Year: 2022
Type: article
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.
Source: Science
Authors: 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, Julian K. Lucas, 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
Institutions: University of California, Berkeley, University of Washington, University of California San Diego, Stanford University, University of Connecticut, Sirius University of Science and Technology, Vavilov Institute of General Genetics, Moscow Polytechnic University, University of California, Davis, Johns Hopkins University, Stowers Institute for Medical Research, St Petersburg University, National Institutes of Health, National Human Genome Research Institute, University of California, Santa Cruz, University of Montana, Howard Hughes Medical Institute, University of Massachusetts Chan Medical School, Lomonosov Moscow State University, Chan Zuckerberg Biohub San Francisco, Lawrence Berkeley National Laboratory, QB3, Duke University, Duke Medical Center, University of Kansas, National Institute of Standards and Technology, Russian Academy of Sciences
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, Howard Hughes Medical Institute, Damon Runyon Cancer Research Foundation, Russian Foundation for Basic Research, Saint Petersburg State University, Russian Science Foundation, National Institutes of Health, National Institute of Standards and Technology, National Institute on Aging, National Institute of Mental Health, National Human Genome Research Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, Division of Biological Infrastructure, Division of Integrative Organismal Systems
Awards: G1596739982, Research PGR: Structural variant landscapes in tomato genomes and their role in natural variation, domestication and crop improvement, G2161041910, CAREER: Algorithms for single molecule sequence analysis, Development and Utilization of Splice-specific Antibodies, G2934504215, G2948735469, G3046833723, Ectopic centromere assembly in humans, Biochemistry, Cellular and Molecular Biology Program, Evolution of new regulatory networks via genetic arms races between KRAB zinc finger proteins and retrotransposons, Enabling Comparative Pangenomics, IMPROVING THROUGHPUT OF LONG READS WITH HIGH CONSENSUS BASE ACCURACY TO RESOLVE REPETITIVE DNAS, Genome Assembly and Analysis of the Bloom Forming Southern Ocean Salp, Salpa Thompsoni, Collaborative Research: Impact of a novel retrotransposon expansion on centromere function, G5135854252, Organization and Function of the Heterochromatin Holodomain and Subdomains, Epigenetic-Genetic Modulations in Aging and Alzheimer's Disease Neurons, G5520316217, The function of duplicated genes in human brain evolution and disease, Machine learning approaches for improved accuracy and speed in sequence annotation, Center for Human Reference Genome Diversity, G5991192147, Integrative genomic and epigenomic analysis of cancer using long read sequencing, G6607237905, GENCODE: comprehensive genome annotation for human and mouse, Nanopore based profiling of epigenetic state, Genetic and functional assessment of human-specific duplicated genes, G7009840428, The Role of Retroelements in Centromere Function, G778093658, Centromere Function and Dicentric Chromosome Stability, Comprehensive, flexible and FAIR Tools for the HuBMAP HIVE, RESEARCH-PGR: Living Fossils: Applying advances in single molecule sequencing to decode large and complex genomes of ancient plant lineages, Telomere-to-telomere assemblies of human genomes, Centromere Sequence, Variation, and Function, Biomolecular Structure and Dynamics, VISION: ValIdated Systematic IntegratiON of epigenomic data, The construction and utility of reference pan-genome graphs, G9000097457, Expanding the AnVIL (Analysis, Visualization, and Informatics Lab-space), Long-read sequence and assembly of segmental duplications, Dockstore: The Community Platform for Reproducible Biomedical Workflows and Applications, GENCODE: comprehensive gene annotation for human and mouse, Democratization of Data Analysis in Life Sciences Through Galaxy, Sequence resolution of complex human genome structural variation, Interplay Between Nuclear Organization and Function, Genomic Analysis of Centromere Assembly and Function, Mechanisms of Kinetochore Assembly, Development and Maintenance of RepeatMasker and RepeatModeler, The Human Pangenome Reference Consortium Coordination Center, Dfam: sustainable growth, curation support, and improved quality for mobile element annotation, Maintaining the integrity of a genome
OpenAlex ID: W4220937793