logsdon, G. A., Bonder, M. J., Zhou, W., Höps, W., Kim, K., Li, C., Hoyt, S. J., Dishuck, P. C., Porubsky, D., Tsetsos, F., Kwon, J. Y., Zhu, Q., Munson, K. M., ... Lee, C. (2023). Assembly of 43 human Y chromosomes reveals extensive complexity and variation. Nature, 621, 355-364. https://doi.org/10.1038/s41586-023-06425-6

@article{5be160ce90ad4f0fb729388b6f212e80,

title = "Assembly of 43 human Y chromosomes reveals extensive complexity and variation",

abstract = "The prevalence of highly repetitive sequences within the human Y chromosome has prevented its complete assembly to date1 and led to its systematic omission from genomic analyses. Here we present de novo assemblies of 43 Y chromosomes spanning 182,900 years of human evolution and report considerable diversity in size and structure. Half of the male-specific euchromatic region is subject to large inversions with a greater than twofold higher recurrence rate compared with all other chromosomes2. Ampliconic sequences associated with these inversions show differing mutation rates that are sequence context dependent, and some ampliconic genes exhibit evidence for concerted evolution with the acquisition and purging of lineage-specific pseudogenes. The largest heterochromatic region in the human genome, Yq12, is composed of alternating repeat arrays that show extensive variation in the number, size and distribution, but retain a 1:1 copy-number ratio. Finally, our data suggest that the boundary between the recombining pseudoautosomal region 1 and the non-recombining portions of the X and Y chromosomes lies 500 kb away from the currently established1 boundary. The availability of fully sequence-resolved Y chromosomes from multiple individuals provides a unique opportunity for identifying new associations of traits with specific Y-chromosomal variants and garnering insights into the evolution and function of complex regions of the human genome.",

author = "{Human Genome Structural Variation Consortium (HGSVC)} and Pille Hallast and Peter Ebert and Mark Loftus and Feyza Yilmaz and Audano, {Peter A.} and Logsdon, {Glennis A.} and Bonder, {Marc Jan} and Weichen Zhou and Wolfram H{\"o}ps and Kwondo Kim and Chong Li and Hoyt, {Savannah J.} and Dishuck, {Philip C.} and David Porubsky and Fotios Tsetsos and Kwon, {Jee Young} and Qihui Zhu and Munson, {Katherine M.} and Patrick Hasenfeld and Harvey, {William T.} and Lewis, {Alexandra P.} and Jennifer Kordosky and Kendra Hoekzema and O{\textquoteright}Neill, {Rachel J.} and Korbel, {Jan O.} and Chris Tyler-Smith and Eichler, {Evan E.} and Xinghua Shi and Beck, {Christine R.} and Tobias Marschall and Konkel, {Miriam K.} and Charles Lee",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2023",

month = sep,

day = "14",

doi = "10.1038/s41586-023-06425-6",

language = "English",

volume = "621",

pages = "355--364",

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Human Genome Structural Variation Consortium (HGSVC), Hallast, P, Ebert, P, Loftus, M, Yilmaz, F, Audano, PA, Logsdon, GA, Bonder, MJ, Zhou, W, Höps, W, Kim, K, Li, C, Hoyt, SJ, Dishuck, PC, Porubsky, D, Tsetsos, F, Kwon, JY, Zhu, Q, Munson, KM, Hasenfeld, P, Harvey, WT, Lewis, AP, Kordosky, J, Hoekzema, K, O’Neill, RJ, Korbel, JO, Tyler-Smith, C, Eichler, EE, Shi, X, Beck, CR, Marschall, T, Konkel, MK & Lee, C 2023, 'Assembly of 43 human Y chromosomes reveals extensive complexity and variation', Nature, vol. 621, pp. 355-364. https://doi.org/10.1038/s41586-023-06425-6

TY - JOUR

T1 - Assembly of 43 human Y chromosomes reveals extensive complexity and variation

AU - Human Genome Structural Variation Consortium (HGSVC)

AU - Hallast, Pille

AU - Ebert, Peter

AU - Loftus, Mark

AU - Yilmaz, Feyza

AU - Audano, Peter A.

AU - Logsdon, Glennis A.

AU - Bonder, Marc Jan

AU - Zhou, Weichen

AU - Höps, Wolfram

AU - Kim, Kwondo

AU - Li, Chong

AU - Hoyt, Savannah J.

AU - Dishuck, Philip C.

AU - Porubsky, David

AU - Tsetsos, Fotios

AU - Kwon, Jee Young

AU - Zhu, Qihui

AU - Munson, Katherine M.

AU - Hasenfeld, Patrick

AU - Harvey, William T.

AU - Lewis, Alexandra P.

AU - Kordosky, Jennifer

AU - Hoekzema, Kendra

AU - O’Neill, Rachel J.

AU - Korbel, Jan O.

AU - Tyler-Smith, Chris

AU - Eichler, Evan E.

AU - Shi, Xinghua

AU - Beck, Christine R.

AU - Marschall, Tobias

AU - Konkel, Miriam K.

AU - Lee, Charles

PY - 2023/9/14

Y1 - 2023/9/14

N2 - The prevalence of highly repetitive sequences within the human Y chromosome has prevented its complete assembly to date1 and led to its systematic omission from genomic analyses. Here we present de novo assemblies of 43 Y chromosomes spanning 182,900 years of human evolution and report considerable diversity in size and structure. Half of the male-specific euchromatic region is subject to large inversions with a greater than twofold higher recurrence rate compared with all other chromosomes2. Ampliconic sequences associated with these inversions show differing mutation rates that are sequence context dependent, and some ampliconic genes exhibit evidence for concerted evolution with the acquisition and purging of lineage-specific pseudogenes. The largest heterochromatic region in the human genome, Yq12, is composed of alternating repeat arrays that show extensive variation in the number, size and distribution, but retain a 1:1 copy-number ratio. Finally, our data suggest that the boundary between the recombining pseudoautosomal region 1 and the non-recombining portions of the X and Y chromosomes lies 500 kb away from the currently established1 boundary. The availability of fully sequence-resolved Y chromosomes from multiple individuals provides a unique opportunity for identifying new associations of traits with specific Y-chromosomal variants and garnering insights into the evolution and function of complex regions of the human genome.

AB - The prevalence of highly repetitive sequences within the human Y chromosome has prevented its complete assembly to date1 and led to its systematic omission from genomic analyses. Here we present de novo assemblies of 43 Y chromosomes spanning 182,900 years of human evolution and report considerable diversity in size and structure. Half of the male-specific euchromatic region is subject to large inversions with a greater than twofold higher recurrence rate compared with all other chromosomes2. Ampliconic sequences associated with these inversions show differing mutation rates that are sequence context dependent, and some ampliconic genes exhibit evidence for concerted evolution with the acquisition and purging of lineage-specific pseudogenes. The largest heterochromatic region in the human genome, Yq12, is composed of alternating repeat arrays that show extensive variation in the number, size and distribution, but retain a 1:1 copy-number ratio. Finally, our data suggest that the boundary between the recombining pseudoautosomal region 1 and the non-recombining portions of the X and Y chromosomes lies 500 kb away from the currently established1 boundary. The availability of fully sequence-resolved Y chromosomes from multiple individuals provides a unique opportunity for identifying new associations of traits with specific Y-chromosomal variants and garnering insights into the evolution and function of complex regions of the human genome.

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U2 - 10.1038/s41586-023-06425-6

DO - 10.1038/s41586-023-06425-6

M3 - Article

C2 - 37612510

AN - SCOPUS:85168579739

SN - 0028-0836

VL - 621

SP - 355

EP - 364

JO - Nature

JF - Nature

ER -

Assembly of 43 human Y chromosomes reveals extensive complexity and variation

Abstract

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