The Y chromosome is the sex-determining chromosome in humans and most other mammals. In mammals, it contains the gene SRY, which triggers testis development, thus determining sex.

Overview

Most mammals have one pair of sex chromosomes in each cell. Males have one Y chromosome and one X chromosome, while females have two X chromosomes. In mammals, the Y chromosome contains the gene that triggers embryonic development as a male. This gene is SRY. Other genes (in addition to SRY) on the Y chromosomes of men and other mammals are needed for normal sperm production.

There are exceptions, however. Among humans, some men have two X's and a Y ("XXY", see Klinefelter's syndrome), or one X and two Y's (see XYY syndrome), and some women have three Xs or a single X (and no Y, "X0", see Turner syndrome). There are other exceptions in which SRY is damaged (leading to an XY female), or copied to the X (leading to an XX male). For related phenomena see Androgen insensitivity syndrome and Intersex.

Presence or absence of the Y-chromosome is a method of sex determination.

Origins and evolution

Before Y-chromosome

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, for example the frog or toad.

Origin

The X and Y chromosomes diverged around 300 million years ago from a pair of identical chromosomes^[1], termed autosomes, when an ancestral mammal developed an allelic variation, a so-called 'sex locus' - simply possessing this allele caused the organism to be male^[2] The chromosome with this allele became the Y chromosome, while the other member of the pair became the X chromosome. Over time, genes which were beneficial for males and harmful to (or had no effect on) females either developed on the Y chromosome, or were acquired through the process of translocation.^[3]

Recombination inhibition

Recombination between the X and Y chromosomes proved harmful - it resulted in males without necessary genes formerly found on the X chromosome, and females with unnecessary or even harmful genes previously only found on the Y chromosome. As a result, genes beneficial to males accumulated near the sex-determining genes, and recombination in this region was suppressed in order to preserve this male specific region^[4]. Over time, the Y chromosome changed in such a way as to inhibit the areas around the sex determining genes from recombining at all with the X chromosome. As a result of this process 95% of the human Y chromosome is unable to recombine.

Shrinking

With time, larger and larger areas became unable to recombine with the X chromosome. This caused its own problems: without recombination, the removal of harmful mutations from chromosomes becomes increasingly difficult. These harmful mutations continued to damage Y-unique genes until several finally stopped functioning and became genetic junk; this was eventually removed from the Y chromosome.

Today, the human Y chromosome itself contains only 86 working genes;^[5] compare this to close to 1000 working genes on the X chromosome. In some animals, Y degradation is even more severe. The 10-12 Mb dunnart Y chromosome, with only four characterised genes; among them the SRY gene, is the smallest known mammalian Y chromosome. ^[6]

Gene conversion

In 2003, researchers from MIT discovered a 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.^[7] 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. In other words, since the Y chromosome is single, it has duplicates of its genes on itself instead of having a second, homologous, chromosome. When errors occur, it can use other parts of itself as a template to correct them.

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.

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.
• The Y chromosome remains, containing only the SRY gene.

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 86^[5] genes, which code for only 23 distinct proteins.

The human Y chromosome is unable to recombine with the X chromosome, except for small pieces of pseudoautosomal regions at the telomeres (which comprise about 5% of the chromosome's length). These regions are relics of ancient homology between the X and Y 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)

Y-Chromosome-linked diseases

Y-Chromosome-linked diseases can be of more common types, or very rare ones. Yet, the rare ones still have importance in understanding the function of the Y-chromosome in the normal case.

More common

No vital genes reside only on the Y chromosome, since 50% of humans (females) 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). However, having two X-chromosomes and one Y-chromosome has similar effects. On the other hand, having Y-chromosome polysomy has other effects than masculinization.

Defect Y-chromosome

This results in the person presenting a female phenotype even though that person possesses an XY karyotype (i.e., is born with female-like genitalia). The lack of the second X results in infertility. In other words, viewed from opposite direction, the person goes through defeminization but fails to complete masculinization.

The cause can be seen as 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 or mixed gonadal dysgenesis.

XXY

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

XYY

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. 47,XYY males have one X chromosome and two Y chromosomes, for a total of 47 chromosomes per cell. Researchers have found that an extra copy of the Y chromosome is associated with increased stature and an increased incidence of learning problems in some boys and men, but the effects are variable, often minimal, and the vast majority do not know their karyotype. When chromosome surveys were done in the mid-1960s in British secure hospitals for the developmentally disabled, a higher than expected number of patients were found to have an extra Y chromosome. The patients were mischaracterized as aggressive and criminal, so that for a while an extra Y chromosome was believed to predispose a boy to antisocial behavior (and was dubbed the "criminal karyotype"). Subsequently, in 1968 in Scotland the only ever comprehensive nationwide chromosome survey of prisons found no overrepresentation of 47,XYY men, and later studies found 47,XYY boys and men had the same rate of criminal convictions as 46,XY boys and men of equal intelligence. Thus, the "criminal karyotype" concept is inaccurate and obsolete.

Rare

The following Y-Chromosome-linked diseases are rare, but notable because of their elucidating of the nature of the Y-chromosome.

More than two Y chromosomes

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

XX male syndrome

XX male syndrome occurs when there has been a recombination in the formation of the male gametes, causing the SRY-portion of the Y chromosome to move to the X chromosome. When such an X chromosome contributes to the child, the development will lead to a male, because of the SRY gene.

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.^[8] See www.smgf.org for more information.

Non-mammal Y-chromosome

Many groups of organisms in addition to mammals have Y chromosomes, but these Y chromosomes do not share common ancestry with mammalian Y chromosomes. Such groups include fruit flies (Drosophila melanogaster and relatives), some other insects, some fish, some reptiles, and some plants. In fruit flies, the Y chromosome does not trigger male development. Instead, sex is determined by the number of X chromosomes. So XXY fruit flies are female, and fruit flies with a single X (X0), are male but sterile.

ZW-chromosomes

Other organisms have mirror image sex chromosomes: the female is "XY" and the male is "XX", but by convention biologists call a "female Y" a W chromosome and the other a Z chromosome. For example, female birds, snakes, and butterflies have ZW sex chromosomes, and males have ZZ sex chromosomes.

See also

• Human Y-chromosome DNA haplogroups
• DNA Y-chromosome Segment (DYS)
• List of DYS markers
• Y-chromosomal Adam
• Y-chromosomal Aaron
• genetic genealogy
• genealogical DNA test
• Y chromosome Short Tandem Repeat (STR)
• Y linkage
• X chromosome

References

• Skaletsky, 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

• Genetic Genealogy: About the use of mtDNA and Y chromosome analysis in ancestry testing
• http://www.ensembl.org/Homo_sapiens/mapview?chr=Y
• 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
• Ysearch.org - Public Y-DNA database
• Y Chromosome Consortium (YCC)

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