Logsdon, Glennis A. and Rozanski, Allison N. and Ryabov, Fedor and Potapova, Tamara and Shepelev, Valery A. and Catacchio, Claudia R. and Porubsky, David and Mao, Yafei and Yoo, DongAhn and Rautiainen, Mikko and Koren, Sergey and Nurk, Sergey and Lucas, Julian K. and Hoekzema, Kendra and Munson, Katherine M. and Gerton, Jennifer L. and Phillippy, Adam M. and Ventura, Mario and Alexandrov, Ivan A. and Eichler, Evan E. (2024) The variation and evolution of complete human centromeres. Nature. ISSN 0028-0836
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Abstract
Human centromeres have been traditionally very difficult to sequence and assemble owing to their repetitive nature and large size1. As a result, patterns of human centromeric variation and models for their evolution and function remain incomplete, despite centromeres being among the most rapidly mutating regions2,3. Here, using long-read sequencing, we completely sequenced and assembled all centromeres from a second human genome and compared it to the finished reference genome4,5. We find that the two sets of centromeres show at least a 4.1-fold increase in single-nucleotide variation when compared with their unique flanks and vary up to 3-fold in size. Moreover, we find that 45.8% of centromeric sequence cannot be reliably aligned using standard methods owing to the emergence of new α-satellite higher-order repeats (HORs). DNA methylation and CENP-A chromatin immunoprecipitation experiments show that 26% of the centromeres differ in their kinetochore position by >500 kb. To understand evolutionary change, we selected six chromosomes and sequenced and assembled 31 orthologous centromeres from the common chimpanzee, orangutan and macaque genomes. Comparative analyses reveal a nearly complete turnover of α-satellite HORs, with characteristic idiosyncratic changes in α-satellite HORs for each species. Phylogenetic reconstruction of human haplotypes supports limited to no recombination between the short (p) and long (q) arms across centromeres and reveals that novel α-satellite HORs share a monophyletic origin, providing a strategy to estimate the rate of saltatory amplification and mutation of human centromeric DNA.
Item Type: | Article |
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Subjects: | Euro Archives > Multidisciplinary |
Depositing User: | Managing Editor |
Date Deposited: | 08 Apr 2024 08:09 |
Last Modified: | 08 Apr 2024 08:09 |
URI: | http://publish7promo.com/id/eprint/4630 |