The variation and evolution of complete human centromeres

Abstract Human centromeres have been traditionally very difficult to sequence and assemble owing to their repetitive nature and large size 1 . 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 regions 2,3 . Here, using long-read sequencing, we completely sequenced and assembled all centromeres from a second human genome and compared it to the finished reference genome 4,5 . 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…