Y chromosome

The Y chromosome is one of the two sex-determining chromosomes in humans and most other mammals, the other being the X chromosome. As part of the XY sex-determination system, it contains the genes that cause testis development, thus determining maleness.

Function

Each individual normally has one pair of sex chromosomes in each cell. As a general rule, the Y chromosome is present in males, who have one X and one Y chromosome, while females have two X chromosomes. However there are exceptions where this is not the case, for details see Intersex. Many of the genes on the Y chromosome are involved in male sexual determination and development; two genes of particular importance for sex determination are the SRY gene (in humans and other primates) and UBE1 (in most other mammals).

Origins and evolution

Many ectothermic vertebrates have no sex chromosomes. If they have different sexes, sex is determined environmentally rather than genetically. For some of them, especially reptiles, sex depends on the incubation temperature, others are hermaphroditic.

The X and Y chromosome diverged around 300 millions years ago ^* when some reptile, which was a distant ancestor of all mammals, developed a gene which makes all its owners to be males. The chromosome with this gene became the Y chromosome, and a similar chromosome without it became the X chromosome. So initially, X and Y chromosomes were nearly identical. Over time, genes which were beneficial for males and harmful or had no effect for females either moved to the Y chromosome or emerged independently developed on it.

However, recombination between the X and Y chromosome was harmful because it provided males without needed male genes or females with unneeded male genes. As a result, male genes assembled around the sex determining gene in order to make this less probable. Eventually, the Y chromosome changed in such a way that the areas around the sex determining gene lost any ability to recombine with X chromosome.

With time, the larger and larger areas lost ability to recombine with the X chromosome. However, without recombination it is hard for chromosomes to get rid of harmful mutations. Therefore, harmful mutations increasingly damaged male genes until some stopped functioning and became genetic junk, eventually being removed from the Y chromosome.

As a result of this process, for humans, 95% of the Y chromosome is unable to recombine, and Y chromosome contains only 78 working genes ^* versus about 1000 genes for X chromosome. For some other animals, the degradation of Y chromosome is even more severe. For example, the Y chromosome in kangaroos contains only the SRY gene.

Gene conversion

In 2003, researchers from the Washington University discovered another process which may slow down the process of degradation ^*. They found that human Y chromosome is able to "recombine" with itself, using palindrome base pair sequences. Such a "recombination" is called gene conversion or "recombinational loss of heterozygosity" RecLOH.

In the case of the Y chromosomes, the palindromes are not junk DNA; these strings of bases contain functioning genes important for male fertility. Most of the sequence pairs are greater than 99.97 % identical. The extensive use of gene conversion may play a role in the ability of the Y chromosome to edit out genetic mistakes and maintain the integrity of the relatively few genes it carries.

Findings were confirmed by comparing similar regions of the Y chromosome in humans to the Y chromosomes of chimpanzees, bonobos and gorillas. The comparison demonstrated that the same phenomenon of gene conversion appeared to be at work more than 5 million years ago, when humans and the non-human primates diverged from each other.

This recombination phenomenon RecLOH is also observed in Genetic Genealogy when multicopy Y-STR markers located at adjacent palindromic arms change from different repeat counts to twin alleles of equal length. Often 2, 3 or more Y-STR markers are involved in the same recombinational event and change to twin alleles at once.

Future evolution

After only an SRY (or other sex-determining) gene remains from the whole Y chromosome, there are the following possibilities:

The gene is connected to X chromosome or some autosome, making it the new Y chromosome. The whole process starts again. This has happened with two species of mole vole (Ellobius tancrei and E. lutescens). In one species, both sexes have unpaired X chromosomes; in the other, both females and males have XX.
Part of some autosome is connected to both the X and Y chromosomes. This happened with one species of Drosophila.

Human Y chromosome

In humans, the Y chromosome spans 58 million base pairs (the building blocks of DNA) and represents approximately 0.38% of the total DNA in a human cell. The human Y chromosome contains 78 genes, which code for only 23 distinct proteins. This relationship is typical in that most species' Y chromosomes contain the fewest genes of any of the chromosomes.

Because the Y chromosome changes relatively slowly over time and is only passed along the direct male line, it may be used to trace paternal lineage. It is the cause of the fewest number of known genetic diseases in humans (44 in total).

The human Y chromosome is unable to recombine with the X chromosome, except for small pieces on the ends (which comprise about 5% of the chromosome's length). About 56, or 72%, of the Y chromosome genes are in this area; as a result, these genes are common between both sex chromosomes.

Genes

AMELY (amelogenin,Y-chromosomal)
ANT3Y (adenine nucleotide translocator-3 on the Y)
ASMTY (which stands for acetylserotonin methyltransferase)
AZF1 (azoospermia factor 1)
AZF2 (azoospermia factor 2)
BPY2 (basic protein on the Y chromosome)
CSF2RY (granulocyte-macrophage colony-stimulating factor receptor, alpha subunit on the Y chromosome)
DAZ (deleted in azoospermia)
IL3RAY (interleukin-3 receptor)
PRKY (protein kinase, Y-linked)
RBM1 (RNA binding motif protein, Y chromosome, family 1, member A1)
RBM2 (RNA binding motif protein 2)
SRY (sex-determining region)
TDF (testis determining factor)
TSPY (testis-specific protein)
UTY (ubiquitously transcribed TPR gene on Y chromosome)
ZFY (zinc finger protein)

Chromosome-linked diseases

No vital genes reside only on the Y chromosome, since 50% of humans do not have Y chromosomes. The only well-defined human disease linked to a defect on the Y chromosome is defective testicular development (due to deletion or deleterious mutation of SRY. This results in sex reversal, so that a person with an XY karyotype has a female phenotype (i.e., is born a female). The lack of the second X results in infertility.

However, it is possible for an abnormal number (aneuploidy) of Y chromosomes to result in problems.

47,XYY syndrome is caused by the presence of a single extra copy of the Y chromosome in each of a male's cells. Males with 47,XYY syndrome have one X chromosome and two Y chromosomes, for a total of 47 chromosomes per cell. Researchers are not yet certain why an extra copy of the Y chromosome is associated with tall stature and learning problems in some boys and men. These effects are variable and often minimal or undetectable. When chromosome surveys were first done in the 1960s, it was reported that a higher than expected number of men in prisons were found to have an extra Y chromosome, so that for a while it was thought to predispose a boy to antisocial behavior (and was dubbed the "criminal karyotype"). Better population surveys have since demonstrated that the association was simply that boys and men with learning problems are more likely statistically to spend time in prison and that there is no other independent statistical association with extra Y. The "criminal karyotype" concept is inaccurate and obsolete.

Greater degrees of Y chromosome polysomy (e.g., XYYYY) are very rare. Rarely, males may have more than one extra copy of the Y chromosome in every cell (polysomy Y). The extra genetic material in these cases can lead to skeletal abnormalities, decreased IQ, and delayed development, but the features of these conditions are variable.

There are also problems that arise from having an incomplete Y chromosome: the usual karyotype in these cases is 46X, plus a fragment of Y. This usually results in defective testicular development, such that the infant may or may not have fully formed male genitalia internally or externally. The full range of ambiguity of structure may occur, especially if mosaicism is present. When the Y fragment is minimal and nonfunctional, the child usually is a girl with the features of Turner syndrome but a risk of malignancy.

Klinefelter's syndrome (47, XXY) is not an aneuploidy of the Y chromosome, but the extra X chromosome usually results in defective postnatal testicular function. This does not seem to be due to direct interference with expression of Y genes, and the mechanism is not fully understood.

Genetic genealogy

In human genetic genealogy (the application of genetics to traditional genealogy) use of the information contained in the Y chromosome is of particular interest since, unlike other genes, the Y chromosome is passed exclusively from father to son. See www.smgf.org or for more information.

References

Cordum, H.S., et. al. (2003) The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature, 423, 825-837
Rozen, S., et. al. (2003) Abundant gene conversion between arms of palindromes in human and ape Y chromosomes. Nature, 423, 873-876.

External links

http://www.ncbi.nlm.nih.gov/mapview/maps.cgi?taxid=9606&chr=Y
Human Genome Project Information — Human Chromosome Y Launchpad
On Topic — The Y Chromosome - From the Whitehead Institute for Biomedical Research
Nature — focus on the Y chomosome
National Human Genome Research Institute (NHGRI) — Use of Novel Mechanism Preserves Y Chromosome Genes
Y Chromosome Consortium (YCC)

Chromosomes

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