The Y Chromosome

The nuclei of human cells contain 22 autosomes and 2 sex chromosomes. In females, the sex chromosomes are the 2 X chromosomes. Males have one X chromosome and one Y chromosome.  A human karyotype is shown with the sex chromosomes in the lower right corner.
 
 
 
 
 
 

1.	3.	4.	1.  The human X and Y chromosome, showing structure and relative size. 2.  The human X and Y chromosome stained with fluorescent dye and viewed under a fluorescense microscope. 3.  An idiogram of the human X and Y chromosome, showing banding patterns and relative size. 4.  An idiogram of the human Y chromosome showing general structure, position of pseudoautosomal regions, and the locus of the SRY gene.
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The Pseudoautosomal Region

The importance of the pseudoautosomal regions is that, because of the homology between the pseudoautosomal regions, the X and Y chromosomes can synapse during meiosis.  As a result, the sex chromosomes will segregate during anaphase in the same orderly way as homologous pairs of autosomes do. What would happen if the X and Y chromosome did not share regions of homology and therefore could not synapse?  This image, courtesy of C. Tease of Harvard University, shows synapsis of the X and Y chromosomes of a mouse during prophase of meiosis I.

How does the presence of pseudoautosomal regions on the Y chromosome suggest a hypothesis about the aberrant phenotype in Turner's Syndrome ?
 
 
 

The SRY locus

As you know already, the X-Y system of sex determination is found in many kinds of organisms besides mammals. The fruit fly, Drosophila, uses such a system as do a number of plants that have separate sexes (e.g., Cannabis sativa, the source of hemp and marijuana). A similar system is found in birds and moths, but here the male has two of the same chromosome (designated ZZ), whereas the female has "heterogametic" chromosomes (designated Z and W).

Also as you know by now, the female sexual phenotype is the default developmental pathway.  In order to get a male 2 things must happen:

1.    the female developmental pathway must be "turned off".
2.    the male developmental pathway must be "turned on".

The key player in this latter group is SRY (for sex-determining regionY) .  In older studies it is referred to as TDF (testis determining factor), but they are the same gene.  SRY is a 35 kb (kilobase) gene located on the short (p) arm of the Y just outside the pseudoautosomal region. It is the master switch that triggers the events that converts the embryo into a male. Without this gene (and the Y chromosome which it),  a female develops.  On the other hand, with the Y chromosome and the SRY gene, a male develops even if there are 2 X chromosomes (XXY) or 3 X chromosomes (XXXY).
 
 

Other holandric genes  on the Y chromosome

Ten years ago the human Y chromosome was thought to be a small genetic wasteland with only one important gene (SRY) which determined sexual development.  However, research at the Whitehead Institute for Biomedical Research in 1997 began to reverse this unflattering picture of the Y.  These results are not only generating a new respect for the Y chromosome but also could lead to novel diagnostic techniques for thousands of infertile men. The results also have profound implications for understanding the genetic differences between men and women and the genetic underpinnings of chromosomal disorders such as Turner syndrome.

In the October 24, 1997 issue of Science, Page and Lahn report that a systematic search of the Y chromosome yielded 12 novel genes in the NRY region of the Y  (the non-recombining region region of the Y is not homologous to any region on the X chromosome, so there is no recombination or exchange genetic material between the two).  Along with eight previously identified genes, the 12 novel genes compose a substantial, nearly comprehensive catalog of genes found in the NRY, which constitutes 95 percent of the Y chromosome.

The 12 new genes, and six of the eight previously discovered Y chromosome genes, can be sorted into two categories: 

• Five were homologous to genes found on the X chromosome and occur in single copy.  They perform housekeeping functions and are expressed in many organs.  Some of these genes may be involved in Turner’s Syndrome.

• The other seven genes are found only on the Y.  They occur in multiple copies on the NRY.  They are probably are responsible for enhancing male fertility, and are specifically expressed only in the testes.

"These results show that the Y chromosome is functionally coherent; it has a short list of missions to which it is dedicated. By contrast, other human chromosomes contain motley assortments of genes with no theme or unifying purpose apparent. The human Y chromosome is a striking exception” says Professor Page.
 
 
 
 
 
 
 

Mutation and Translocation of the SRY locus

 
 

An interesting example of the expression of SRY is the two mice in this photograph.  Both have an XX karyotype and thus should be female, but they have the male sexual phenotype instead. This is because they were engineered to have the SRY gene!  Mouse ova were fertilized in vitro, and XX zygotes were injected with DNA carrying the SRY gene.  These zygotes were implanted in a surrogate mother.  These 2 pseudo-males were the result.  Although these XX mice have testes, male sex hormones, and normal male mating behavior, they are sterile. pseudo-males in humans:  occasionally a piece of Y chromosome carrying the SRY gene may get translocated onto an X chromosome.  An embryo which inherited this X chromosome would have an XX karyotype like the mice above, but has testicular tissue and a masculinized phenotype. pseudo-females in humans:   occasionally the SRY gene on a Y chromosome may be damaged, resulting in a defective allele.  Since this allele of SRY is non-functional a zygote would have an XY karyotype, but a female sexual phenotype. In the Olympics, all female athletes are tested to be sure they do not have the SRY gene.  This screens out any pseudo-females who might have an advantage because of higher testosterone levels.

Saint Joan of Arc:  Joan was a peasant, born in 1412 during the Hundred Years War between France and England. At around the age of 13, she began having visions and hearing voices. Finally they instructed her to see the Daupin crowned King of France at Rheims. In 1429 she became commander of a French army, and defeated the English at Orleans. This opened the way to Rheims and the Dauphin was coronated there on July 17. The following year she was captured during a battle at Compiegne. The English tried her as a heretic, and burned her at the stake on May 30, 1431.  Joan was possessed of great physical strength, wore men's clothes, and there are reports that during her imprisonment she was never observed to menstruate. This has given rise to the hypothesis that she was a pseudo-female ..... although the evidence is circumstantial and virulently criticized by some.

 

From the "Journal of Irreproducible Results"