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

Nature. 2021 May;593(7857):101-107. doi: 10.1038/s41586-021-03420-7. Epub 2021 Apr 7.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Centromere / chemistry
  • Centromere / genetics
  • Centromere / metabolism
  • Chromosomes, Human, Pair 8 / chemistry*
  • Chromosomes, Human, Pair 8 / genetics*
  • Chromosomes, Human, Pair 8 / physiology
  • DNA Methylation
  • DNA, Satellite / genetics
  • Epigenesis, Genetic
  • Evolution, Molecular*
  • Female
  • Humans
  • Macaca mulatta / genetics
  • Male
  • Minisatellite Repeats / genetics
  • Pan troglodytes / genetics
  • Phylogeny
  • Pongo abelii / genetics
  • Telomere / chemistry
  • Telomere / genetics
  • Telomere / metabolism


  • DNA, Satellite