New Results
Complete genomic and epigenetic maps of human centromeres
View ORCID ProfileNicolas Altemose, View ORCID ProfileGlennis A. Logsdon, View ORCID ProfileAndrey V. Bzikadze, View ORCID ProfilePragya Sidhwani, View ORCID ProfileSasha A. Langley, View ORCID ProfileGina V. Caldas, Savannah J. Hoyt, View ORCID ProfileLev Uralsky, Fedor D. Ryabov, View ORCID ProfileColin J. Shew, View ORCID ProfileMichael E.G. Sauria, View ORCID ProfileMatthew Borchers, View ORCID ProfileAriel Gershman, View ORCID ProfileAlla Mikheenko, Valery A. Shepelev, View ORCID ProfileTatiana Dvorkina, View ORCID ProfileOlga Kunyavskaya, View ORCID ProfileMitchell R. Vollger, View ORCID ProfileArang Rhie, View ORCID ProfileAnn M. McCartney, View ORCID ProfileMobin Asri, View ORCID ProfileRyan Lorig-Roach, View ORCID ProfileKishwar Shafin, View ORCID ProfileSergey Aganezov, Daniel Olson, Leonardo Gomes de Lima, Tamara Potapova, Gabrielle A. Hartley, View ORCID ProfileMarina Haukness, View ORCID ProfilePeter Kerpedjiev, Fedor Gusev, Kristof Tigyi, Shelise Brooks, Alice Young, View ORCID ProfileSergey Nurk, View ORCID ProfileSergey Koren, View ORCID ProfileSofie R. Salama, View ORCID ProfileBenedict Paten, View ORCID ProfileEvgeny I. Rogaev, View ORCID ProfileAaron Streets, View ORCID ProfileGary H. Karpen, View ORCID ProfileAbby F. Dernburg, View ORCID ProfileBeth A. Sullivan, View ORCID ProfileAaron F. Straight, View ORCID ProfileTravis J. Wheeler, View ORCID ProfileJennifer L. Gerton, View ORCID ProfileEvan E. Eichler, View ORCID ProfileAdam M. Phillippy, View ORCID ProfileWinston Timp, View ORCID ProfileMegan Y. Dennis, View ORCID ProfileRachel J. O’Neill, View ORCID ProfileJustin M. Zook, Michael C. Schatz, View ORCID ProfilePavel A. Pevzner, View ORCID ProfileMark Diekhans, View ORCID ProfileCharles H. Langley, Ivan A. Alexandrov, Karen H. Miga
doi: https://doi.org/10.1101/2021.07.12.452052
Nicolas Altemose
1Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA
Glennis A. Logsdon
2Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA
Andrey V. Bzikadze
3Graduate Program in Bioinformatics and Systems Biology, University of California San Diego, La Jolla, CA, USA
Pragya Sidhwani
4Department of Biochemistry, Stanford University, Stanford, California, USA
Sasha A. Langley
1Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA
Gina V. Caldas
1Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA
Savannah J. Hoyt
5Institute for Systems Genomics, University of Connecticut, Storrs, CT, USA
6Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA
Lev Uralsky
7Sirius University of Science and Technology, Sochi, Russia
8Vavilov Institute of General Genetics, Moscow, Russia
Fedor D. Ryabov
9Moscow Polytechnic University, Moscow, Russia
Colin J. Shew
10Genome Center, MIND Institute, and Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, Davis, CA, USA
Michael E.G. Sauria
11Department of Biology, Johns Hopkins University, Baltimore, MD, USA
Matthew Borchers
12Stowers Institute for Medical Research, Kansas City, MO, USA
Ariel Gershman
13Department of Molecular Biology and Genetics, Johns Hopkins University, Baltimore, MD, USA
Alla Mikheenko
14Center for Algorithmic Biotechnology, Institute of Translational Biomedicine, Saint Petersburg State University, Saint Petersburg, Russia
Valery A. Shepelev
8Vavilov Institute of General Genetics, Moscow, Russia
Tatiana Dvorkina
14Center for Algorithmic Biotechnology, Institute of Translational Biomedicine, Saint Petersburg State University, Saint Petersburg, Russia
Olga Kunyavskaya
14Center for Algorithmic Biotechnology, Institute of Translational Biomedicine, Saint Petersburg State University, Saint Petersburg, Russia
Mitchell R. Vollger
2Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA
Arang Rhie
15Genome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
Ann M. McCartney
15Genome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
Mobin Asri
16UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA
Ryan Lorig-Roach
16UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA
Kishwar Shafin
16UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA
Sergey Aganezov
17Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA
Daniel Olson
18Department of Computer Science, University of Montana, Missoula, MT
Leonardo Gomes de Lima
12Stowers Institute for Medical Research, Kansas City, MO, USA
Tamara Potapova
12Stowers Institute for Medical Research, Kansas City, MO, USA
Gabrielle A. Hartley
5Institute for Systems Genomics, University of Connecticut, Storrs, CT, USA
6Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA
Marina Haukness
16UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA
Peter Kerpedjiev
19Reservoir Genomics LLC, Oakland, CA
Fedor Gusev
8Vavilov Institute of General Genetics, Moscow, Russia
Kristof Tigyi
16UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA
20Howard Hughes Medical Institute, Chevy Chase, MD, USA
Shelise Brooks
21NIH Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
Alice Young
21NIH Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
Sergey Nurk
15Genome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
Sergey Koren
15Genome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
Sofie R. Salama
16UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA
20Howard Hughes Medical Institute, Chevy Chase, MD, USA
Benedict Paten
16UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA
34Department of Biomolecular Engineering, University of California Santa Cruz, CA, USA
Evgeny I. Rogaev
7Sirius University of Science and Technology, Sochi, Russia
8Vavilov Institute of General Genetics, Moscow, Russia
22Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA, USA
23Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia
Aaron Streets
24Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA
25Chan Zuckerberg Biohub, San Francisco, CA, USA
Gary H. Karpen
1Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA
26BioEngineering & BioMedical Sciences Department, Lawrence Berkeley National Laboratory, Berkeley, CA, USA
Abby F. Dernburg
1Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA
27Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA, US
20Howard Hughes Medical Institute, Chevy Chase, MD, USA
Beth A. Sullivan
28Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA
Aaron F. Straight
4Department of Biochemistry, Stanford University, Stanford, California, USA
Travis J. Wheeler
18Department of Computer Science, University of Montana, Missoula, MT
Jennifer L. Gerton
12Stowers Institute for Medical Research, Kansas City, MO, USA
Evan E. Eichler
2Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA
20Howard Hughes Medical Institute, Chevy Chase, MD, USA
Adam M. Phillippy
15Genome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
Winston Timp
13Department of Molecular Biology and Genetics, Johns Hopkins University, Baltimore, MD, USA
29Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA
Megan Y. Dennis
10Genome Center, MIND Institute, and Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, Davis, CA, USA
Rachel J. O’Neill
5Institute for Systems Genomics, University of Connecticut, Storrs, CT, USA
6Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA
Justin M. Zook
30Biosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD
Michael C. Schatz
17Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA
Pavel A. Pevzner
31Department of Computer Science and Engineering, University of California at San Diego, San Diego, CA, USA
Mark Diekhans
16UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA
Charles H. Langley
32Department of Evolution and Ecology, University of California Davis, Davis, CA, USA
Ivan A. Alexandrov
8Vavilov Institute of General Genetics, Moscow, Russia
14Center for Algorithmic Biotechnology, Institute of Translational Biomedicine, Saint Petersburg State University, Saint Petersburg, Russia
33Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russia
Karen H. Miga
16UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA
34Department of Biomolecular Engineering, University of California Santa Cruz, CA, USA
Abstract
Existing human genome assemblies have almost entirely excluded highly repetitive sequences within and near centromeres, limiting our understanding of their sequence, evolution, and essential role in chromosome segregation. Here, we present an extensive study of newly assembled peri/centromeric sequences representing 6.2% (189.9 Mb) of the first complete, telomere-to-telomere human genome assembly (T2T-CHM13). We discovered novel patterns of peri/centromeric repeat organization, variation, and evolution at both large and small length scales. We also found that inner kinetochore proteins tend to overlap the most recently duplicated subregions within centromeres. Finally, we compared chromosome X centromeres across a diverse panel of individuals and uncovered structural, epigenetic, and sequence variation at single-base resolution across these regions. In total, this work provides an unprecedented atlas of human centromeres to guide future studies of their complex and critical functions as well as their unique evolutionary dynamics.
One-sentence summary Deep characterization of fully assembled human centromeres reveals their architecture and fine-scale organization, variation, and evolution.
Competing Interest Statement
SK and KHM have received travel funds to speak at symposia organized by Oxford Nanopore. W.T. has two patents (8,748,091 and 8,394,584) licensed to Oxford Nanopore Technologies.
Copyright
The copyright holder has placed this preprint in the Public Domain. It is no longer restricted by copyright. Anyone can legally share, reuse, remix, or adapt this material for any purpose without crediting the original authors.
Posted July 13, 2021.
Complete genomic and epigenetic maps of human centromeres
Nicolas Altemose, Glennis A. Logsdon, Andrey V. Bzikadze, Pragya Sidhwani, Sasha A. Langley, Gina V. Caldas, Savannah J. Hoyt, Lev Uralsky, Fedor D. Ryabov, Colin J. Shew, Michael E.G. Sauria, Matthew Borchers, Ariel Gershman, Alla Mikheenko, Valery A. Shepelev, Tatiana Dvorkina, Olga Kunyavskaya, Mitchell R. Vollger, Arang Rhie, Ann M. McCartney, Mobin Asri, Ryan Lorig-Roach, Kishwar Shafin, Sergey Aganezov, Daniel Olson, Leonardo Gomes de Lima, Tamara Potapova, Gabrielle A. Hartley, Marina Haukness, Peter Kerpedjiev, Fedor Gusev, Kristof Tigyi, Shelise Brooks, Alice Young, Sergey Nurk, Sergey Koren, Sofie R. Salama, Benedict Paten, Evgeny I. Rogaev, Aaron Streets, Gary H. Karpen, Abby F. Dernburg, Beth A. Sullivan, Aaron F. Straight, Travis J. Wheeler, Jennifer L. Gerton, Evan E. Eichler, Adam M. Phillippy, Winston Timp, Megan Y. Dennis, Rachel J. O’Neill, Justin M. Zook, Michael C. Schatz, Pavel A. Pevzner, Mark Diekhans, Charles H. Langley, Ivan A. Alexandrov, Karen H. Miga
bioRxiv 2021.07.12.452052; doi: https://doi.org/10.1101/2021.07.12.452052
Complete genomic and epigenetic maps of human centromeres
Nicolas Altemose, Glennis A. Logsdon, Andrey V. Bzikadze, Pragya Sidhwani, Sasha A. Langley, Gina V. Caldas, Savannah J. Hoyt, Lev Uralsky, Fedor D. Ryabov, Colin J. Shew, Michael E.G. Sauria, Matthew Borchers, Ariel Gershman, Alla Mikheenko, Valery A. Shepelev, Tatiana Dvorkina, Olga Kunyavskaya, Mitchell R. Vollger, Arang Rhie, Ann M. McCartney, Mobin Asri, Ryan Lorig-Roach, Kishwar Shafin, Sergey Aganezov, Daniel Olson, Leonardo Gomes de Lima, Tamara Potapova, Gabrielle A. Hartley, Marina Haukness, Peter Kerpedjiev, Fedor Gusev, Kristof Tigyi, Shelise Brooks, Alice Young, Sergey Nurk, Sergey Koren, Sofie R. Salama, Benedict Paten, Evgeny I. Rogaev, Aaron Streets, Gary H. Karpen, Abby F. Dernburg, Beth A. Sullivan, Aaron F. Straight, Travis J. Wheeler, Jennifer L. Gerton, Evan E. Eichler, Adam M. Phillippy, Winston Timp, Megan Y. Dennis, Rachel J. O’Neill, Justin M. Zook, Michael C. Schatz, Pavel A. Pevzner, Mark Diekhans, Charles H. Langley, Ivan A. Alexandrov, Karen H. Miga
bioRxiv 2021.07.12.452052; doi: https://doi.org/10.1101/2021.07.12.452052
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