The structure, function, and evolution of a complete human chromosome 8
Glennis A. Logsdon,
Mitchell R. Vollger,
Mikhail A. Liskovykh,
Philip C. Dishuck,
Leonardo G. de Lima,
Andrey V. Bzikadze,
Tina A Graves-Lindsay,
Shwetha C. Murali,
Katherine M. Munson,
Alexandra M. Lewis,
Jennifer L. Gerton,
Karen H. Miga,
Adam M. Phillippy,
Evan E. Eichler
Posted 08 Sep 2020
bioRxiv DOI: 10.1101/2020.09.08.285395
Posted 08 Sep 2020
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 Statement The authors have declared no competing interest.
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