High-Resolution Assembly of the Human Y Chromosome Identifies a Vast Landscape of Inverted Repeats Associated with Structural and Functional Genomic Features

High-Resolution Assembly of the Human Y Chromosome Identifies a Vast Landscape of Inverted Repeats Associated with Structural and Functional Genomic Features

Článek WoS

Recent advances in sequencing methods have led to major progress in the gapless assemblies of the human genome. However, until mid-2023, the complete sequence of the Y chromosome remained elusive. While only a small percentage of autosomal chromosomes were without complete sequences in the broadly used reference assembly of the human genome (GRCh38), around 50% of the chromosome Y DNA sequence was unknown. Using a sophisticated computational approach, we analyzed the presence of short inverted repeats in the current human reference genome (GRCh38) and in the Telomere-to-Telomere (T2T) assembly of chromosome Y. This analysis identified the location of the repeats in chromosome Y and highlighted their association with functionally annotated sequences. The comparison revealed notably more inverted repeats in the T2T assembly compared to GRCh38. These are located abundantly around exons and mobile elements, and, unexpectedly, also within gene annotations. The remarkable abundance of short inverted repeats around exons points to their importance in gene regulation, and their presence in regions associated with recombination suggests crucial roles in recombination processes. Interestingly, the most underestimated sequences in the T2T assembly are inverted repeats with a repeat length of 12-14, which are more than 20 times as frequent as those in the human reference genome GRCh38. These findings indicate that the number of short inverted repeats was significantly underestimated in the current human reference genome (GRCh38). These previously unidentified sites are of great bio-medicinal potential, as inverted repeats are precursors for the formation of cruciform DNA functional epitopes.

Recent advances in sequencing methods have led to major progress in the gapless assemblies of the human genome. However, until mid-2023, the complete sequence of the Y chromosome remained elusive. While only a small percentage of autosomal chromosomes were without complete sequences in the broadly used reference assembly of the human genome (GRCh38), around 50% of the chromosome Y DNA sequence was unknown. Using a sophisticated computational approach, we analyzed the presence of short inverted repeats in the current human reference genome (GRCh38) and in the Telomere-to-Telomere (T2T) assembly of chromosome Y. This analysis identified the location of the repeats in chromosome Y and highlighted their association with functionally annotated sequences. The comparison revealed notably more inverted repeats in the T2T assembly compared to GRCh38. These are located abundantly around exons and mobile elements, and, unexpectedly, also within gene annotations. The remarkable abundance of short inverted repeats around exons points to their importance in gene regulation, and their presence in regions associated with recombination suggests crucial roles in recombination processes. Interestingly, the most underestimated sequences in the T2T assembly are inverted repeats with a repeat length of 12-14, which are more than 20 times as frequent as those in the human reference genome GRCh38. These findings indicate that the number of short inverted repeats was significantly underestimated in the current human reference genome (GRCh38). These previously unidentified sites are of great bio-medicinal potential, as inverted repeats are precursors for the formation of cruciform DNA functional epitopes.

inverted repeats, human genome, chromosome Y, T2T, bioinformatics, non-B DNA structures

inverted repeats, human genome, chromosome Y, T2T, bioinformatics, non-B DNA structures

Dobrovolná, M.; Bowater, R.P.; Pečinka, P.; Brázda, V.; Bartas, M.

2026

20.10.2025

MDPI

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

26

20

Švýcarská konfederace

1

16

16

https://www.mdpi.com/1422-0067/26/20/10180

http://hdl.handle.net/11012/256358