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

Glennis A. Logsdon, Mitchell R. Vollger, Ping Hsun Hsieh, Yafei Mao, Mikhail A. Liskovykh, Sergey Koren, Sergey Nurk, Ludovica Mercuri, Philip C. Dishuck, Arang Rhie, Leonardo G. de Lima, Tatiana Dvorkina, David Porubsky, William T. Harvey, Alla Mikheenko, Andrey V. Bzikadze, Milinn Kremitzki, Tina A. Graves-Lindsay, Chirag Jain, Kendra HoekzemaShwetha C. Murali, Katherine M. Munson, Carl Baker, Melanie Sorensen, Alexandra M. Lewis, Urvashi Surti, Jennifer L. Gerton, Vladimir Larionov, Mario Ventura, Karen H. Miga, Adam M. Phillippy, Evan E. Eichler

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


The complete assembly of each human chromosome is essential for understanding human biology and evolution1,2. 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.

Original languageEnglish
Pages (from-to)101-107
Number of pages7
Issue number7857
StatePublished - May 6 2021


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