The structure, function and evolution of a complete human chromosome 8

The complete assembly of each human chromosome is essential for understanding human biology and evolution 1 , 2 . Here we use complementary long-read sequencing technologies to complete the linear assembly of human chromosome 8. Our assembly resolves the sequence of five previously long-standing gap...

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Published in:Nature (London) Vol. 593; no. 7857; pp. 101 - 107
Main Authors: Logsdon, Glennis A., Vollger, Mitchell R., Hsieh, PingHsun, Mao, Yafei, Liskovykh, Mikhail A., Koren, Sergey, Nurk, Sergey, Mercuri, Ludovica, Dishuck, Philip C., Rhie, Arang, de Lima, Leonardo G., Dvorkina, Tatiana, Porubsky, David, Harvey, William T., Mikheenko, Alla, Bzikadze, Andrey V., Kremitzki, Milinn, Graves-Lindsay, Tina A., Jain, Chirag, Hoekzema, Kendra, Murali, Shwetha C., Munson, Katherine M., Baker, Carl, Sorensen, Melanie, Lewis, Alexandra M., Surti, Urvashi, Gerton, Jennifer L., Larionov, Vladimir, Ventura, Mario, Miga, Karen H., Phillippy, Adam M., Eichler, Evan E.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 06.05.2021
Nature Publishing Group
Subjects:
13/106
14/19
14/32
14/63
38/1
45/15
45/22
45/23
45/29
45/90
631/181/2474
631/208/212
631/208/212/2304
631/337/103/90
Accuracy
Animals
Arrays
Artificial chromosomes
Assembly
Cell Line
Centromere - chemistry
Centromere - genetics
Centromere - metabolism
Centromere protein A
Chromosome 8
Chromosomes
Chromosomes, Human, Pair 8 - chemistry
Chromosomes, Human, Pair 8 - genetics
Chromosomes, Human, Pair 8 - physiology
Copy number
Deoxyribonucleic acid
Diploids
DNA
DNA Methylation
DNA, Satellite - genetics
Epigenesis, Genetic
Evolution
Evolution, Molecular
Female
Gene polymorphism
Genes
Genomes
Genomics
Haplotypes
Health risks
Humanities and Social Sciences
Humans
Macaca mulatta - genetics
Male
Minisatellite Repeats - genetics
multidisciplinary
Mutation
Mutation rates
Nucleosomes
Nucleotide sequence
Pan troglodytes - genetics
Phylogeny
Polymorphism
Pongo abelii - genetics
Satellite DNA
Satellites
Science
Science (multidisciplinary)
Structure-function relationships
Telomere - chemistry
Telomere - genetics
Telomere - metabolism
ISSN:0028-0836, 1476-4687, 1476-4687
Online Access:Get full text
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Summary:The complete assembly of each human chromosome is essential for understanding human biology and evolution 1 , 2 . Here we use complementary long-read sequencing technologies to complete the linear assembly of human chromosome 8. Our assembly resolves the sequence of five previously long-standing gaps, including a 2.08-Mb centromeric α-satellite array, a 644-kb copy number polymorphism in the β-defensin gene cluster that is important for disease risk, and an 863-kb variable number tandem repeat at chromosome 8q21.2 that can function as a neocentromere. We show that the centromeric α-satellite array is generally methylated except for a 73-kb hypomethylated region of diverse higher-order α-satellites enriched with CENP-A nucleosomes, consistent with the location of the kinetochore. In addition, we confirm the overall organization and methylation pattern of the centromere in a diploid human genome. Using a dual long-read sequencing approach, we complete high-quality draft assemblies of the orthologous centromere from chromosome 8 in chimpanzee, orangutan and macaque to reconstruct its evolutionary history. Comparative and phylogenetic analyses show that the higher-order α-satellite structure evolved in the great ape ancestor with a layered symmetry, in which more ancient higher-order repeats locate peripherally to monomeric α-satellites. We estimate that the mutation rate of centromeric satellite DNA is accelerated by more than 2.2-fold compared to the unique portions of the genome, and this acceleration extends into the flanking sequence. The complete assembly of human chromosome 8 resolves previous gaps and reveals hidden complex forms of genetic variation, enabling functional and evolutionary characterization of primate centromeres.
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ISSN:0028-0836
1476-4687
1476-4687
DOI:10.1038/s41586-021-03420-7