The Y chromosome is a unending supply of fascination (notably to males) as a result of it bears genes that decide maleness and make sperm. It’s additionally small and significantly bizarre; it carries few genes and is stuffed with junk DNA that makes it horrendous to sequence.
However, new “long-read” sequencing methods have finally offered a dependable sequence from one finish of the Y to the opposite. The paper describing this Herculean effort has been revealed in Nature.
The findings present a stable base to discover how genes for intercourse and sperm work, how the Y chromosome advanced, and whether or not – as predicted – it will disappear in just a few million years.
Making child boys
We have recognized for about 60 years that specialised chromosomes decide beginning intercourse in people and different mammals. Females have a pair of X chromosomes, whereas males have a single X and a a lot smaller Y chromosome.
The Y chromosome is male-determining as a result of it bears a gene referred to as SRY, which directs the event of a ridge of cells right into a testis within the embryo. The embryonic testes make male hormones, and these hormones direct the event of male options in a child boy.
Without a Y chromosome and a SRY gene, the identical ridge of cells develops into an ovary in XX embryos. Female hormones then direct the event of feminine options within the child woman.
A DNA junkyard
The Y chromosome may be very totally different from X and the 22 different chromosomes of the human genome. It is smaller and bears few genes (solely 27 in comparison with about 1,000 on the X).
These embody SRY, just a few genes required to make sperm, and a number of genes that appear to be important for all times – lots of which have companions on the X. Many Y genes (together with the sperm genes RBMY and DAZ) are current in a number of copies. Some happen in bizarre loops by which the sequence is inverted and genetic accidents that duplicate or delete genes are frequent.
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The Y additionally has quite a lot of DNA sequences that don’t appear to contribute to traits. This “junk DNA” is comprised of extremely repetitive sequences that derive from bits and items of outdated viruses, lifeless genes and quite simple runs of some bases repeated over and over.
This final DNA class occupies massive chunks of the Y that actually glow at midnight; you may see it down the microscope as a result of it preferentially binds fluorescent dyes.
Why the Y is bizarre
Why is the Y like this? Blame evolution.
We have quite a lot of proof that 150 million years in the past the X and Y have been only a pair of extraordinary chromosomes (they nonetheless are in birds and platypuses). There have been two copies – one from every guardian – as there are for all chromosomes.
Then SRY advanced (from an historic gene with one other perform) on considered one of these two chromosomes, defining a brand new proto-Y. This proto-Y was without end confined to a testis, by definition, and topic to a barrage of mutations on account of quite a lot of cell division and little restore.
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The proto-Y degenerated quick, shedding about 10 lively genes per million years, lowering the quantity from its authentic 1,000 to only 27. A small “pseudoautosomal” area at one finish retains its authentic type and is similar to its erstwhile associate, the X.
There has been nice debate about whether or not this degradation continues, as a result of at this price the entire human Y would disappear in just a few million years (as it already has in some rodents).
Sequencing Y was a nightmare
The first draft of the human genome was accomplished in 1999. Since then, scientists have managed to sequence all of the extraordinary chromosomes, together with the X, with just some gaps.
They’ve achieved this utilizing short-read sequencing, which includes chopping the DNA into little bits of 100 or so bases and reassembling them like a jigsaw.
But it’s solely just lately that new expertise has allowed sequencing of bases alongside particular person lengthy DNA molecules, producing long-reads of hundreds of bases. These longer reads are simpler to tell apart and can subsequently be assembled extra simply, dealing with the complicated repetitions and loops of the Y chromosome.
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The Y is the final human chromosome to have been sequenced end-to-end, or T2T (telomere-to-telomere). Even with long-read expertise, assembling the DNA bits was usually ambiguous, and researchers needed to make a number of makes an attempt at troublesome areas – notably the extremely repetitive area.
So what’s new on the Y?
Spoiler alert – the Y seems to be simply as bizarre as we anticipated from a long time of gene mapping and the earlier sequencing.
Just a few new genes have been found, however these are additional copies of genes that have been already recognized to exist in a number of copies. The border of the pseudoautosomal area (which is shared with the X) has been pushed a bit additional towards the tip of the Y chromosome.
We now know the construction of the centromere (a area of the chromosome that pulls copies aside when the cell divides), and have an entire readout of the complicated combination of repetitive sequences within the fluorescent finish of the Y.
But maybe a very powerful end result is how helpful the findings can be for scientists all around the world.
Some teams will now study the main points of Y genes. They will search for sequences that may management how SRY and the sperm genes are expressed, and to see whether or not genes which have X companions have retained the identical capabilities or advanced new ones.
Others will intently study the repeated sequences to find out the place and how they originated, and why they have been amplified. Many teams may also analyse the Y chromosomes of males from totally different corners of the world to detect indicators of degeneration, or current evolution of perform.
It’s a brand new period for the poor outdated Y.
