PT  - JOURNAL ARTICLE
AU  - Glennis A. Logsdon
AU  - Mitchell R. Vollger
AU  - PingHsun Hsieh
AU  - Yafei Mao
AU  - Mikhail A. Liskovykh
AU  - Sergey Koren
AU  - Sergey Nurk
AU  - Ludovica Mercuri
AU  - Philip C. Dishuck
AU  - Arang Rhie
AU  - Leonardo G. de Lima
AU  - David Porubsky
AU  - Andrey V. Bzikadze
AU  - Milinn Kremitzki
AU  - Tina A. Graves-Lindsay
AU  - Chirag Jain
AU  - Kendra Hoekzema
AU  - Shwetha C. Murali
AU  - Katherine M. Munson
AU  - Carl Baker
AU  - Melanie Sorensen
AU  - Alexandra M. Lewis
AU  - Urvashi Surti
AU  - Jennifer L. Gerton
AU  - Vladimir Larionov
AU  - Mario Ventura
AU  - Karen H. Miga
AU  - Adam M. Phillippy
AU  - Evan E. Eichler
TI  - The structure, function, and evolution of a complete human chromosome 8
AID  - 10.1101/2020.09.08.285395
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.09.08.285395
4099  - http://biorxiv.org/content/early/2020/09/08/2020.09.08.285395.short
4100  - http://biorxiv.org/content/early/2020/09/08/2020.09.08.285395.full
AB  - The complete assembly of each human chromosome is essential for understanding human biology and evolution. Using complementary long-read sequencing technologies, we complete the first linear assembly of a human autosome, chromosome 8. Our assembly resolves the sequence of five previously long-standing gaps, including a 2.08 Mbp centromeric α-satellite array, a 644 kbp defensin copy number polymorphism important for disease risk, and an 863 kbp 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 kbp hypomethylated region of diverse higher-order α-satellite enriched with CENP-A nucleosomes, consistent with the location of the kinetochore. Using a dual long-read sequencing approach, we complete the assembly of the orthologous chromosome 8 centromeric regions in chimpanzee, orangutan, and macaque for the first time to reconstruct its evolutionary history. Comparative and phylogenetic analyses show that the higher-order α-satellite structure evolved specifically in the great ape ancestor, and the centromeric region evolved with a layered symmetry, with more ancient higher-order repeats located at the periphery adjacent to monomeric α-satellites. We estimate that the mutation rate of centromeric satellite DNA is accelerated at least 2.2-fold, and this acceleration extends beyond the higher-order α-satellite into the flanking sequence.Competing Interest StatementThe authors have declared no competing interest.