An international team of scientists led by researchers from the National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA, together with colleagues from the University of California Santa Cruz, Santa Cruz, CA, USA, the University of Connecticut, Storrs, CT, USA, Johns Hopkins University, Baltimore, MD, USA, have finally completed the task of sequencing the entire human Y chromosome from end to end or T2T (Telomere-to-Telomere). This completes the entire human genome now sequenced T2T.
Unsurprisingly, they found that most of the DNA was non-functional junk, containing the remnants of ancient retroviruses and duplicated genes that had then mutated.
The X and Y chromosomes, or sex chromosomes, are how gender is determined in humans and other mammals. Females have two copies of the X chromosome while males have one of each. Males inherit their Y chromosome from their father.
The significance of the research, and how it informs our understanding of the evolution of the Y chromosome from one of the two X chromosomes that females carry is the subject of an article in The Conversation by Professor Jenny Graves Jenny Graves, La Trobe University, Australia. Her article is reprinted here under a Creative Commons Licence, reformatted for stylistic consistency:
The ‘weird’ male Y chromosome has finally been fully sequenced. Can we now understand how it works, and how it evolved?
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Jenny Graves, La Trobe University
The Y chromosome is a never-ending source of fascination (particularly to men) because it bears genes that determine maleness and make sperm. It’s also small and seriously weird; it carries few genes and is full of junk DNA that makes it horrendous to sequence.
However, new “long-read” sequencing techniques have finally provided a reliable sequence from one end of the Y to the other. The paper describing this Herculean effort has been published in Nature.
The findings provide a solid base to explore how genes for sex and sperm work, how the Y chromosome evolved, and whether – as predicted – it will disappear in a few million years.
Making baby boys
We have known for about 60 years that specialised chromosomes determine birth sex in humans and other mammals. 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.
Our 20,000-odd genes are stretches of DNA sequenced with four basic molecular modules, or ‘bases’. These code for the thousands of proteins that make up our bodies.
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The Y chromosome is very different from X and the 22 other chromosomes of the human genome. It is smaller and bears few genes (only 27 compared to about 1,000 on the X).
These include SRY, a few genes required to make sperm, and several genes that seem to be critical for life – many of which have partners on the X. Many Y genes (including the sperm genes RBMY and DAZ) are present in multiple copies. Some occur in weird loops in which the sequence is inverted and genetic accidents that duplicate or delete genes are common.
The Y also has a lot of DNA sequences that don’t seem to contribute to traits. This “junk DNA” is comprised 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; you can see it down the microscope because it preferentially binds fluorescent dyes.
Why the Y is weird
Why is the Y like this? Blame evolution.
We have a lot of evidence that 150 million years ago the X and Y were just a pair of ordinary chromosomes (they still are in birds and platypuses). There were two copies – one from each parent – as there are for all chromosomes.
Then SRY evolved (from an ancient gene with another function) on one of these two chromosomes, defining a new proto-Y. This proto-Y was forever confined to a testis, by definition, and subject to a barrage of mutations as a result of a lot of cell division and little repair.
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.
There has been great debate about whether this degradation continues, because at this rate the whole human Y would disappear in a few million years (as it already has in some rodents).
Sequencing Y was a nightmare
The first draft of the human genome was completed in 1999. Since then, scientists have managed to sequence all the ordinary chromosomes, including the X, with just a few gaps.
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.
But it’s only recently that 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). Even with long-read technology, assembling the DNA bits was often ambiguous, and researchers had to make several attempts at difficult regions – particularly the highly repetitive region.
So what’s new on the Y?
Spoiler alert – the Y turns out to be just as weird as we expected from decades of gene mapping and the previous sequencing.
A few new genes have been discovered, but these are extra copies of genes that were already known to exist in multiple copies. The border of the pseudoautosomal region (which is shared with the X) has been pushed a bit further toward the tip of the Y chromosome.
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.
But perhaps the most important outcome is how useful the findings will be for scientists all over the world.
Some groups will now examine the details of Y genes. They will look 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.
Others will closely examine the repeated sequences to determine where and how they originated, and why they were amplified. Many groups will also analyse the Y chromosomes of men from different corners of the world to detect signs of degeneration, or recent evolution of function.
It’s a new era for the poor old Y.
Jenny Graves, Distinguished Professor of Genetics and Vice Chancellor's Fellow, La Trobe University
This article is republished from The Conversation under a Creative Commons license. Read the original article.
AbstractPretty much what we've come to expect from biomedical research, when scientists dig beneath the surface and find out the details: no evidence of intelligence or the involvement of supernatural deities and every evidence of mindless, utilitarian design, just as the Theory of Evolution predicts. There is the usual mix of needless complexity and prolific waste that charcterises evolved systems and distinguishes them from intelligently designed system.
The human Y chromosome has been notoriously difficult to sequence and assemble because of its complex repeat structure that includes long palindromes, tandem repeats and segmental duplications1,2,3. As a result, more than half of the Y chromosome is missing from the GRCh38 reference sequence and it remains the last human chromosome to be finished4,5. Here, the Telomere-to-Telomere (T2T) consortium presents the complete 62,460,029-base-pair sequence of a human Y chromosome from the HG002 genome (T2T-Y) that corrects multiple errors in GRCh38-Y and adds over 30 million base pairs of sequence to the reference, showing the complete ampliconic structures of gene families TSPY, DAZ and RBMY; 41 additional protein-coding genes, mostly from the TSPY family; and an alternating pattern of human satellite 1 and 3 blocks in the heterochromatic Yq12 region. We have combined T2T-Y with a previous assembly of the CHM13 genome4 and mapped available population variation, clinical variants and functional genomics data to produce a complete and comprehensive reference sequence for all 24 human chromosomes.
Rhie, A., Nurk, S., Cechova, M. et al.
The complete sequence of a human Y chromosome.
Nature (2023). https://doi.org/10.1038/s41586-023-06457-y
© 2023 Springer Nature Ltd.
Reprinted under the terms of s60 of the Copyright, Designs and Patents Act 1988.
And, of course, despite creationist's claims otherwise, the scientists express no doubt at all that the system they are examining is the product of evolution.
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