Y chromosome#Recombination inhibition

The Y chromosome was identified as a sex-determining chromosome by Nettie Stevens at Bryn Mawr College in 1905 during a study of the mealworm Tenebrio molitor. Edmund Beecher Wilson independently discovered the same mechanisms the same year, working with Hemiptera. Stevens proposed that chromosomes always existed in pairs and that the smaller chromosome (now labelled "Y") was the pair of the X chromosome discovered in 1890 by Hermann Henking. She realized that the previous idea of Clarence Erwin McClung, that the X chromosome determines sex, was wrong and that sex determination is, in fact, due to the presence or absence of the Y chromosome. In the early 1920s, Theophilus Painter determined that X and Y chromosomes determined sex in humans (and other mammals).{{cite journal | vauthors = Glass B | title = Theophilus Shickel Painter: August 22, 1889-October 5, 1969 | journal = Biographical Memoirs of the National Academy of Sciences | volume = 59 | issue = | pages = 309–37 | date = 1990 | pmid = 11616163 | doi = | url = http://www.nasonline.org/publications/biographical-memoirs/memoir-pdfs/painter-theophilus-shickel.pdf }}

The chromosome was given the name "Y" simply to follow on from Henking's "X" alphabetically.{{cite book | vauthors = Bainbridge D |title=X in Sex : How the X Chromosome Controls |date=2003 |publisher=Harvard University Press |location=Cambridge, Mass. |isbn=978-0-674-01621-7}}{{cite book | vauthors = Schwartz J | title = In Pursuit of the Gene: From Darwin to DNA | pages = 170–2 |publisher=Harvard University Press |location=Cambridge, Mass. | date = 2009| isbn = 978-0-674-03491-4 }} The idea that the Y chromosome was named after its similarity in appearance to the letter "Y" is mistaken. All chromosomes normally appear as an amorphous blob under the microscope and only take on a well-defined shape during mitosis. This shape is vaguely X-shaped for all chromosomes. It is entirely coincidental that the Y chromosome, during mitosis, has two very short branches which can look merged under the microscope and appear as the descender of a Y-shape.{{rp|65–66}}

Most therian mammals have only 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.{{citation needed|date=November 2023}}

Among humans, males with an extra X chromosome have Klinefelter Syndrome, and males with an extra Y chromosome have Jacob's Syndrome, as the presence of the Y chromosome determines sex.{{Cite journal |vauthors=Hake L, O'Connor C |date=2008 |title=Genetic Mechanisms of Sex Determination |url=https://www.nature.com/scitable/topicpage/genetic-mechanisms-of-sex-determination-314/ |url-status=live |journal=Nature Education |series=Learn Science at Scitable |volume=1 |issue=1 |pages=25 |archive-url=https://web.archive.org/web/20210428022557/https://www.nature.com/scitable/topicpage/genetic-mechanisms-of-sex-determination-314/ |archive-date=2021-04-28}} Other conditions include females with three X chromosomes (or Trisomy X), and Monosomy X (or Turner Syndrome), females that are missing the second X chromosome. Other conditions that affect the development of an XY fetus, such as Swyer Syndrome, which is caused by a mutation in genes such as the SRY gene or MAP3K1.{{cite web |title=Swyer syndrome — Symptoms, Causes, Treatment {{!}} NORD |url=https://rarediseases.org/rare-diseases/swyer-syndrome/#:~:text=Mutations%20of%20the%20WNT4,dominant%20pattern |access-date=2023-09-12 |website=rarediseases.org |language=en-US}}

Many ectothermic vertebrates have no sex chromosomes.{{cite journal | vauthors = Devlin RH, Nagahama Y |date=2002-06-21 |title=Sex determination and sex differentiation in fish: an overview of genetic, physiological, and environmental influences |url=https://www.sciencedirect.com/science/article/pii/S0044848602000571 |journal=Aquaculture |series=Sex determination and sex differentation in fish |volume=208 |issue=3 |pages=191–364 |doi=10.1016/S0044-8486(02)00057-1 |bibcode=2002Aquac.208..191D |issn=0044-8486|url-access=subscription }} If these species have different sexes, sex is determined environmentally rather than genetically. For some species, especially reptiles, sex depends on the incubation temperature.{{cite book |first1=Michael J.F. |last1=Barresi |first2=Scott F. |last2=Gilbert |chapter=6. Sex Determination and Gametogenesis §6.4 Environmental Sex Determination in Reptiles |chapter-url=https://www.oxfordsciencetrove.com/view/10.1093/hesc/9780197574591.001.0001/isbn-9780197574591-book-part-6 |title=Developmental Biology |publisher=Oxford University Press |edition=13th |date=2023 |isbn=978-0-19-757459-1 }}
{{cite book | vauthors = Gilbert SF | chapter = Environmental Sex Determination |date=2000 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK9989/ |title=Developmental Biology | edition = 6th |id=NBK9989 |isbn=0-87893-243-7 |publisher=Sinauer Associates |page=60}} Some vertebrates are hermaphrodites, though hermaphroditic species are most commonly sequential, meaning the organism switches sex, producing male or female gametes at different points in its life, but never producing both at the same time. This is opposed to simultaneous hermaphroditism, where the same organism produces male and female gametes at the same time. Most simultaneous hermaphrodite species are invertebrates, and among vertebrates, simultaneous hermaphroditism has only been discovered in a few orders of fish.{{cite journal | vauthors = Kuwamura T, Sunobe T, Sakai Y, Kadota T, Sawada K |date=2020-07-01 |title=Hermaphroditism in fishes: an annotated list of species, phylogeny, and mating system |journal=Ichthyological Research |volume=67 |issue=3 |pages=341–360 |doi=10.1007/s10228-020-00754-6 |bibcode=2020IchtR..67..341K |s2cid=254168012 |issn=1616-3915|doi-access=free }}

The X and Y chromosomes are thought to have evolved from a pair of identical chromosomes,{{cite journal | vauthors = Muller HJ |title=A gene for the fourth chromosome of Drosophila |journal=Journal of Experimental Zoology |volume=17 |issue=3 |pages=325–336 |year=1914 |doi=10.1002/jez.1400170303|bibcode=1914JEZ....17..325M |url=https://zenodo.org/record/1426868 }}{{cite journal | vauthors = Lahn BT, Page DC | title = Four evolutionary strata on the human X chromosome | journal = Science | volume = 286 | issue = 5441 | pages = 964–7 | date = October 1999 | pmid = 10542153 | doi = 10.1126/science.286.5441.964 }} termed autosomes, when an ancestral animal developed an allelic variation (a so-called "sex locus") and simply possessing this allele caused the organism to be male. The chromosome with this allele became the Y chromosome, while the other member of the pair became the X chromosome. Over time, genes that were beneficial for males and harmful to (or had no effect on) females either developed on the Y chromosome or were acquired by the Y chromosome through the process of translocation.{{cite journal | vauthors = Graves JA, Koina E, Sankovic N | title = How the gene content of human sex chromosomes evolved | journal = Current Opinion in Genetics & Development | volume = 16 | issue = 3 | pages = 219–224 | date = June 2006 | pmid = 16650758 | doi = 10.1016/j.gde.2006.04.007 }}

Until recently, the X and Y chromosomes in mammals were thought to have diverged around 300 million years ago.{{cite journal | vauthors = Bachtrog D | title = Y-chromosome evolution: emerging insights into processes of Y-chromosome degeneration | journal = Nature Reviews. Genetics | volume = 14 | issue = 2 | pages = 113–124 | date = February 2013 | pmid = 23329112 | pmc = 4120474 | doi = 10.1038/nrg3366 }} However, research published in 2008 analyzing the platypus genome suggested that the XY sex-determination system would not have been present more than 166 million years ago, when monotremes split from other mammals. This re-estimation 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 not present on the autosomes of platypus and birds. The older estimate was based on erroneous reports that the platypus X chromosomes contained these sequences.{{cite journal | vauthors = Watson JM, Riggs A, Graves JA | title = Gene mapping studies confirm the homology between the platypus X and echidna X1 chromosomes and identify a conserved ancestral monotreme X chromosome | journal = Chromosoma | volume = 101 | issue = 10 | pages = 596–601 | date = October 1992 | pmid = 1424984 | doi = 10.1007/BF00360536 | s2cid = 26978106 }}

Most chromosomes recombine during meiosis. However, in males, the X and Y pair in a shared region known as the pseudoautosomal region (PAR).{{cite web | vauthors = LeMieux J |date=2020-05-29 |title=On PAR: How X and Y Chromosomes Recombine During Meiosis |url=https://www.genengnews.com/news/on-par-how-x-and-y-chromosomes-recombine-during-meiosis/ |access-date=2023-11-13 |website=GEN — Genetic Engineering and Biotechnology News |language=en-US}} The PAR undergoes frequent recombination between the X and Y chromosomes, but recombination is suppressed in other regions of the Y chromosome. These regions contain sex-determining and other male-specific genes.{{cite journal | vauthors = Peneder P, Wallner B, Vogl C | title = Exchange of genetic information between therian X and Y chromosome gametologs in old evolutionary strata | journal = Ecology and Evolution | volume = 7 | issue = 20 | pages = 8478–8487 | date = October 2017 | pmid = 29075464 | pmc = 5648654 | doi = 10.1002/ece3.3278 | bibcode = 2017EcoEv...7.8478P }} Without this suppression, these genes could be lost from the Y chromosome from recombination and cause issues such as infertility.{{cite journal |vauthors=Dhanoa JK, Mukhopadhyay CS, Arora JS |title=Y-chromosomal genes affecting male fertility: A review |journal=Vet World |volume=9 |issue=7 |pages=783–91 |date=July 2016 |pmid=27536043 |pmc=4983133 |doi=10.14202/vetworld.2016.783-791 }}

The lack of recombination across the majority of the Y chromosome makes it a useful tool in studying human evolution, since recombination complicates the mathematical models used to trace ancestries.{{cite journal | vauthors = Brookfield JF | title = Human evolution. Y-chromosome clues to human ancestry | journal = Current Biology | volume = 5 | issue = 10 | pages = 1114–1115 | date = October 1995 | pmid = 8548280 | doi = 10.1016/S0960-9822(95)00224-7 | s2cid = 16081591 | doi-access = free | bibcode = 1995CBio....5.1114B }}

By one estimate, the human Y chromosome has lost 1,393 of its 1,438 original genes over the course of its existence, and linear extrapolation of this 1,393-gene loss over 300 million years gives a rate of genetic loss of 4.6 genes per million years.{{cite journal | vauthors = Graves JA | title = The degenerate Y chromosome--can conversion save it? | journal = Reproduction, Fertility, and Development | volume = 16 | issue = 5 | pages = 527–534 | year = 2004 | pmid = 15367368 | doi = 10.1071/RD03096 }} Continued loss of genes at this rate would result in a Y chromosome with no functional genes – that is the Y chromosome would lose complete function – within the next 10 million years, or half that time with the current age estimate of 160 million years.{{cite journal | vauthors = Goto H, Peng L, Makova KD | title = Evolution of X-degenerate Y chromosome genes in greater apes: conservation of gene content in human and gorilla, but not chimpanzee | journal = Journal of Molecular Evolution | volume = 68 | issue = 2 | pages = 134–144 | date = February 2009 | pmid = 19142680 | doi = 10.1007/s00239-008-9189-y | s2cid = 24010421 | bibcode = 2009JMolE..68..134G }} Comparative genomic analysis 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 non-recombining sex chromosomes, due to three common evolutionary forces: high mutation rate, inefficient selection, and genetic drift.{{cite journal | vauthors = Graves JA | title = Sex chromosome specialization and degeneration in mammals | journal = Cell | volume = 124 | issue = 5 | pages = 901–914 | date = March 2006 | pmid = 16530039 | doi = 10.1016/j.cell.2006.02.024 | s2cid = 8379688 | doi-access = free }}

With a 30% difference between humans and chimpanzees, the Y chromosome is one of the fastest-evolving parts of the human genome.{{cite news | vauthors = Wade N |date=January 13, 2010 |title=Male Chromosome May Evolve Fastest |newspaper=New York Times |url=https://www.nytimes.com/2010/01/14/science/14gene.html}} However, these changes have been limited to non-coding sequences and comparisons of the human and chimpanzee Y chromosomes (first published in 2005) show that the human Y chromosome has not lost any genes since the divergence of humans and chimpanzees between 6–7 million years ago.{{cite journal | vauthors = Hughes JF, Skaletsky H, Pyntikova T, Minx PJ, Graves T, Rozen S, Wilson RK, Page DC | display-authors = 6 | title = Conservation of Y-linked genes during human evolution revealed by comparative sequencing in chimpanzee | journal = Nature | volume = 437 | issue = 7055 | pages = 100–103 | date = September 2005 | pmid = 16136134 | doi = 10.1038/nature04101 | s2cid = 4418662 | bibcode = 2005Natur.437..100H }} Additionally, a scientific report in 2012 stated that only one gene had been lost since humans diverged from the rhesus macaque 25 million years ago.{{cite web | vauthors = Hsu C |title=Biologists Debunk the 'Rotting' Y Chromosome Theory, Men Will Still Exist |url=http://www.medicaldaily.com/news/20120222/9163/y-chromosome-chromosome-theory-men-extinct-monkey-x-chromosome-biology.htm |publisher=Medical Daily |access-date=2012-02-23 |archive-date=2012-02-25 |archive-url=https://web.archive.org/web/20120225011411/http://www.medicaldaily.com/news/20120222/9163/y-chromosome-chromosome-theory-men-extinct-monkey-x-chromosome-biology.htm |url-status=dead }} These facts provide direct evidence that the linear extrapolation model is flawed and suggest that the current human Y chromosome is either no longer shrinking or is shrinking at a much slower rate than the 4.6 genes per million years estimated by the linear extrapolation model.{{citation needed|date=July 2023}}

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 greater opportunity of mutation than the rest of the genome. The increased mutation opportunity for the Y chromosome is reported by Graves as a factor 4.8. However, her original reference obtains this number for the relative mutation rates in male and female germ lines for the lineage leading to humans.{{cite journal | vauthors = Lindblad-Toh K, Wade CM, Mikkelsen TS, Karlsson EK, Jaffe DB, Kamal M, Clamp M, Chang JL, Kulbokas EJ, Zody MC, Mauceli E, Xie X, Breen M, Wayne RK, Ostrander EA, Ponting CP, Galibert F, Smith DR, DeJong PJ, Kirkness E, Alvarez P, Biagi T, Brockman W, Butler J, Chin CW, Cook A, Cuff J, Daly MJ, DeCaprio D, Gnerre S, Grabherr M, Kellis M, Kleber M, Bardeleben C, Goodstadt L, Heger A, Hitte C, Kim L, Koepfli KP, Parker HG, Pollinger JP, Searle SM, Sutter NB, Thomas R, Webber C, Baldwin J, Abebe A, Abouelleil A, Aftuck L, Ait-Zahra M, Aldredge T, Allen N, An P, Anderson S, Antoine C, Arachchi H, Aslam A, Ayotte L, Bachantsang P, Barry A, Bayul T, Benamara M, Berlin A, Bessette D, Blitshteyn B, Bloom T, Blye J, Boguslavskiy L, Bonnet C, Boukhgalter B, Brown A, Cahill P, Calixte N, Camarata J, Cheshatsang Y, Chu J, Citroen M, Collymore A, Cooke P, Dawoe T, Daza R, Decktor K, DeGray S, Dhargay N, Dooley K, Dooley K, Dorje P, Dorjee K, Dorris L, Duffey N, Dupes A, Egbiremolen O, Elong R, Falk J, Farina A, Faro S, Ferguson D, Ferreira P, Fisher S, FitzGerald M, Foley K, Foley C, Franke A, Friedrich D, Gage D, Garber M, Gearin G, Giannoukos G, Goode T, Goyette A, Graham J, Grandbois E, Gyaltsen K, Hafez N, Hagopian D, Hagos B, Hall J, Healy C, Hegarty R, Honan T, Horn A, Houde N, Hughes L, Hunnicutt L, Husby M, Jester B, Jones C, Kamat A, Kanga B, Kells C, Khazanovich D, Kieu AC, Kisner P, Kumar M, Lance K, Landers T, Lara M, Lee W, Leger JP, Lennon N, Leuper L, LeVine S, Liu J, Liu X, Lokyitsang Y, Lokyitsang T, Lui A, Macdonald J, Major J, Marabella R, Maru K, Matthews C, McDonough S, Mehta T, Meldrim J, Melnikov A, Meneus L, Mihalev A, Mihova T, Miller K, Mittelman R, Mlenga V, Mulrain L, Munson G, Navidi A, Naylor J, Nguyen T, Nguyen N, Nguyen C, Nguyen T, Nicol R, Norbu N, Norbu C, Novod N, Nyima T, Olandt P, O'Neill B, O'Neill K, Osman S, Oyono L, Patti C, Perrin D, Phunkhang P, Pierre F, Priest M, Rachupka A, Raghuraman S, Rameau R, Ray V, Raymond C, Rege F, Rise C, Rogers J, Rogov P, Sahalie J, Settipalli S, Sharpe T, Shea T, Sheehan M, Sherpa N, Shi J, Shih D, Sloan J, Smith C, Sparrow T, Stalker J, Stange-Thomann N, Stavropoulos S, Stone C, Stone S, Sykes S, Tchuinga P, Tenzing P, Tesfaye S, Thoulutsang D, Thoulutsang Y, Topham K, Topping I, Tsamla T, Vassiliev H, Venkataraman V, Vo A, Wangchuk T, Wangdi T, Weiand M, Wilkinson J, Wilson A, Yadav S, Yang S, Yang X, Young G, Yu Q, Zainoun J, Zembek L, Zimmer A, Lander ES | display-authors = 6 | title = Genome sequence, comparative analysis and haplotype structure of the domestic dog | journal = Nature | volume = 438 | issue = 7069 | pages = 803–819 | date = December 2005 | pmid = 16341006 | doi = 10.1038/nature04338 | doi-access = free | bibcode = 2005Natur.438..803L }}

The observation that the Y chromosome experiences little meiotic recombination and has an accelerated rate of mutation and degradative change compared to the rest of the genome suggests an evolutionary explanation for the adaptive function of meiosis with respect to the main body of genetic information. Brandeis{{cite journal | vauthors = Brandeis M | title = New-age ideas about age-old sex: separating meiosis from mating could solve a century-old conundrum | journal = Biological Reviews of the Cambridge Philosophical Society | volume = 93 | issue = 2 | pages = 801–810 | date = May 2018 | pmid = 28913952 | doi = 10.1111/brv.12367 | s2cid = 4764175 }} proposed that the basic function of meiosis (particularly meiotic recombination) is the conservation of the integrity of the genome, a proposal consistent with the idea that meiosis is an adaptation for repairing DNA damage.{{cite book | vauthors = Bernstein H, Hopf FA, Michod RE | chapter = The molecular basis of the evolution of sex | volume = 24 | pages = 323–70 | date = 1987 | pmid = 3324702 | doi = 10.1016/S0065-2660(08)60012-7 | isbn = 9780120176243 | series = Advances in Genetics | title = Molecular Genetics of Development }}

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 into the next generation. Conversely, advantageous alleles may be selected against if they are surrounded by harmful alleles (background selection). Due to this inability to sort through its gene content, the Y chromosome is particularly prone to the accumulation of non-coding DNA. Massive accumulations of retrotransposable elements are scattered throughout the Y. The random insertion of DNA segments often disrupts encoded gene sequences and renders 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.{{Citation needed|date=October 2018}}

A clear, quantitative indication of this inefficiency is the entropy rate of the Y chromosome. Whereas all other chromosomes in the human genome have entropy rates of 1.5–1.9 bits per nucleotide (compared to the theoretical maximum of exactly 2 for no redundancy), the Y chromosome's entropy rate is only 0.84.{{cite journal | vauthors = Liu Z, Venkatesh SS, Maley CC | title = Sequence space coverage, entropy of genomes and the potential to detect non-human DNA in human samples | journal = BMC Genomics | volume = 9 | issue = 1 | pages = 509 | date = October 2008 | pmid = 18973670 | pmc = 2628393 | doi = 10.1186/1471-2164-9-509 | doi-access = free }} Fig. 6, using the Lempel-Ziv estimators of entropy rate. From the definition of entropy rate, the Y chromosome has a much lower information content relative to its overall length, and is more redundant.

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 into the next gene pool. 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.{{cite journal | vauthors = Charlesworth B, Charlesworth D | title = The degeneration of Y chromosomes | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 355 | issue = 1403 | pages = 1563–1572 | date = November 2000 | pmid = 11127901 | pmc = 1692900 | doi = 10.1098/rstb.2000.0717 }}

As has been already mentioned, the Y chromosome is unable to recombine during meiosis like the other human chromosomes; however, 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.{{cite journal | vauthors = Rozen S, Skaletsky H, Marszalek JD, Minx PJ, Cordum HS, Waterston RH, Wilson RK, Page DC | display-authors = 6 | title = Abundant gene conversion between arms of palindromes in human and ape Y chromosomes | journal = Nature | volume = 423 | issue = 6942 | pages = 873–876 | date = June 2003 | pmid = 12815433 | doi = 10.1038/nature01723 | s2cid = 4323263 | bibcode = 2003Natur.423..873R }} Such a "recombination" is called gene conversion.

In the case of the Y chromosomes, the palindromes are not noncoding DNA; these strings of nucleotides 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.

Gene conversion tracts formed during meiosis are long, about 2,068 base pairs, and significantly biased towards the fixation of G or C nucleotides (GC biased).{{cite journal |vauthors=Hallast P, Balaresque P, Bowden GR, Ballereau S, Jobling MA |title=Recombination dynamics of a human Y-chromosomal palindrome: rapid GC-biased gene conversion, multi-kilobase conversion tracts, and rare inversions |journal=PLOS Genet |volume=9 |issue=7 |pages=e1003666 |date=2013 |pmid=23935520 |pmc=3723533 |doi=10.1371/journal.pgen.1003666 |doi-access=free }} The recombination intermediates preceding gene conversion were found to rarely take the alternate route of crossover recombination. The Y-Y gene conversion rate in humans is about 1.52 x 10⁻⁵ conversions/base/year.{{cite journal |vauthors=Bonito M, D'Atanasio E, Ravasini F, Cariati S, Finocchio A, Novelletto A, Trombetta B, Cruciani F |title=New insights into the evolution of human Y chromosome palindromes through mutation and gene conversion |journal=Hum Mol Genet |volume=30 |issue=23 |pages=2272–2285 |date=November 2021 |pmid=34244762 |pmc=8600007 |doi=10.1093/hmg/ddab189 }} These gene conversion events may reflect a basic function of meiosis, that of conserving the integrity of the genome.

According to some theories, in the terminal stages of the degeneration of the Y chromosome, other chromosomes may increasingly take over genes and functions formerly associated with it and finally, within the framework of this theory, the Y chromosome disappears entirely, and a new sex-determining system arises.{{POV statement|date=September 2016}}{{synthesis inline|date=September 2016}}

Several species of rodent in the sister families Muridae and Cricetidae have reached a stage where the XY system has been modified,{{cite journal | vauthors = Marchal JA, Acosta MJ, Bullejos M, Díaz de la Guardia R, Sánchez A | title = Sex chromosomes, sex determination, and sex-linked sequences in Microtidae | journal = Cytogenetic and Genome Research | volume = 101 | issue = 3–4 | pages = 266–273 | year = 2003 | pmid = 14684993 | doi = 10.1159/000074347 | s2cid = 10526522 }}{{cite journal | vauthors = Wilson MA, Makova KD | title = Genomic analyses of sex chromosome evolution | journal = Annual Review of Genomics and Human Genetics | volume = 10 | issue = 1 | pages = 333–354 | year = 2009 | pmid = 19630566 | doi = 10.1146/annurev-genom-082908-150105 }} in the following ways:

• The Transcaucasian mole vole, Ellobius lutescens, the Zaisan mole vole, Ellobius tancrei, and the Japanese spinous country rats Tokudaia osimensis and Tokudaia tokunoshimensis, have lost the Y chromosome and SRY entirely.{{cite journal | vauthors = Just W, Baumstark A, Süss A, Graphodatsky A, Rens W, Schäfer N, Bakloushinskaya I, Hameister H, Vogel W | display-authors = 6 | title = Ellobius lutescens: sex determination and sex chromosome | journal = Sexual Development | volume = 1 | issue = 4 | pages = 211–221 | year = 2007 | pmid = 18391532 | doi = 10.1159/000104771 | s2cid = 25939138 }}{{cite journal | vauthors = Arakawa Y, Nishida-Umehara C, Matsuda Y, Sutou S, Suzuki H | title = X-chromosomal localization of mammalian Y-linked genes in two XO species of the Ryukyu spiny rat | journal = Cytogenetic and Genome Research | volume = 99 | issue = 1–4 | pages = 303–9 | year = 2002 | pmid = 12900579 | doi = 10.1159/000071608 | s2cid = 39633026 }} Tokudaia spp. have relocated some other genes ancestrally present on the Y chromosome to the X chromosome. Both sexes of Tokudaia spp. and Ellobius lutescens have an XO genotype (Turner syndrome), whereas all Ellobius tancrei possess an XX genotype. The new sex-determining system(s) for these rodents remains unclear.
• The wood lemming Myopus schisticolor, the Arctic lemming, Dicrostonyx torquatus, and multiple species in the grass mouse genus Akodon have evolved fertile females who possess the genotype generally coding for males, XY, in addition to the ancestral XX female, through a variety of modifications to the X and Y chromosomes.{{cite journal | vauthors = Hoekstra HE, Edwards SV | title = Multiple origins of XY female mice (genus Akodon): phylogenetic and chromosomal evidence | journal = Proceedings. Biological Sciences | volume = 267 | issue = 1455 | pages = 1825–31 | date = September 2000 | pmid = 11052532 | pmc = 1690748 | doi = 10.1098/rspb.2000.1217 }}{{cite journal | vauthors = Ortiz MI, Pinna-Senn E, Dalmasso G, Lisanti JA |year=2009 |title=Chromosomal aspects and inheritance of the XY female condition in Akodon azarae (Rodentia, Sigmodontinae) |journal=Mammalian Biology |volume=74 |issue=2 |pages=125–9 |doi=10.1016/j.mambio.2008.03.001 |bibcode=2009MamBi..74..125O }}
• In the creeping vole, Microtus oregoni, the females, with just one X chromosome each, produce X gametes only, and the males, XY, produce Y gametes, or gametes devoid of any sex chromosome, through nondisjunction.{{cite journal | vauthors = Charlesworth B, Dempsey ND | title = A model of the evolution of the unusual sex chromosome system of Microtus oregoni | journal = Heredity | volume = 86 | issue = Pt 4 | pages = 387–394 | date = April 2001 | pmid = 11520338 | doi = 10.1046/j.1365-2540.2001.00803.x | s2cid = 34489270 | doi-access = free }}

Outside of the rodents, the black muntjac, Muntiacus crinifrons, evolved new X and Y chromosomes through fusions of the ancestral sex chromosomes and autosomes.{{cite journal | vauthors = Zhou Q, Wang J, Huang L, Nie W, Wang J, Liu Y, Zhao X, Yang F, Wang W | display-authors = 6 | title = Neo-sex chromosomes in the black muntjac recapitulate incipient evolution of mammalian sex chromosomes | journal = Genome Biology | volume = 9 | issue = 6 | pages = R98 | year = 2008 | pmid = 18554412 | pmc = 2481430 | doi = 10.1186/gb-2008-9-6-r98 | doi-access = free }}

Modern data cast doubt on the hypothesis that the Y-chromosome will disappear. This conclusion was reached by scientists who studied the Y chromosomes of rhesus monkeys. When genomically comparing the Y chromosome of rhesus monkeys and humans, scientists found very few differences, given that humans and rhesus monkeys diverged 30 million years ago.{{cite journal | vauthors = Hughes JF, Skaletsky H, Page DC | title = Sequencing of rhesus macaque Y chromosome clarifies origins and evolution of the DAZ (Deleted in AZoospermia) genes | journal = BioEssays | volume = 34 | issue = 12 | pages = 1035–44 | date = December 2012 | pmid = 23055411 | pmc = 3581811 | doi = 10.1002/bies.201200066 }}{{clarify|reason=I don't see whether this sentence is supposed to refute, explain, or support the previous sentence. Some inference step is missing.|date=August 2024}}

Outside of mammals, some organisms have lost the Y chromosome, such as most species of nematodes. However, in order for the complete elimination of Y to occur, it was necessary to develop an alternative way of determining sex (for example, by determining sex by the ratio of the X chromosome to autosomes), and any genes necessary for male function had to be moved to other chromosomes. In the meantime, modern data demonstrate the complex mechanisms of Y chromosome evolution and the fact that the disappearance of the Y chromosome is not guaranteed.

Fisher's principle outlines why almost all species using sexual reproduction have a sex ratio of 1:1. W. D. Hamilton gave the following basic explanation in his 1967 paper on "Extraordinary sex ratios",{{cite journal | vauthors = Hamilton WD | title = Extraordinary sex ratios. A sex-ratio theory for sex linkage and inbreeding has new implications in cytogenetics and entomology | journal = Science | volume = 156 | issue = 3774 | pages = 477–488 | date = April 1967 | pmid = 6021675 | doi = 10.1126/science.156.3774.477 | bibcode = 1967Sci...156..477H }} given the condition that males and females cost equal amounts to produce:

:# Suppose male births are less common than female.

:# A newborn male then has better mating prospects than a newborn female, and therefore can expect to have more offspring.

:# Therefore, parents genetically disposed to produce males tend to have more than average numbers of grandchildren born to them.

:# Therefore, the genes for male-producing tendencies spread, and male births become more common.

:# As the 1:1 sex ratio is approached, the advantage associated with producing males dies away.

:# The same reasoning holds if females are substituted for males throughout. Therefore, 1:1 is the equilibrium ratio.

Many groups of organisms in addition to therian mammals have Y chromosomes, but these Y chromosomes do not share common ancestry with therian Y chromosomes. Such groups include monotremes, 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.{{citation needed|date=May 2017}}

{{main|ZW sex-determination system}}

Other organisms have mirror image sex chromosomes: where the homogeneous sex is the male, with two Z chromosomes, and the female is the heterogeneous sex with a Z chromosome and a W chromosome.{{cite journal | vauthors = Smith JJ, Voss SR | title = Bird and mammal sex-chromosome orthologs map to the same autosomal region in a salamander (ambystoma) | journal = Genetics | volume = 177 | issue = 1 | pages = 607–613 | date = September 2007 | pmid = 17660573 | pmc = 2013703 | doi = 10.1534/genetics.107.072033 }} For example, the ZW sex-determination system is found in birds, snakes, and butterflies; the females have ZW sex chromosomes, and males have ZZ sex chromosomes.{{cite journal | vauthors = Viana PF, Ezaz T, de Bello Cioffi M, Liehr T, Al-Rikabi A, Goll LG, Rocha AM, Feldberg E | display-authors = 6 | title = Landscape of snake' sex chromosomes evolution spanning 85 MYR reveals ancestry of sequences despite distinct evolutionary trajectories | journal = Scientific Reports | volume = 10 | issue = 1 | pages = 12499 | date = July 2020 | pmid = 32719365 | pmc = 7385105 | doi = 10.1038/s41598-020-69349-5 | bibcode = 2020NatSR..1012499V }}{{cite journal | vauthors = Sahara K, Yoshido A, Traut W | title = Sex chromosome evolution in moths and butterflies | journal = Chromosome Research | volume = 20 | issue = 1 | pages = 83–94 | date = January 2012 | pmid = 22187366 | doi = 10.1007/s10577-011-9262-z | s2cid = 15130561 | doi-access = free | hdl = 2115/49121 | hdl-access = free }}

There are some species, such as the Japanese rice fish, in which the XY system is still developing and cross over between the X and Y is still possible. Because the male specific region is very small and contains no essential genes, it is even possible to artificially induce XX males and YY females to no ill effect.{{cite journal | vauthors = Schartl M | title = A comparative view on sex determination in medaka | journal = Mechanisms of Development | volume = 121 | issue = 7–8 | pages = 639–645 | date = July 2004 | pmid = 15210173 | doi = 10.1016/j.mod.2004.03.001 | s2cid = 17401686 | doi-access = }}

Monotremes like platypuses possess four or five pairs of XY sex chromosomes, each pair consisting of sex chromosomes with homologous regions. The chromosomes of neighboring pairs are partially homologous, such that a chain is formed during mitosis.{{cite journal | vauthors = Grützner F, Rens W, Tsend-Ayush E, El-Mogharbel N, O'Brien PC, Jones RC, Ferguson-Smith MA, Marshall Graves JA | display-authors = 6 | title = In the platypus a meiotic chain of ten sex chromosomes shares genes with the bird Z and mammal X chromosomes | journal = Nature | volume = 432 | issue = 7019 | pages = 913–7 | date = December 2004 | pmid = 15502814 | doi = 10.1038/nature03021 | s2cid = 4379897 | bibcode = 2004Natur.432..913G }} The first X chromosome in the chain is also partially homologous with the last Y chromosome, indicating that profound rearrangements, some adding new pieces from autosomes, have occurred in history.{{cite journal | vauthors = Cortez D, Marin R, Toledo-Flores D, Froidevaux L, Liechti A, Waters PD, Grützner F, Kaessmann H | display-authors = 6 | title = Origins and functional evolution of Y chromosomes across mammals | journal = Nature | volume = 508 | issue = 7497 | pages = 488–493 | date = April 2014 | pmid = 24759410 | doi = 10.1038/nature13151 | s2cid = 4462870 | bibcode = 2014Natur.508..488C }}{{cite journal | vauthors = Deakin JE, Graves JA, Rens W | title = The evolution of marsupial and monotreme chromosomes | journal = Cytogenetic and Genome Research | volume = 137 | issue = 2–4 | pages = 113–129 | date = 2012 | pmid = 22777195 | doi = 10.1159/000339433 | doi-access = free | hdl = 1885/64794 | hdl-access = free }}{{rp|at=fig. 5}}

Platypus sex chromosomes have strong sequence similarity with the avian Z chromosome, indicating close homology,{{cite journal | vauthors = Warren WC, Hillier LW, Marshall Graves JA, Birney E, Ponting CP, Grützner F, Belov K, Miller W, Clarke L, Chinwalla AT, Yang SP, Heger A, Locke DP, Miethke P, Waters PD, Veyrunes F, Fulton L, Fulton B, Graves T, Wallis J, Puente XS, López-Otín C, Ordóñez GR, Eichler EE, Chen L, Cheng Z, Deakin JE, Alsop A, Thompson K, Kirby P, Papenfuss AT, Wakefield MJ, Olender T, Lancet D, Huttley GA, Smit AF, Pask A, Temple-Smith P, Batzer MA, Walker JA, Konkel MK, Harris RS, Whittington CM, Wong ES, Gemmell NJ, Buschiazzo E, Vargas Jentzsch IM, Merkel A, Schmitz J, Zemann A, Churakov G, Kriegs JO, Brosius J, Murchison EP, Sachidanandam R, Smith C, Hannon GJ, Tsend-Ayush E, McMillan D, Attenborough R, Rens W, Ferguson-Smith M, Lefèvre CM, Sharp JA, Nicholas KR, Ray DA, Kube M, Reinhardt R, Pringle TH, Taylor J, Jones RC, Nixon B, Dacheux JL, Niwa H, Sekita Y, Huang X, Stark A, Kheradpour P, Kellis M, Flicek P, Chen Y, Webber C, Hardison R, Nelson J, Hallsworth-Pepin K, Delehaunty K, Markovic C, Minx P, Feng Y, Kremitzki C, Mitreva M, Glasscock J, Wylie T, Wohldmann P, Thiru P, Nhan MN, Pohl CS, Smith SM, Hou S, Nefedov M, de Jong PJ, Renfree MB, Mardis ER, Wilson RK | display-authors = 6 | title = Genome analysis of the platypus reveals unique signatures of evolution | journal = Nature | volume = 453 | issue = 7192 | pages = 175–183 | date = May 2008 | pmid = 18464734 | pmc = 2803040 | doi = 10.1038/nature06936 | bibcode = 2008Natur.453..175W }} and the SRY gene so central to sex-determination in most other mammals is apparently not involved in platypus sex-determination.{{cite journal | vauthors = Veyrunes F, Waters PD, Miethke P, Rens W, McMillan D, Alsop AE, Grützner F, Deakin JE, Whittington CM, Schatzkamer K, Kremitzki CL, Graves T, Ferguson-Smith MA, Warren W, Marshall Graves JA | display-authors = 6 | title = Bird-like sex chromosomes of platypus imply recent origin of mammal sex chromosomes | journal = Genome Research | volume = 18 | issue = 6 | pages = 965–973 | date = June 2008 | pmid = 18463302 | pmc = 2413164 | doi = 10.1101/gr.7101908 }}

{{cleanup section|reason=Too many subsections. Article might benefit from moving h3 subsections into h2 sections, if we can somehow reconcile the gap between all therians and humans. "Origins and evolution" section has a human focus, but the discussion does include all therians.|talksection=Move page to "Human Y Chromosome"|date=October 2021}}

The human Y chromosome is composed of about 62 million base pairs of DNA, making it similar in size to chromosome 19 and represents almost 2% of the total DNA in a male cell.{{cite web |date=February 2014 |title=Ensembl Human MapView release 43 |url=http://www.ensembl.org/Homo_sapiens/mapview?chr=Y |access-date=2007-04-14}}{{cite web |title=National Library of Medicine's Genetic Home Reference |url=http://ghr.nlm.nih.gov/chromosome=Y |url-status=dead |archive-url=https://web.archive.org/web/20120329043034/http://ghr.nlm.nih.gov/chromosome=Y |archive-date=2012-03-29 |access-date=2009-11-09}} The human Y chromosome carries 693 genes, 106 of which are protein-coding.{{cite journal |display-authors=6 |vauthors=Rhie A, Nurk S, Cechova M, Hoyt SJ, Taylor DJ, Altemose N, Hook PW, Koren S, Rautiainen M, Alexandrov IA, Allen J, Asri M, Bzikadze AV, Chen NC, Chin CS, Diekhans M, Flicek P, Formenti G, Fungtammasan A, Garcia Giron C, Garrison E, Gershman A, Gerton JL, Grady PG, Guarracino A, Haggerty L, Halabian R, Hansen NF, Harris R, Hartley GA, Harvey WT, Haukness M, Heinz J, Hourlier T, Hubley RM, Hunt SE, Hwang S, Jain M, Kesharwani RK, Lewis AP, Li H, Logsdon GA, Lucas JK, Makalowski W, Markovic C, Martin FJ, Mc Cartney AM, McCoy RC, McDaniel J, McNulty BM, Medvedev P, Mikheenko A, Munson KM, Murphy TD, Olsen HE, Olson ND, Paulin LF, Porubsky D, Potapova T, Ryabov F, Salzberg SL, Sauria ME, Sedlazeck FJ, Shafin K, Shepelev VA, Shumate A, Storer JM, Surapaneni L, Taravella Oill AM, Thibaud-Nissen F, Timp W, Tomaszkiewicz M, Vollger MR, Walenz BP, Watwood AC, Weissensteiner MH, Wenger AM, Wilson MA, Zarate S, Zhu Y, Zook JM, Eichler EE, O'Neill RJ, Schatz MC, Miga KH, Makova KD, Phillippy AM |date=September 2023 |title=The complete sequence of a human Y chromosome |journal=Nature |volume=621 |issue=7978 |pages=344–354 |bibcode=2023Natur.621..344R |doi=10.1038/s41586-023-06457-y |pmid=37612512 |pmc=10752217 |s2cid=254181409}} However, some genes are repeated, making the number of exclusive protein-coding genes just 42. The Consensus Coding Sequence (CCDS) Project only classifies 63 out of 107 genes.{{cite journal | vauthors = Pertea M, Salzberg SL | title = Between a chicken and a grape: estimating the number of human genes | journal = Genome Biology | volume = 11 | issue = 5 | pages = 206 | date = 2010-05-05 | pmid = 20441615 | pmc = 2898077 | doi = 10.1186/gb-2010-11-5-206 | doi-access = free }}

All single-copy Y-linked genes are hemizygous (present on only one chromosome) except in cases of aneuploidy such as XYY syndrome or XXYY syndrome. Traits that are inherited via the Y chromosome are called Y-linked traits, or holandric traits (from Ancient Greek ὅλος hólos, "whole" + ἀνδρός andrós, "male").{{cite web|url=https://www.dictionary.com/browse/holandric|title=Definition of holandric | work = Dictionary.com| language=en|access-date=2020-01-21}}

At the end of the Human Genome Project (and after many updates) almost half of the Y chromosome remained un-sequenced even in 2021; a different Y chromosome from the HG002 (GM24385) genome was completely sequenced in January 2022 and is included in the new "complete genome" human reference genome sequence, CHM13. The complete sequencing of a human Y chromosome was shown to contain 62,460,029 base pairs and 41 additional genes. This added 30 million base pairs, but it was discovered that the Y chromosome can vary a lot in size between individuals, from 45.2 million to 84.9 million base pairs.{{cite journal | vauthors = Hallast P, Ebert P, Loftus M, Yilmaz F, Audano PA, Logsdon GA, Bonder MJ, Zhou W, Höps W, Kim K, Li C, Hoyt SJ, Dishuck PC, Porubsky D, Tsetsos F, Kwon JY, Zhu Q, Munson KM, Hasenfeld P, Harvey WT, Lewis AP, Kordosky J, Hoekzema K, O'Neill RJ, Korbel JO, Tyler-Smith C, Eichler EE, Shi X, Beck CR, Marschall T, Konkel MK, Lee C | display-authors = 6 | title = Assembly of 43 human Y chromosomes reveals extensive complexity and variation | journal = Nature | volume = 621 | issue = 7978 | pages = 355–364 | date = September 2023 | pmid = 37612510 | doi = 10.1038/s41586-023-06425-6 | pmc = 10726138 | bibcode = 2023Natur.621..355H | s2cid = 261098546 }}

Since almost half of the human Y sequence was unknown before 2022, it could not be screened out as contamination in microbial sequencing projects. As a result, the NCBI RefSeq bacterial genome database mistakenly includes some Y chromosome data.

{{missing information|NRY/MSY structure - How there's a huge chunk of heterochromatin in q, nomenclature of the palindromes and amplicons, TTTY transcripts, etc. Best if we add a figure that mashes together the tops of Colaco 2018 Fig 1 and PMID 12815422 fig 3.|date=October 2021}}

{{multiple image

| header = G-banding ideograms of human Y chromosome

| total_width = 330

| image1 = Human chromosome Y ideogram vertical.svg

| width1 = 216

| height1= 1125

| caption1 = G-banding ideogram of human Y chromosome in resolution 850 bphs. Band length in this diagram is proportional to base-pair length. This type of ideogram is generally used in genome browsers (e.g. Ensembl, UCSC Genome Browser).

| image2 = Human chromosome Y - 400 550 850 bphs.png

| width2 = 1003

| height2= 2801

| caption2 = G-banding patterns of human Y chromosome in three different resolutions (400,{{cite web | work = Genome Decoration Page | publisher = U.S. National Center for Biotechnology Information (NCBI) | url = http://ftp.ncbi.nlm.nih.gov/pub/gdp/ideogram_9606_GCF_000001305.14_400_V1 | title = Ideogram data for Homo sapience (400 bphs, Assembly GRCh38.p3 | date = 2014-06-04 | access-date = 2017-04-26 }}

550{{cite web | work = Genome Decoration Page | publisher = U.S. National Center for Biotechnology Information (NCBI) | url = http://ftp.ncbi.nlm.nih.gov/pub/gdp/ideogram_9606_GCF_000001305.14_550_V1 | title = Ideogram data for Homo sapience (550 bphs, Assembly GRCh38.p3) | date = 2015-08-11 | access-date = 2017-04-26 }} and 850). Band length in this diagram is based on the ideograms from ISCN (2013).{{cite book|author=International Standing Committee on Human Cytogenetic Nomenclature|title=ISCN 2013: An International System for Human Cytogenetic Nomenclature (2013)|url=https://books.google.com/books?id=lGCLrh0DIwEC|year=2013|publisher=Karger Medical and Scientific Publishers|isbn=978-3-318-02253-7}} This type of ideogram represents actual relative band length observed under a microscope at the different moments during the mitotic process.{{cite book| vauthors = Sethakulvichai W, Manitpornsut S, Wiboonrat M, Lilakiatsakun W, Assawamakin A, Tongsima S |title=2012 Ninth International Conference on Computer Science and Software Engineering (JCSSE)|chapter=Estimation of band level resolutions of human chromosome images|year=2012|pages=276–282|doi=10.1109/JCSSE.2012.6261965|url=https://www.researchgate.net/publication/261304470|isbn=978-1-4673-1921-8|s2cid=16666470}}

}}

{{Further|Human Y-chromosome DNA haplogroup}}

The human Y chromosome is normally unable to recombine with the X chromosome, except for small pieces of pseudoautosomal regions (PARs) 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.{{cite web | title = Scientists Reshape Y Chromosome Haplogroup Tree Gaining New Insights Into Human Ancestry | url = https://www.sciencedaily.com/releases/2008/04/080401184955.htm | work = Science Daily | date = 3 April 2008 }} Single-nucleotide polymorphisms (SNPs) in this region are used to trace direct paternal ancestral lines.

More specifically, PAR1 is at 0.1–2.7 Mb. PAR2 is at 56.9–57.2 Mb. The non-recombining region (NRY) or male-specific region (MSY) sits between. Their sizes is now known perfectly from CHM13: 2.77 Mb and 329.5 kb. Until CHM13 the data in PAR1 and PAR2 was just copied over from X chromosome.

Older gene count estimates of human Y chromosome used only partial sequences. Only the T2T sequence (2023) was able to produce a complete sequence of the human Y chromosome.

{{Category see also|Genes on human chromosome Y}}

In general, the human Y chromosome is extremely gene poor—it is one of the largest gene deserts in the human genome. Disregarding pseudoautosomal genes, genes encoded on the human Y chromosome include:

Diseases linked to the Y chromosome typically involve an aneuploidy, an atypical number of chromosomes.

Males can lose the Y chromosome in a subset of cells, known as mosaic loss. Mosaic loss is strongly associated with age,{{cite journal | vauthors = Zeiher A, Braun T | title = Mosaic loss of Y chromosome during aging | journal = Science | volume = 377 | issue = 6603 | pages = 266–7 | date = July 2022 | pmid = 35857599 | doi = 10.1126/science.add0839 | bibcode = 2022Sci...377..266Z | s2cid = 250579530 }} and smoking is another important risk factor for mosaic loss.{{cite journal | vauthors = Forsberg LA | title = Loss of chromosome Y (LOY) in blood cells is associated with increased risk for disease and mortality in aging men | journal = Human Genetics | volume = 136 | issue = 5 | pages = 657–663 | date = May 2017 | pmid = 28424864 | pmc = 5418310 | doi = 10.1007/s00439-017-1799-2 }}

Mosaic loss may be related to health outcomes, indicating that the Y chromosome plays important roles outside of sex determination.{{cite journal | vauthors = Forsberg LA, Rasi C, Malmqvist N, Davies H, Pasupulati S, Pakalapati G, Sandgren J, Diaz de Ståhl T, Zaghlool A, Giedraitis V, Lannfelt L, Score J, Cross NC, Absher D, Janson ET, Lindgren CM, Morris AP, Ingelsson E, Lind L, Dumanski JP | display-authors = 6 | title = Mosaic loss of chromosome Y in peripheral blood is associated with shorter survival and higher risk of cancer | journal = Nature Genetics | volume = 46 | issue = 6 | pages = 624–8 | date = June 2014 | pmid = 24777449 | pmc = 5536222 | doi = 10.1038/ng.2966 }} Males with a higher percentage of hematopoietic stem cells lacking the Y chromosome have a higher risk of certain cancers and have a shorter life expectancy. In many cases, a cause and effect relationship between the Y chromosome and health outcomes has not been determined, and some propose loss of the Y chromosome could be a "neutral karyotype related to normal aging".{{cite journal | vauthors = Guo X, Dai X, Zhou T, Wang H, Ni J, Xue J, Wang X | title = Mosaic loss of human Y chromosome: what, how and why | journal = Human Genetics | volume = 139 | issue = 4 | pages = 421–446 | date = April 2020 | pmid = 32020362 | doi = 10.1007/s00439-020-02114-w | s2cid = 211036885 }} However, a 2022 study showed that mosaic loss of the Y chromosome causally contributes to fibrosis, heart risks, and mortality.{{cite journal | vauthors = Sano S, Horitani K, Ogawa H, Halvardson J, Chavkin NW, Wang Y, Sano M, Mattisson J, Hata A, Danielsson M, Miura-Yura E, Zaghlool A, Evans MA, Fall T, De Hoyos HN, Sundström J, Yura Y, Kour A, Arai Y, Thel MC, Arai Y, Mychaleckyj JC, Hirschi KK, Forsberg LA, Walsh K | display-authors = 6 | title = Hematopoietic loss of Y chromosome leads to cardiac fibrosis and heart failure mortality | journal = Science | volume = 377 | issue = 6603 | pages = 292–7 | date = July 2022 | pmid = 35857592 | pmc = 9437978 | doi = 10.1126/science.abn3100 | bibcode = 2022Sci...377..292S }}

• News article: {{cite news | vauthors = Kolata G |date=14 July 2022 |title=As Y Chromosomes Vanish With Age, Heart Risks May Grow |work=The New York Times |url=https://www.nytimes.com/2022/07/14/health/y-chromosome-heart-failure.html |access-date=21 August 2022}}

Further studies are needed to understand how mosaic Y chromosome loss may contribute to other sex differences in health outcomes, such as how male smokers have between 1.5 and 2 times the risk of non-respiratory cancers as female smokers.{{cite journal | vauthors = Coghlan A |date=13 December 2014 |title=Y men are more likely to get cancer than women |url=https://www.newscientist.com/article/mg22429995.800-y-men-are-more-likely-to-get-cancer-than-women.html |journal=New Scientist |page=17}}{{cite journal | vauthors = Dumanski JP, Rasi C, Lönn M, Davies H, Ingelsson M, Giedraitis V, Lannfelt L, Magnusson PK, Lindgren CM, Morris AP, Cesarini D, Johannesson M, Tiensuu Janson E, Lind L, Pedersen NL, Ingelsson E, Forsberg LA | display-authors = 6 | title = Mutagenesis. Smoking is associated with mosaic loss of chromosome Y | journal = Science | volume = 347 | issue = 6217 | pages = 81–83 | date = January 2015 | pmid = 25477213 | pmc = 4356728 | doi = 10.1126/science.1262092 | bibcode = 2015Sci...347...81D }} Potential countermeasures identified so far include not smoking or stopping smoking and at least one potential drug that "may help counteract the harmful effects of the chromosome loss" is under investigation.{{cite news |title=Loss of male sex chromosome leads to earlier death for men |language=en |work=University of Virginia |url=https://medicalxpress.com/news/2022-07-loss-male-sex-chromosome-earlier.html |access-date=31 August 2022}}{{cite news |date=14 July 2022 |title=Loss of male sex chromosome may lead to earlier death for men – study |language=en |work=The Independent |url=https://www.independent.co.uk/news/science/chromosomes-dna-uva-university-of-virginia-uk-biobank-b2123482.html |access-date=31 August 2022}}{{better source needed|date=August 2022}}

Y chromosome microdeletion (YCM) is a family of genetic disorders caused by missing genes in the Y chromosome. Many affected men exhibit no symptoms and lead normal lives. However, YCM is also known to be present in a significant number of men with reduced fertility or reduced sperm count.{{Citation needed|date=October 2018}}

This results in the person presenting a female phenotype (i.e., is born with female-like genitalia) even though that person possesses an XY karyotype. The lack of the second X results in infertility. In other words, viewed from the opposite direction, the person goes through defeminization but fails to complete masculinization.{{Citation needed|date=October 2018}}

The cause can be seen as an incomplete Y chromosome: the usual karyotype in these cases is 45X, 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 is usually a girl with the features of Turner syndrome or mixed gonadal dysgenesis.

{{main|Klinefelter syndrome}}

Klinefelter 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; it does not seem to be due to direct interference by the extra X with expression of Y genes.{{Citation needed|date=October 2018}}

{{main|XYY syndrome}}

47, XYY syndrome (simply known as 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.{{cite book|title=Thompson & Thompson genetics in medicine.|author=Nussbaum, Robert L.|date=2007|publisher=Saunders/Elsevier|others=McInnes, Roderick R., Willard, Huntington F., Hamosh, Ada., Thompson, Margaret W. (Margaret Wilson), 1920-|isbn=978-1416030805|edition= 7th.|location=Philadelphia|oclc=72774424}}

In 1965 and 1966 Patricia Jacobs and colleagues published a chromosome survey of 315 male patients at

Scotland's only special security hospital for the developmentally disabled,

finding a higher than expected number of patients to have an extra Y chromosome.{{cite journal | vauthors = Jacobs PA, Brunton M, Melville MM, Brittain RP, McClemont WF | title = Aggressive behavior, mental sub-normality and the XYY male | journal = Nature | volume = 208 | issue = 5017 | pages = 1351–2 | date = December 1965 | pmid = 5870205 | doi = 10.1038/2081351a0 | s2cid = 4145850 | bibcode = 1965Natur.208.1351J }} The authors of this study wondered "whether an extra Y chromosome predisposes its carriers to unusually aggressive behaviour", and this conjecture "framed the next fifteen years of research on the human Y chromosome".{{cite book| vauthors = Richardson SS |title=Sex Itself: The Search for Male & Female in the Human Genome|date=2013|publisher=U. of Chicago Press|location=Chicago|isbn=978-0-226-08468-8|page=84}}

Through studies over the next decade, this conjecture was shown to be incorrect: the elevated crime rate of XYY males is due to lower median intelligence and not increased aggression,{{cite journal | vauthors = Witkin HA, Mednick SA, Schulsinger F, Bakkestrom E, Christiansen KO, Goodenough DR, Hirschhorn K, Lundsteen C, Owen DR, Philip J, Rubin DB, Stocking M | display-authors = 6 | title = Criminality in XYY and XXY men | journal = Science | volume = 193 | issue = 4253 | pages = 547–555 | date = August 1976 | pmid = 959813 | doi = 10.1126/science.959813 | bibcode = 1976Sci...193..547W }} and increased height was the only characteristic that could be reliably associated with XYY males.{{cite journal | vauthors = Witkin HA, Goodenough DR, Hirschhorn K | title = XYY men: are they criminally aggressive? | journal = The Sciences | volume = 17 | issue = 6 | pages = 10–13 | date = October 1977 | pmid = 11662398 | doi = 10.1002/j.2326-1951.1977.tb01570.x }} The "criminal karyotype" concept is therefore inaccurate.

There are also XXXY syndrome and XXXXY syndrome.

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

Greater degrees of Y chromosome polysomy (having more than one extra copy of the Y chromosome in every cell, e.g., XYYY) are considerably more rare. The extra genetic material in these cases can lead to skeletal abnormalities, dental abnormalities, decreased IQ, delayed development, and respiratory issues, but the severity features of these conditions are variable.{{cite journal | vauthors = Abedi M, Salmaninejad A, Sakhinia E | title = Rare 48, XYYY syndrome: case report and review of the literature | journal = Clinical Case Reports | volume = 6 | issue = 1 | pages = 179–184 | date = January 2018 | pmid = 29375860 | pmc = 5771943 | doi = 10.1002/ccr3.1311 }}

XX male syndrome occurs due to a genetic 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 is present in a zygote, male gonads develop because of the SRY gene.{{cite web |date=2023-09-12 |title=XX Male Syndrome — an overview |work=Science Direct |url=https://www.sciencedirect.com/topics/medicine-and-dentistry/xx-male-syndrome }}
{{cite encyclopedia | vauthors = Dominguez AA, Reijo Pera RA | veditors = Maloy S, Hughes K |title=Infertility |date=2013-01-01 |url=https://www.sciencedirect.com/science/article/pii/B9780123749840007932 |encyclopedia=Brenner's Encyclopedia of Genetics |edition=2nd |pages=71–74 |access-date=2023-09-12 |publisher=Academic Press |doi=10.1016/B978-0-12-374984-0.00793-2 |isbn=978-0-12-374984-0|url-access=subscription }}

{{Main|Human Y-chromosome DNA haplogroup|Y-chromosomal Adam}}

In human genetic genealogy (the application of genetics to traditional genealogy), use of the information contained in the Y chromosome is of particular interest because, unlike other chromosomes, the Y chromosome is passed exclusively from father to son, on the patrilineal line. Mitochondrial DNA, maternally inherited to both sons and daughters, is used in an analogous way to trace the matrilineal line.{{Citation needed|date=October 2018}}

Research is currently investigating whether male-pattern neural development is a direct consequence of Y-chromosome-related gene expression or an indirect result of Y-chromosome-related androgenic hormone production.{{cite journal | vauthors = Kopsida E, Stergiakouli E, Lynn PM, Wilkinson LS, Davies W | title = The Role of the Y Chromosome in Brain Function | journal = Open Neuroendocrinology Journal | volume = 2 | pages = 20–30 | year = 2009 | pmid = 20396406 | pmc = 2854822 | doi = 10.2174/1876528900902010020 |doi-access=free}}

In 1974, male chromosomes were discovered in fetal cells in the blood circulation of women.{{cite journal | vauthors = Schröder J, Tiilikainen A, De la Chapelle A | title = Fetal leukocytes in the maternal circulation after delivery. I. Cytological aspects | journal = Transplantation | volume = 17 | issue = 4 | pages = 346–354 | date = April 1974 | pmid = 4823382 | doi = 10.1097/00007890-197404000-00003 | s2cid = 35983351 | doi-access = free }}

In 1996, it was found that male fetal progenitor cells could persist postpartum in the maternal blood stream for as long as 27 years.{{cite journal | vauthors = Bianchi DW, Zickwolf GK, Weil GJ, Sylvester S, DeMaria MA | title = Male fetal progenitor cells persist in maternal blood for as long as 27 years postpartum | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 2 | pages = 705–8 | date = January 1996 | pmid = 8570620 | pmc = 40117 | doi = 10.1073/pnas.93.2.705 | doi-access = free | bibcode = 1996PNAS...93..705B }}

A 2004 study at the Fred Hutchinson Cancer Research Center, Seattle, investigated the origin of male chromosomes found in the peripheral blood of women who had not had male progeny. A total of 120 subjects (women who had never had sons) were investigated, and it was found that 21% of them had male DNA in their peripheral blood. The subjects were categorised into four groups based on their case histories:{{cite journal | vauthors = Yan Z, Lambert NC, Guthrie KA, Porter AJ, Loubiere LS, Madeleine MM, Stevens AM, Hermes HM, Nelson JL | display-authors = 6 | title = Male microchimerism in women without sons: quantitative assessment and correlation with pregnancy history | journal = The American Journal of Medicine | volume = 118 | issue = 8 | pages = 899–906 | date = August 2005 | pmid = 16084184 | doi = 10.1016/j.amjmed.2005.03.037 }}

• Group A (8%) had had only female progeny.
• Patients in Group B (22%) had a history of one or more miscarriages.
• Patients Group C (57%) had their pregnancies medically terminated.
• Group D (10%) had never been pregnant before.

The study noted that 10% of the women had never been pregnant before, raising the question of where the Y chromosomes in their blood could have come from. The study suggests that possible reasons for occurrence of male chromosome microchimerism could be one of the following:

• miscarriages,
• pregnancies,
• vanished male twin,
• possibly from sexual intercourse.

A 2012 study at the same institute has detected cells with the Y chromosome in multiple areas of the brains of deceased women.{{cite journal | vauthors = Chan WF, Gurnot C, Montine TJ, Sonnen JA, Guthrie KA, Nelson JL | title = Male microchimerism in the human female brain | journal = PLOS ONE | volume = 7 | issue = 9 | pages = e45592 | date = 26 September 2012 | pmid = 23049819 | pmc = 3458919 | doi = 10.1371/journal.pone.0045592 | doi-access = free | bibcode = 2012PLoSO...745592C }}

• Genealogical DNA test
• Genetic genealogy
• Haplodiploid sex-determination system
• Human Y chromosome DNA haplogroups
• List of Y-STR markers
• Muller's ratchet
• Single nucleotide polymorphism
• Y chromosome Short Tandem Repeat (STR)
• Y linkage
• Y-chromosomal Aaron
• Y-chromosomal Adam
• Y-chromosome haplogroups in populations of the world

{{Clear}}

== References ==

{{reflist}}

{{Commons category|Y chromosomes}}

• [https://www.ncbi.nlm.nih.gov/genome/gdv/browser/genome/?id=GCF_009914755.1 CHM13v2.0 Y chromosome]
• [https://www.ensembl.org/Homo_sapiens/Location/Chromosome?chr=Y;r=Y:1-57227415 Ensembl genome browser]
• [http://www.ornl.gov/sci/techresources/Human_Genome/faq/snps.shtml Human Genome Project Information]—Human Chromosome Y Launchpad
• [https://web.archive.org/web/20050207052351/http://wi.mit.edu/news/ontopic/ychromosome.html On Topic: Y Chromosome]—From the Whitehead Institute for Biomedical Research
• [https://www.nature.com/collections/vmssbdktkr Nature]—focus on the Y chromosome
• [https://www.genome.gov/11007628/2003-release-mechanism-preserves-y-chromosome-gene National Human Genome Research Institute (NHGRI)]—Use of Novel Mechanism Preserves Y chromosome Genes
• [http://www.ysearch.org/ Ysearch.org – Public Y-DNA database] {{Webarchive|url=https://web.archive.org/web/20110104031453/http://www.ysearch.org/ |date=2011-01-04 }}
• [http://ycc.biosci.arizona.edu/ Y chromosome Consortium (YCC)] {{Webarchive|url=https://web.archive.org/web/20170116195823/http://ycc.biosci.arizona.edu/ |date=2017-01-16 }}
• [https://www.npr.org/sections/health-shots/2010/01/human_male_still_a_work_in_pro.html NPR's Human Male: Still A Work In Progress]
• [https://web.archive.org/web/20110708112956/www.cambridgedna.com/genealogy-dna-genetic-genealogy.php Genetic Genealogy: About the use of mtDNA and Y chromosome analysis in ancestry testing]

{{Chromosomes}}

{{Chromosome genetics}}

{{Sex (biology)}}

{{DEFAULTSORT:Y Chromosome}}

Category:Andrology

Category:Chromosomes

Chromosome Y

Category:Male

Category:Sex-determination systems

Category:Sexual dimorphism