The ‘weird’ male Y chromosome has finally been fully sequenced. Can we now understand how it works, and how it evolved?

Subject: Science and technology

Section: Biotechnology

Context:

The Y chromosome bears genes that determine maleness and make sperm.
It’s also small, carries few genes and is full of junk DNA that makes it horrendous to sequence.

Details:

The new “long-read” sequencing techniques have finally provided a reliable sequence from one end of the Y to the other.
The findings provide a solid base to explore:
- How genes for sex and sperm work,
- How the Y chromosome evolved, and
- Whether it will disappear in a few million years.

Determination of gender of fetus:

Females have a pair of X chromosomes, whereas males have a single X and a much smaller Y chromosome.
The Y chromosome is male-determining because it bears a gene called SRY, which directs the development of a ridge of cells into a testis in the embryo.
The embryonic testes make male hormones, and these hormones direct the development of male features in a baby boy.
Without a Y chromosome and a SRY gene, the same ridge of cells develops into an ovary in XX embryos. Female hormones then direct the development of female features in the baby girl.

A DNA junkyard:

The Y chromosome is smaller and bears few genes (only 27 compared to about 1,000 on the X).
Many Y genes (including the sperm genes RBMY and DAZ) are present in multiple copies, occurring in weird loops in which the sequence is inverted.
This “junk DNA” consists of highly repetitive sequences that derive from bits and pieces of old viruses, dead genes and very simple runs of a few bases repeated over and over.
- This last DNA class occupies big chunks of the Y that literally glow in the dark because it preferentially binds fluorescent dyes.

Why the Y is weird:

Around 150 million years ago X and Y were just a pair of ordinary chromosomes. As they still are in birds and platypuses.
Then SRY evolved on one of these two chromosomes, defining a new proto-Y.
- This proto-Y was forever confined to a testis and subject to mutations.
- The proto-Y degenerated fast, losing about 10 active genes per million years, reducing the number from its original 1,000 to just 27.
- A small “pseudoautosomal” region at one end retains its original form and is identical to its erstwhile partner, the X.
At this rate of degeneration the whole human Y would disappear in a few million years (as it already has in some rodents).

Sequencing Y was a tough task:

The first draft of the human genome was completed in 1999.
They’ve done this using short-read sequencing, which involves chopping the DNA into little bits of a hundred or so bases and reassembling them like a jigsaw.
The new technology has allowed sequencing of bases along individual long DNA molecules, producing long-reads of thousands of bases.
- These longer reads are easier to distinguish and can therefore be assembled more easily, handling the confusing repetitions and loops of the Y chromosome.
The Y is the last human chromosome to have been sequenced end-to-end, or T2T (telomere-to-telomere).

So what’s new on the Y?

A few new genes have been discovered, but these are extra copies of genes that were already known to exist in multiple copies.
We now know the structure of the centromere (a region of the chromosome that pulls copies apart when the cell divides), and have a complete readout of the complex mixture of repetitive sequences in the fluorescent end of the Y.

The sequencing of Y chromosome will help scientists in:

Looking for sequences that might control how SRY and the sperm genes are expressed, and to see whether genes that have X partners have retained the same functions or evolved new ones.
Examining the repeated sequences to determine where and how they originated, and why they were amplified.
Analyzing the Y chromosomes of men from different corners of the world to detect signs of degeneration, or recent evolution of function.