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 journalArticleAcademicpeer-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 languageEnglish
    Pages (from-to)355-364
    Number of pages10
    JournalNature
    Volume621
    DOIs
    Publication statusPublished - 14-Sept-2023

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    • Assembly of 43 human Y chromosomes reveals extensive complexity and variation

      Hallast, P. (Creator), Ebert, P. (Creator), Loftus, M. (Creator), Yilmaz, F. (Creator), Audano, P. A. (Creator), Logsdon, G. A. (Creator), Bonder, M. J. (Creator), Zhou, W. (Creator), Höps, W. (Creator), Kim, K. (Creator), Li, C. (Creator), Dishuck, P. C. (Creator), Porubsky, D. (Creator), Tsetsos, F. (Creator), Kwon, J. Y. (Creator), Zhu, Q. (Creator), Munson, K. M. (Creator), Hasenfeld, P. (Creator), Harvey, W. T. (Creator), Lewis, A. P. (Creator), Kordosky, J. (Creator), Hoekzema, K. (Creator), Korbel, J. O. (Creator), Tyler-Smith, C. (Creator), Eichler, E. E. (Creator), Shi, X. (Creator), Beck, C. R. (Creator), Marschall, T. (Creator), Konkel, M. K. (Creator), Lee, C. (Creator), Hoyt, S. J. (Creator) & O’Neill, R. J. (Creator), Springer, 29-Sept-2023

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