General Studies Paper 3

Introduction

• 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.

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.

A DNA junkyard

• 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.

Y chromosome is weird!

• 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).

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.

Conclusion

• The most important outcome is how useful the findings will be for scientists all over the world. It’s a new era for the poor old Y.