Puzzle Solved: Complete Y chromosome sequence finally assembled

 

Source: bionity.com

In August 2023, a major breakthrough marked the completion of the human Y chromosome's genetic sequence, making it the last human chromosome to be fully sequenced. A collaboration of researchers known as the Telomere-2-Telomere Consortium (T2T) utilized new DNA sequencing technologies and existing knowledge gleaned from generating the first gapless sequences for the other 23 human chromosomes. 

The Y chromosome, primarily known for its role in sexual development, is found in individuals who are assigned males at birth. Despite its prevalence, for many years, more than half of the Y chromosome’s DNA sequence remained unknown. 

The Y chromosome long arm contains highly repetitive DNA regions called satellite DNA, which exist in high copy numbers at multiple genomic locations that make it challenging to accurately sequence. This led to the speculation that the composition of the missing sequence was chaotic, but their findings have been quite the contrary, much to the surprise of the researchers. Adam Phillipy, one of the leaders of T2T Consortium, said that “nearly half of the chromosome is made of alternating blocks of two specific repeating satellite DNA sequences forming a beautiful, quilt-like pattern”.

Throughout the 20th century, studies of the Y chromosome were tainted by eugenics and led to stigmatizing beliefs of the general public. Individuals with two Y chromosomes were labeled as "subnormal" due to Double Y Syndrome or Jacobs syndrome, which affects about 1 in 1,000 male individuals. Moreover, the generalization of genetic basis to aggression and violence, particularly rooted in the Y chromosome, added to the stigmatization.

Hence, the complete sequencing of the Y chromosome not only brings us one step further away from the misconstructed understanding of the elusive chromosome but also propels us toward clinical advancements in reproduction and fertility.

Medically relevant regions were also discovered in the complete sequence of the Y chromosome. One of which is the azoospermia factor region, a stretch of DNA containing a set of inverted repeats or “palindromes”  known to be involved in sperm production. These loops accidentally get cut off and create deletions in the azoospermia factor region, which is known to disrupt sperm production. Studying these palindromes in the Y chromosome allows a deeper understanding of sperm and production and helps in designing better diagnostics on fertility.

In addition to the completion of the Y chromosome sequence, the T2T Consortium also reported the sequence of 43 diverse human Y chromosomes, which revealed an extensive diversity in size and structure. Half of the male-specific euchromatic region contained large inversions at a recurrence rate more than twice compared with all other chromosomes. The completion of the Y chromosome sequence is a significant scientific milestone that unraveled our deep misconceptions about human biology and opened new horizons in the study of genomic medicine.