Y chromosome

Human Y-chromatid

The Y chromosome is one of the two sex-determining chromosomes in most mammals, including humans. In mammals, it contains the gene SRY, which triggers testis development if present. The human Y chromosome is composed of about 60 million base pairs. DNA in the Y chromosome is passed from father to son, thus tracking many surnames. Y-DNA analysis is thus used in family history research.

Contents

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 a gene, SRY, which triggers embryonic development as a male. The Y chromosomes of humans and other mammals also contain other genes needed for normal sperm production.

There are exceptions, however. For example, the platypus relies on an XY sex-determination system based on five pairs of chromosomes [1]. Platypus sex chromosomes in fact appear to bear a much stronger homology (similarity) with the avian Z chromosome[2], and the SRY gene so central to sex-determination in most other mammals is apparently not involved in platypus sex-determination[3]. Among humans, some men have two Xs and a Y ("XXY", see Klinefelter's syndrome), or one X and two Ys (see XYY syndrome), and some women have three Xs or a single X instead of a double X ("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.

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 (meaning they contain both male and female gametes in the same individual).

Origin

The X and Y chromosomes are thought to have evolved from a pair of identical chromosomes[4][5], 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[6]. 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.[7].

Until recently, the X and Y chromosomes were thought to have diverged around 300 million years ago. However recent research[8], particularly that stemming from the sequencing of the platypus genome[2], has suggested that the XY sex-determination system wouldn't have been present more than 166 million years ago, at the split of the monotremes from other mammals[3]. This reestimation of the age of the therian XY system is based on the finding that sequences that are on the X chromosomes of marsupials and eutherian mammals are present on the autosomes of platypus and birds[3]. The older estimate was based on erroneous reports that the platypus X chromosomes contained these sequences [9][10].

Recombination inhibition

Recombination between the X and Y chromosomes proved harmful - it resulted in males without necessary genes formerly found on the Y 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[6]. 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

The human Y chromosome has lost 1,393 of its 1,438 original genes over the course of its existence. With a rate of genetic loss of 4.6 genes per million years, the Y chromosome may potentially lose complete function within the next 10 million years.[11] Comparative genomic analysis, however, reveals that many mammalian species are experiencing a similar loss of function in their heterozygous sex chromosome. Degeneration may simply be the fate of all nonrecombining sex chromosomes due to three common evolutionary forces: high mutation rate, inefficient selection and genetic drift.[12] On the other hand, recent comparisons of the human and chimpanzee Y chromosomes show that the human Y chromosome has not lost any genes since the divergence of humans and chimpanzees between 6-7 million years ago,[13] providing direct evidence that the linear extrapolation model may be flawed.

High Mutation Rate

The human Y chromosome is particularly exposed to high mutation rates due to the environment in which it is housed. The Y chromosome is passed exclusively through sperm, which undergo multiple cell divisions during gametogenesis. Each cellular division provides further opportunity to accumulate base pair mutations. Additionally, sperm are stored in the highly oxidative environment of the testis, which encourages further mutation. These two conditions combined put the Y chromosome at a risk of mutation 4.8 times greater than the rest of the genome.[12]

Inefficient Selection

Without the ability to recombine during meiosis, the Y chromosome is unable to expose individual alleles to natural selection. Deleterious alleles are allowed to "hitchhike" with beneficial neighbors, thus propagating maladapted alleles in to the next generation. Conversely, advantageous alleles may be selected against if they are surrounded by harmful alleles (background selection). This inability to sort through its gene content, the Y chromosome is particularly prone to the accumulation of "junk" DNA. Massive accumulations of retrotransposable elements are scattered throughout the Y.[12] The random insertion of DNA segments often disrupt encoded gene sequences and render them nonfunctional. However, the Y chromosome has no way of weeding out these "jumping genes". Without the ability to isolate alleles, selection cannot effectively act upon them.

Genetic Drift

Even if a well adapted Y chromosome manages to maintain genetic activity by avoiding mutation accumulation, there is no guarantee it will be passed down to the next generation. The population size of the Y chromosome is inherently limited to 1/4 that of autosomes: diploid organisms contain two copies of autosomal chromosomes while only half the population contains 1 Y chromosome. Thus, genetic drift is an exceptionally strong force acting upon the Y chromosome. Through sheer random assortment, an adult male may never pass on his Y chromosome if he only has female offspring. Thus, although a male may have a well adapted Y chromosome free of excessive mutation, it may never make it in to the next gene pool.[12] The repeat random loss of well-adapted Y chromosomes, coupled with the tendency of the Y chromosome to evolve to have more deleterious mutations rather than less for reasons described above, contributes to the species-wide degeneration of Y chromosomes through Muller's ratchet.[14]

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.[15] 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

In the terminal stages of the degeneration of the Y chromosome, other chromosomes increasingly take over genes and functions formerly associated with it. Finally, the Y chromosome disappears entirely, and a new sex-determining system arises.[16] Several species of rodent in the sister families Muridae and Cricetidae have reached these stages,[17][18] in the following ways:

Outside of the rodent family, the black muntjac, Muntiacus crinifrons, evolved new X and Y chromosomes through fusions of the ancestral sex chromosomes and autosomes.[27] Primate Y chromosomes, including in humans, have degenerated so much that primates will also evolve new sex determination systems relatively soon, in about 14 million years in humans.[16][28]

Human Y chromosome

In humans, the Y chromosome spans about 58 million base pairs (the building blocks of DNA) and represents approximately 2% of the total DNA in a male cell[29]. The human Y chromosome contains 86[30] genes, which code for only 23 distinct proteins. Traits that are inherited via the Y chromosome are called holandric traits.

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. The bulk of the Y chromosome which does not recombine is called the "NRY" or non-recombining region of the Y chromosome.[31] It is the SNPs in this region which are used for tracing direct paternal ancestral lines.

Genes

Not including pseudoautosomal genes, genes include:

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 roughly half 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.

Defective 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
Main article: Klinefelter's syndrome

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

XYY
Main article: 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.[32] See www.smgf.org for more information. Mitochondrial DNA, maternally inherited, is used in an analogous way to trace the maternal line.

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 Drosophila, some other insects, some fish, some reptiles, and some plants. In Drosophila melanogaster, the Y chromosome does not trigger male development. Instead, sex is determined by the number of X chromosomes. The D. melanogaster Y chromosome does contain genes necessary for male fertility. So XXY D. melanogaster are female, and D. melanogaster with a single X (X0), are male but sterile. There are some species of Drosophila in which X0 males are both viable and fertile.

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

References

  1. ↑ Grützner F, Rens W, Tsend-Ayush E, et al. (2004). "In the platypus a meiotic chain of ten sex chromosomes shares genes with the bird Z and mammal X chromosomes". Nature 432 (7019): 913–917. doi:10.1038/nature03021. PMID 15502814. 
  2. ↑ 2.0 2.1 Warren WC, Hillier LDW, Graves JAM, et al. (2008). "Genome analysis of the platypus reveals unique signatures of evolution". Nature 453 (7192): 175–183. doi:10.1038/nature06936. PMID 18464734. PMC 2803040. http://www.nature.com/nature/journal/v453/n7192/full/nature06936.html. 
  3. ↑ 3.0 3.1 3.2 Veyrunes F, Waters PD, Miethke P, et al. (2008). "Bird-like sex chromosomes of platypus imply recent origin of mammal sex chromosomes". Genome Research 18 (6): 965–973. doi:10.1101/gr.7101908. PMID 18463302. PMC 2413164. http://genome.cshlp.org/content/18/6/965.abstract. 
  4. ↑ Muller, HJ (1914). "A gene for the fourth chromosome of Drosophila". Journal of Experimental Zoology 17 (3): 325–336. doi:10.1002/jez.1400170303. 
  5. ↑ Lahn B, Page D (1999). "Four evolutionary strata on the human X chromosome". Science 286 (5441): 964–7. doi:10.1126/science.286.5441.964. PMID 10542153. 
  6. ↑ 6.0 6.1 Graves J.A.M. (2006). "Sex chromosome specialization and degeneration in mammals". Cell 124 (5): 901–14. doi:10.1016/j.cell.2006.02.024. PMID 16530039. 
  7. ↑ Graves J.A.M., Koina E., Sankovic N. (2006). "How the gene content of human sex chromosomes evolved". Curr Opin Genet Dev 16 (3): 219–24. doi:10.1016/j.gde.2006.04.007. PMID 16650758. 
  8. ↑ Human Male Still A Work in Progress
  9. ↑ Nature 432, 913-917 (16 December 2004) | doi:10.1038/nature03021
  10. ↑ DOI 10.1007/BF00360536
  11. ↑ Graves, J.A.M. 2004. The degenerate Y chromosome- can conversion save it? Reproduction Fertility and Development 16:527-534.
  12. ↑ 12.0 12.1 12.2 12.3 Graves, J.A.M. 2006. Sex chromosome specialization and degeneration in mammals. Cell 124:901-914
  13. ↑ http://www.ncbi.nlm.nih.gov/pubmed/16136134
  14. ↑ Charlesworth, B., and D. Charlesworth. 2000. The degeneration of Y chromosomes. Philosophical Transactions of the Royal Society of London Series B-Biological Sciences 355:1563-1572.
  15. ↑ Rozen S, Skaletsky H, Marszalek J, Minx P, Cordum H, Waterston R, Wilson R, Page D (2003). "Abundant gene conversion between arms of palindromes in human and ape Y chromosomes". Nature 423 (6942): 873–6. doi:10.1038/nature01723. PMID 12815433. 
  16. ↑ 16.0 16.1 Graves, J. A. M. 2006. Sex chromosome specialization and degeneration in mammals. Cell 124:901-914.
  17. ↑ Marchal, J. A., M. J. Acosta, M. Bullejos, R. D. de la Guardia, and A. Sanchez. 2003, Sex chromosomes, sex determination, and sex-linked sequences in Microtidae:266-273.
  18. ↑ Wilson, M. A., and K. D. Makova. 2009. Genomic analyses of sex chromosome evolution. Annual Review of Genomics and Human Genetics 10:333-354.
  19. ↑ Just, W., A. Baumstark, A. Suss, A. Graphodatsky, W. Rens, N. Schafer, I. Bakloushinskaya et al. 2007. Ellobius lutescens: Sex determination and sex chromosome. Sexual Development 1:211-221.
  20. ↑ 20.0 20.1 Graves 2006
  21. ↑ Arakawa, Y., C. Nishida-Umehara, Y. Matsuda, S. Sutou, and H. Suzuki. 2002. X-chromosomal localization of mammalian Y-linked genes in two XO species of the Ryukyu spiny rat. Cytogenetic and Genome Research 99:303-309.
  22. ↑ 22.0 22.1 Arakawa et al. 2002
  23. ↑ Hoekstra, H. E., and S. V. Edwards. 2000. Multiple origins of XY female mice (genus Akodon): phylogenetic and chromosomal evidence. Proceedings of the Royal Society of London Series B-Biological Sciences 267:1825-1831.
  24. ↑ Marchal et al. 2003
  25. ↑ Ortiz, M. I., E. Pinna-Senn, G. Dalmasso, and J. A. Lisanti. 2009. Chromosomal aspects and inheritance of the XY female condition in Akodon azarae (Rodentia, Sigmodontinae). Mammalian Biology 74:125-129.
  26. ↑ Charlesworth, B., and N. D. Dempsey. 2001. A model of the evolution of the unusual sex chromosome system of Microtus oregoni. Heredity 86:387-394.
  27. ↑ Zhou, Q., J. Wang, L. Huang, W. H. Nie, J. H. Wang, Y. Liu, X. Y. Zhao et al. 2008. Sex chromosomes in the black muntjac recapitulate incipient evolution of mammalian sex chromosomes. Genome Biology 9:11.
  28. ↑ Goto, H., L. Peng, and K. D. Makova. 2009. Evolution of X-degenerate Y chromosome genes in greater apes: conservation of gene content in human and gorilla, but not chimpanzee. Journal of Molecular Evolution 68:134-144.
  29. ↑ National Library of Medicine's Genetic Home Reference
  30. ↑ "Ensembl Human MapView release 43". February 2007. http://www.ensembl.org/Homo_sapiens/mapview?chr=Y. Retrieved 2007-04-14. 
  31. ↑ ScienceDaily.com Apr. 3, 2008
  32. ↑ See www.smgf.org for more information.

External links

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Sex chromosome
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