Complete genomic and epigenetic maps of human centromeres
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Abstract
Existing human genome assemblies have almost entirely excluded repetitive sequences within and near centromeres, limiting our understanding of their organization, evolution, and functions, which include facilitating proper chromosome segregation. Now, a complete, telomere-to-telomere human genome assembly (T2T-CHM13) has enabled us to comprehensively characterize pericentromeric and centromeric repeats, which constitute 6.2% of the genome (189.9 megabases). Detailed maps of these regions revealed multimegabase structural rearrangements, including in active centromeric repeat arrays. Analysis of centromere-associated sequences uncovered a strong relationship between the position of the centromere and the evolution of the surrounding DNA through layered repeat expansions. Furthermore, comparisons of chromosome X centromeres across a diverse panel of individuals illuminated high degrees of structural, epigenetic, and sequence variation in these complex and rapidly evolving regions.
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“…of these regions are peri/centromeric (Supplementary Figure 3), with the active/inactive alpha satellites and human satellite 3 comprising about ∼50% of these bases, mainly due to their highly repetitive composition and also higher frequency compared to other satellites (Altemose et al., 2022).”
BackgroundSelf-citationA complete reference genome improves analysis of human genetic variation
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Fragile sites, chromosomal lesions, tandem repeats, and disease
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- Authors
- Altemose, N., Logsdon, G. A., Bzikadze, A. V., Sidhwani, P., Langley, S. A., Caldas, G. V., Hoyt, S. J., Uralsky, L., Ryabov, F. D., Shew, C. J., Sauria, M. E. G., Borchers, M., Gershman, A., Mikheenko, A., Shepelev, V. A., Dvorkina, T., Kunyavskaya, O., Vollger, M. R., Rhie, A., McCartney, A. M., Asri, M., Lorig-Roach, R., Shafin, K., Lucas, J. K., Aganezov, S., Olson, D., de Lima, L. G., Potapova, T., Hartley, G. A., Haukness, M., Kerpedjiev, P., Gusev, F., Tigyi, K., Brooks, S., Young, A., Nurk, S., Koren, S., Salama, S. R., Paten, B., Rogaev, E. I., Streets, A., Karpen, G. H., Dernburg, A. F., Sullivan, B. A., Straight, A. F., Wheeler, T. J., Gerton, J. L., Eichler, E. E., Phillippy, A. M., Timp, W., Dennis, M. Y., O’Neill, R. J., Zook, J. M., Schatz, M. C., Pevzner, P. A., Diekhans, M., Langley, C. H., Alexandrov, I. A., & Miga, K. H.
- Affiliations
- University of California, Berkeley (US)
- University of Washington (US)
- University of California San Diego (US)
- Stanford University (US)
- University of Connecticut (US)
- Sirius University of Science and Technology (RU)
- Moscow Polytechnic University (RU)
- University of California, Davis (US)
- Johns Hopkins University (US)
- Stowers Institute for Medical Research (US)
- St Petersburg University (RU)
- Vavilov Institute of General Genetics (RU)
- National Institutes of Health (US)
- Genome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
- University of California, Santa Cruz (US)
- University of Montana (US)
- Stowers Institute for Medical Research, Kansas City, MO, USA.
- Reservoir Genomics, Oakland, CA.
- Howard Hughes Medical Institute (US)
- University of Massachusetts Chan Medical School (US)
- Chan Zuckerberg Biohub San Francisco (US)
- Lawrence Berkeley National Laboratory (US)
- QB3 (US)
- Duke University (US)
- Institute for Systems Genomics, University of Connecticut, Storrs, CT, USA.
- National Institute of Standards and Technology (US)
- Russian Academy of Sciences (RU)
- Corresponding author
- Logsdon, Glennis A.
- Bzikadze, Andrey V.
- Sidhwani, Pragya
- Langley, Sasha A.
- Caldas, Gina V.
- Alexandrov, Ivan A.
- Miga, Karen H.
- ORCID
- Altemose, Nicolas
- Logsdon, Glennis A.
- Bzikadze, Andrey V.
- Sidhwani, Pragya
- Langley, Sasha A.
- Caldas, Gina V.
- Hoyt, Savannah J.
- Uralsky, Lev
- Ryabov, Fedor D.
- Shew, Colin J.
- Sauria, Michael E. G.
- Borchers, Matthew
- Gershman, Ariel
- Mikheenko, Alla
- Dvorkina, Tatiana
- Kunyavskaya, Olga
- Vollger, Mitchell R.
- Rhie, Arang
- Asri, Mobin
- Lorig-Roach, Ryan
- Shafin, Kishwar
- Lucas, Julian K.
- Aganezov, Sergey
- Olson, Daniel
- de Lima, Leonardo Gomes
- Potapova, Tamara
- Hartley, Gabrielle A.
- Haukness, Marina
- Kerpedjiev, Peter
- Gusev, Fedor
- Brooks, Shelise
- Young, Alice
- Nurk, Sergey
- Koren, Sergey
- Salama, Sofie R.
- Paten, Benedict
- Rogaev, Evgeny I.
- Streets, Aaron
- Karpen, Gary H.
- Dernburg, Abby F.
- Sullivan, Beth A.
- Straight, Aaron F.
- Wheeler, Travis J.
- Gerton, Jennifer L.
- Eichler, Evan E.
- Phillippy, Adam M.
- Timp, Winston
- Dennis, Megan Y.
- O’Neill, Rachel J.
- Zook, Justin M.
- Schatz, Michael C.
- Pevzner, Pavel A.
- Diekhans, Mark
- Langley, Charles H.
- Alexandrov, Ivan A.
- Miga, Karen H.
- Venue
- Science
- Published
- 2022-04
- Volume
- 376
- Issue
- 6588
- Pages
- eabl4178-eabl4178
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC9233505
- OpenAlex
- W4220937793
- Cited by
- 618
- References
- 164
- Citations by year
- 2026: 127 · 2025: 160 · 2024: 139 · 2023: 119 · 2022: 65 · 2021: 8
- FWCI
- 69.95
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- public-domain
- Locations
- Science (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, public-domain)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Science Foundation (1732253, 1627442, 1643825, 1613806, P20GM103546, 1758800)
- Howard Hughes Medical Institute
- Damon Runyon Cancer Research Foundation
- Russian Foundation for Basic Research (18-29-, 18-29-13051)
- Saint Petersburg State University (51555639, PURE 51555639)
- Russian Science Foundation (19-75-30039)
- National Institutes of Health (GM R35, NIH-R01, OT2OD026682, U01 1U01HG010971, DK106766)
- National Institute of Standards and Technology
- National Institute on Aging (R01AG054712)
- National Institute of Mental Health (DP2 OD025824, DP2MH119424)
- National Human Genome Research Institute (R01HG010329, R01HG010485, R21HG010548, R21 1R21HG010548-01, HG009190, U01HG010971, U41HG007234, R01HG009190, F31HG011205, U01 1U01HG010971, R01HG011274, U01HG010961, U24HG010263, R01HG002385, U24HG011853, U24HG007234, U24HG006620, R01HG010169, R01HG002939, U41HG010972, U24HG010136)
- National Cancer Institute (R21CA240199, R21CA238758, U01CA253481, R01CA266339)
- National Institute of General Medical Sciences (GM134558, T32GM007445, R01GM117420, R01GM132600, R01GM123312, R01GM129263, F32GM134558, P20GM103546, R35GM139653, R01GM124041, R01GM074728)
- National Institute of Diabetes and Digestive and Kidney Diseases (NIH R01, R24DK106766)
- Division of Biological Infrastructure
- Division of Integrative Organismal Systems
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genome Rearrangement Algorithms
- Keywords
- human centromeres, pericentromeric repeats, centromeric repeats, telomere-to-telomere genome assembly, T2T-CHM13, repetitive DNA, structural rearrangement, centromere evolution, centromere position, epigenetic variation, chromosome segregation
- MeSH terms
- Centromere, Chromosome Mapping, Humans, Repetitive Sequences, Nucleic Acid, Genome, Human, Evolution, Molecular, Genomics, Epigenesis, Genetic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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