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

## TL;DR

A detailed analysis of the human Y chromosome reveals a large number of previously unknown inverted repeats, which may play important roles in gene regulation and DNA structure.

## Contribution

The study identifies a vast number of short inverted repeats in the newly assembled Y chromosome, which were significantly underestimated in previous genome references.

## Key findings

- The T2T assembly of the Y chromosome contains significantly more short inverted repeats than the GRCh38 reference genome.
- These repeats are found abundantly around exons, mobile elements, and within gene annotations, suggesting roles in gene regulation and recombination.
- Inverted repeats of 12–14 base pairs are the most underestimated and over 20 times more frequent in the T2T assembly compared to GRCh38.

## Abstract

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.