The complete sequence of a human Y chromosome

Arang Rhie; Sergey Nurk; Monika Cechova; Savannah J Hoyt; Dylan J Taylor; Nicolas Altemose; Paul W Hook; Sergey Koren; Mikko Rautiainen; Ivan A Alexandrov; Jamie Allen; Mobin Asri; Andrey V Bzikadze; Nae-Chyun Chen; Chen-Shan Chin; Mark Diekhans; Paul Flicek; Giulio Formenti; Arkarachai Fungtammasan; Carlos Garcia Giron; Erik Garrison; Ariel Gershman; Jennifer L Gerton; Patrick G S Grady; Andrea Guarracino; Leanne Haggerty; Reza Halabian; Nancy F Hansen; Robert Harris; Gabrielle A Hartley; William T Harvey; Marina Haukness; Jakob Heinz; Thibaut Hourlier; Robert M Hubley; Sarah E Hunt; Stephen Hwang; Miten Jain; Rupesh K Kesharwani; Alexandra P Lewis; Heng Li; Glennis A Logsdon; Julian K Lucas; Wojciech Makalowski; Christopher Markovic; Fergal J Martin; Ann M Mc Cartney; Rajiv C McCoy; Jennifer McDaniel; Brandy M McNulty; Paul Medvedev; Alla Mikheenko; Katherine M Munson; Terence D Murphy; Hugh E Olsen; Nathan D Olson; Luis F Paulin; David Porubsky; Tamara Potapova; Fedor Ryabov; Steven L Salzberg; Michael E G Sauria; Fritz J Sedlazeck; Kishwar Shafin; Valery A Shepelev; Alaina Shumate; Jessica M Storer; Likhitha Surapaneni; Angela M Taravella Oill; Françoise Thibaud-Nissen; Winston Timp; Marta Tomaszkiewicz; Mitchell R Vollger; Brian P Walenz; Allison C Watwood; Matthias H Weissensteiner; Aaron M Wenger; Melissa A Wilson; Samantha Zarate; Yiming Zhu; Justin M Zook; Evan E Eichler; Rachel J O'Neill; Michael C Schatz; Karen H Miga; Kateryna D Makova; Adam M Phillippy

doi:10.1038/s41586-023-06457-y

The complete sequence of a human Y chromosome

Nature. 2023 Sep;621(7978):344-354. doi: 10.1038/s41586-023-06457-y. Epub 2023 Aug 23.

Authors

Arang Rhie^#¹, Sergey Nurk^#^{1

2}, Monika Cechova^#^{3

4}, Savannah J Hoyt^#⁵, Dylan J Taylor^#⁶, Nicolas Altemose⁷, Paul W Hook⁸, Sergey Koren¹, Mikko Rautiainen¹, Ivan A Alexandrov^{9

10

11}, Jamie Allen¹², Mobin Asri¹³, Andrey V Bzikadze¹⁴, Nae-Chyun Chen¹⁵, Chen-Shan Chin^{16

17}, Mark Diekhans¹³, Paul Flicek^{12

18}, Giulio Formenti¹⁹, Arkarachai Fungtammasan²⁰, Carlos Garcia Giron¹², Erik Garrison²¹, Ariel Gershman⁸, Jennifer L Gerton^{22

23}, Patrick G S Grady⁵, Andrea Guarracino^{21

24}, Leanne Haggerty¹², Reza Halabian²⁵, Nancy F Hansen^{1

26}, Robert Harris²⁷, Gabrielle A Hartley⁵, William T Harvey²⁸, Marina Haukness¹³, Jakob Heinz⁸, Thibaut Hourlier¹², Robert M Hubley²⁹, Sarah E Hunt¹², Stephen Hwang³⁰, Miten Jain³¹, Rupesh K Kesharwani³², Alexandra P Lewis²⁸, Heng Li^{33

34}, Glennis A Logsdon²⁸, Julian K Lucas^{4

13}, Wojciech Makalowski²⁵, Christopher Markovic³⁵, Fergal J Martin¹², Ann M Mc Cartney¹, Rajiv C McCoy⁶, Jennifer McDaniel³⁶, Brandy M McNulty^{4

13}, Paul Medvedev^{37

38

39}, Alla Mikheenko^{10

40}, Katherine M Munson²⁸, Terence D Murphy⁴¹, Hugh E Olsen^{4

13}, Nathan D Olson³⁶, Luis F Paulin³², David Porubsky²⁸, Tamara Potapova²², Fedor Ryabov⁴², Steven L Salzberg⁴³, Michael E G Sauria⁶, Fritz J Sedlazeck^{32

44}, Kishwar Shafin⁴⁵, Valery A Shepelev⁴⁶, Alaina Shumate⁸, Jessica M Storer²⁹, Likhitha Surapaneni¹², Angela M Taravella Oill⁴⁷, Françoise Thibaud-Nissen⁴¹, Winston Timp⁸, Marta Tomaszkiewicz^{27

48}, Mitchell R Vollger²⁸, Brian P Walenz¹, Allison C Watwood²⁷, Matthias H Weissensteiner²⁷, Aaron M Wenger⁴⁹, Melissa A Wilson⁴⁷, Samantha Zarate¹⁵, Yiming Zhu³², Justin M Zook³⁶, Evan E Eichler^{28

50}, Rachel J O'Neill^{5

51

52}, Michael C Schatz^{6

15}, Karen H Miga^{4

13}, Kateryna D Makova²⁷, Adam M Phillippy⁵³

Affiliations

¹ Genome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
² Oxford Nanopore Technologies Inc., Oxford, UK.
³ Faculty of Informatics, Masaryk University, Brno, Czech Republic.
⁴ Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA, USA.
⁵ Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA.
⁶ Department of Biology, Johns Hopkins University, Baltimore, MD, USA.
⁷ Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
⁸ Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
⁹ Federal Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russia.
¹⁰ Center for Algorithmic Biotechnology, Saint Petersburg State University, St Petersburg, Russia.
¹¹ Department of Anatomy and Anthropology and Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel.
¹² European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
¹³ UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA.
¹⁴ Graduate Program in Bioinformatics and Systems Biology, University of California, San Diego, CA, USA.
¹⁵ Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA.
¹⁶ GeneDX Holdings Corp, Stamford, CT, USA.
¹⁷ Foundation of Biological Data Science, Belmont, CA, USA.
¹⁸ Department of Genetics, University of Cambridge, Cambridge, UK.
¹⁹ The Rockefeller University, New York, NY, USA.
²⁰ DNAnexus, Inc., Mountain View, CA, USA.
²¹ Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN, USA.
²² Stowers Institute for Medical Research, Kansas City, MO, USA.
²³ University of Kansas Medical Center, Kansas City, MO, USA.
²⁴ Genomics Research Centre, Human Technopole, Milan, Italy.
²⁵ Institute of Bioinformatics, Faculty of Medicine, University of Münster, Münster, Germany.
²⁶ Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
²⁷ Department of Biology, Pennsylvania State University, University Park, PA, USA.
²⁸ Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
²⁹ Institute for Systems Biology, Seattle, WA, USA.
³⁰ XDBio Program, Johns Hopkins University, Baltimore, MD, USA.
³¹ Department of Bioengineering, Department of Physics, Northeastern University, Boston, MA, USA.
³² Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA.
³³ Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA.
³⁴ Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
³⁵ Genome Technology Access Center at the McDonnell Genome Institute, Washington University, St. Louis, MO, USA.
³⁶ Biosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD, USA.
³⁷ Department of Computer Science and Engineering, Pennsylvania State University, University Park, PA, USA.
³⁸ Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA, USA.
³⁹ Center for Computational Biology and Bioinformatics, Pennsylvania State University, University Park, PA, USA.
⁴⁰ UCL Queen Square Institute of Neurology, UCL, London, UK.
⁴¹ National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
⁴² Masters Program in National Research University Higher School of Economics, Moscow, Russia.
⁴³ Departments of Biomedical Engineering, Computer Science, and Biostatistics, Johns Hopkins University, Baltimore, MD, USA.
⁴⁴ Department of Computer Science, Rice University, Houston, TX, USA.
⁴⁵ Google Inc., Mountain View, CA, USA.
⁴⁶ Institute of Molecular Genetics, Moscow, Russia.
⁴⁷ Center for Evolution and Medicine, School of Life Sciences, Arizona State University, Tempe, AZ, USA.
⁴⁸ Department of Biomedical Engineering, Pennsylvania State University, State College, PA, USA.
⁴⁹ Pacific Biosciences, Menlo Park, CA, USA.
⁵⁰ Investigator, Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA.
⁵¹ Institute for Systems Genomics, University of Connecticut, Storrs, CT, USA.
⁵² Department of Genetics and Genome Sciences, UConn Health, Farmington, CT, USA.
⁵³ Genome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. [email protected].

^# Contributed equally.

Abstract

The human Y chromosome has been notoriously difficult to sequence and assemble because of its complex repeat structure that includes long palindromes, tandem repeats and segmental duplications^1-3. As a result, more than half of the Y chromosome is missing from the GRCh38 reference sequence and it remains the last human chromosome to be finished^4,5. Here, the Telomere-to-Telomere (T2T) consortium presents the complete 62,460,029-base-pair sequence of a human Y chromosome from the HG002 genome (T2T-Y) that corrects multiple errors in GRCh38-Y and adds over 30 million base pairs of sequence to the reference, showing the complete ampliconic structures of gene families TSPY, DAZ and RBMY; 41 additional protein-coding genes, mostly from the TSPY family; and an alternating pattern of human satellite 1 and 3 blocks in the heterochromatic Yq12 region. We have combined T2T-Y with a previous assembly of the CHM13 genome⁴ and mapped available population variation, clinical variants and functional genomics data to produce a complete and comprehensive reference sequence for all 24 human chromosomes.

MeSH terms

Base Sequence
Chromosomes, Human, Y* / genetics
DNA, Satellite / genetics
Genetic Variation / genetics
Genetics, Population
Genomics* / methods
Genomics* / standards
Heterochromatin / genetics
Humans
Multigene Family / genetics
Reference Standards
Segmental Duplications, Genomic / genetics
Sequence Analysis, DNA* / standards
Tandem Repeat Sequences / genetics
Telomere / genetics

Substances

DNA, Satellite
Heterochromatin
TSPY1 protein, human
RBMY1A1 protein, human
DAZ1 protein, human

Abstract

MeSH terms

Substances

Grants and funding