May 2007
Tags: basics, chromosomes

The Y chromosome has had its share of fame in the last several years.

From jokes that the gene for not asking for directions when lost is on the Y chromosome, to claims the Y chromosome is shrinking and men are headed towards extinction, or that the Y chromosome may be the answer to your prayer of finding a long lost rich relative.

Get the real scoop here on the myths and truths about the Y chromosome.

What’s so special about the Y chromosome?
The Y chromosome gets its glory from the fact that you need a Y chromosome to be male — usually anyways. It turns out that that you only need a little morsel of the Y chromosome to develop into a male.

Chromosomes are the long spaghetti like structures that package up our genes.

We have 46 chromosomes in all of our body cells that are matched up into 23 pairs. The first 22 chromosomes, called ‘autosomes’, are the same in men and women. The 23rd pair of chromosomes is the sex chromosomes. If a person is female, she typically has two X chromosomes. If a person is male, he typically has one X and one Y chromosome.

For many years, it was thought that the Y chromosome was a genetic wasteland and its only use was in determining the male gender. However, more recent research has shown the Y chromosome has more to it than that.

While the Y chromosome may only have about 50 genes (5) compared to at least 1000 genes on its counterpart X chromosome, the Y chromosome harbours genes important in testis development, sperm production and reproduction.

So just how does the Y chromosome work in determining a person’s gender?
Up to 6 weeks into a human embryo’s development, the embryo has the potential to develop into either a male, or a female - it’s ‘bipotential’.

If a Y chromosome is present, the SRY gene (sex-determining region on Y, diagrammed below) is thought to produce a protein that switches on a cascade of events leading to the formation of a testis. This starts the embryo down the pathway to maleness.

By 12 weeks into the embryo’s development, if no Y chromosome is present an ovary is formed and the stage is set for the embryo to become female (5).

The Incredible Shrinking Y
As you can see from the picture to the right, the Y chromosome is much smaller than the X chromosome - quite interesting given that it is thought the X and Y chromosomes actually originated from an ordinary pair of autosomes.

It’s hypothesized that about 240-300 million years ago the first of a series of events occurred that would span millions of years and lead to one chromosome (the X) retaining most of the genes of the ancestral autosome. The other chromosome (the Y) lost many of its genes but gained a few new male specific genes (3,4)

Human Sex Chromosomes
The most popular theory is that the X and Y became different because of specific rearrangements of genetic material (“inversions”) that happened on the Y chromosome (6). Inversions are when a piece of genetic material breaks off from the chromosome, turns 180o and reattaches within the chromosome.

It is proposed that 4 inversions on the Y chromosome prevented it from being able to pair up and recombine with formerly matching sequences on the X chromosome(4).

The Y chromosome gradually accumulated genetic mutations because the Y chromosome could no longer completely line up with the X chromosome to swap information and repair its DNA sequence. Some mutations likely evolved into the ‘maleness factor’ SRY gene currently on the Y chromosome while other mutated genes would have been lost from the Y chromosome, turning it into the smaller chromosome that it is today.

Are males headed towards extinction?
The quick answer: probably not (men you can breathe a sign of relief!).

The longer explanation: Extinction of the Y chromosome was hypothesized because if the Y chromosome no longer had a matching chromosome to pair with and repair mistakes then mutated genes would continue to accumulate and be purged until there’s nothing left of the Y chromosome. However, it turns out that the Y chromosome has back-up copies of its important genes and the genes are protected within palindromes.

Palindrome Sequences
In the Y chromosome, palindrome sequences contain two ‘arms’ that are nearly identical in DNA sequence. The palindrome can bend at the middle to form a ‘hairpin’ structure, as pictured below. This brings each arm of the palindrome close together. If one palindrome arm has a mistake (DNA mutation), the other arm can correct it. The ability of the Y chromosome to repair itself is thought to protect the Y chromosome from extinction.

The Y chromosome: Your link to a long lost rich relative
The Y chromosome provides a way of tracing one’s paternal family history because the Y chromosome remains almost unchanged as it is passed down through males in a family. The Y remains unchanged because it doesn’t have a matching chromosome to swap parts with (no recombination occurs).

Markers (variable segments of DNA that can be tracked through the generations) within the male specific region on Y can be used to create a profile of a man’s Y chromosome. This profile can be run through private or public databases of other men’s Y chromosomes to find matching profiles. Matching profiles means the men are descendents of the same family line. Many commercial companies offer this service to the public. (This only works for men. To trace your family history through female relatives, mitochondrial DNA is used because it is inherited though the maternal line.).

So only a cheek swab and a couple hundred dollars may stand in the way of you and finding a long lost rich relative!

Genetic Conditions and the Y Chromosome
Deletions of part of the Y chromosome as well as translocations involving the SRY have been implicated in male infertility and the ‘sex-reversal’ condition.

 Male Infertility
Deletions or mutations of some male-specific genes on the Y chromosome cause infertility. In fact, it is thought that this may account for over 10% of cases of male infertility that is caused by no sperm production (azoospermia) (5). The DAZ genes and the USP9Y gene are examples of
genes found on the Y chromosome that are important in the normal production of sperm and when altered may cause infertility. For these reasons, genetic counselling may be helpful for some men with unexplained infertility.

Sex Reversal
Our knowledge that the SRY gene is key in determining maleness came from studies of the X and Y chromosomes in ‘sex-reversed’ individuals. Although typically it is only the pseudoautosomal regions (PAR) of the Y chromosome that recombine with the X chromosome in sperm production, rarely regions outside of the PAR can recombine. If the SRY region is involved, it can be moved to the X chromosome. If this sperm went on to fertilize an egg, the resulting individual would have an XX(+ SRY) genotype and be physically male. Alternatively if the sperm containing the Y chromosome that lost its SRY gene fertilized an egg, the resulting individual would be physically female but with an XY(-SRY) genotype.

The Y chromosome may be a little fella, but it packs a big punch. It is crucial in determining a person’s gender and important for successful reproduction. The Y has even devised clever ways of protecting the stability of its genes and can be used to trace a family line. The Y chromosome may have been underestimated in the past but it has proven itself to be a complex and valuable little chromosome.
 
References

1. http://www.hhmi.org/news/page6.html
2. MIT's Whitehead Institute website.
3. Cabe D. Book of Y: An unfinished story about the genesis of maleness. MIT’s Whitehead Institute of Biomedical Research. HHMI Bulletin 13(3): 20-25. 2000.
4. Willard H. Tales of the Y chromosome. Nature. 423: 810-812. 2003
5. Nussbaum RL et al. Thompson and Thompson Genetics in Medicine. 6th ed. 2004. Saunders.
6. Vogel G. Evolutionary Genetics: The why behind the Y chromosome. Science. 286(5441): 877-879. 1999.
7. Skaletsky H et al. The male specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature. 423: 825-837. 2003.
8. Rozen S et al. Abundant gene conversion between arms of palindromes in human and ape Y chromosome. Nature. 423: 873-876. 2003.