Rapid and ongoing evolution of repetitive sequence structures in human centromeres

Area of Science:

• Genomics
• Human Genetics
• Evolutionary Biology

Background:

• Centromere sequences, characterized by long, nested higher-order repeats, are difficult to sequence, limiting our understanding of human population variation.
• Previous studies have been hampered by the repetitive nature of these regions, hindering comprehensive analysis of structural diversity.

Purpose of the Study:

• To investigate sequence variation and structural diversity within human centromeres across diverse populations.
• To characterize the evolution of centromeric arrays and identify novel variants using advanced sequencing technologies.

Main Methods:

• Analysis of long-read sequencing data from 36 individuals from diverse human populations, including a Han Chinese trio and Japanese individuals.
• Focus on chromosomes 11, 17, and X to examine higher-order repeat structures and sequence variants.

Main Results:

• Substantial structural diversity was identified in human centromeric arrays, with numerous previously unknown variant higher-order repeats.
• Rapid, haplotype-specific evolution of centromeric arrays was observed, contrasting with largely conserved single-nucleotide variants.
• A shared evolutionary pattern was detected between human and chimpanzee centromeric variants.

Conclusions:

• Long-read sequencing enables detailed characterization of complex centromeric regions, revealing significant structural variation.
• Human centromeric arrays exhibit rapid, population-specific evolution, driven by changes in higher-order repeats.
• The findings provide a foundation for future studies on sequence evolution in human and primate centromeres.