Y chromosome: Difference between revisions

| centromere_position = [[Centromere#Acrocentric|Acrocentric]]<ref name="StrachanRead2010">{{cite book| first1 = Tom | last1vauthors = Strachan | first2 = Andrew | last2 =T, Read | name-list-style = vancA |title=Human Molecular Genetics|url=https://books.google.com/books?id=dSwWBAAAQBAJ&pg=PA45|date=2 April 2010|publisher=Garland Science|isbn=978-1-136-84407-2|page=45}}</ref><br />(10.4 Mbp<ref name="850bphs">Genome Decoration Page, NCBI. [http://ftp.ncbi.nlm.nih.gov/pub/gdp/ideogram_9606_GCF_000001305.14_850_V1 Ideogram data for Homo sapience (850 bphs, Assembly GRCh38.p3)]. Last update 2014-06-03. Retrieved 2017-04-26.</ref>)

Many [[ectotherm]]ic [[vertebrates]] have no sex chromosomes.<ref>{{Cite journal |last1 vauthors = Devlin |first1=RobertRH, H. |last2=Nagahama |first2=YoshitakaY |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 |issn=0044-8486}}</ref> If these species have different sexes, sex is determined environmentally rather than genetically. For some species, especially [[reptile]]s, sex depends on the incubation temperature.<ref>{{Citationcite book |last vauthors = Gilbert SF |first=Scott F.chapter |title= Environmental Sex Determination |date=2000 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK9989/ |work title =Developmental Biology. 6th| edition = 6th |access-date=2023-10-19 |publisher=Sinauer Associates |language=en}}</ref> Some vertebrates are [[hermaphrodites]], though hermaphroditic species are most commonly [[hermaphrodite#Sequential hermaphrodites|sequential]], meaning the organism switches sex, producing male or female [[gamete]]s at different points in its life, but never producing both at the same time. This is opposed to [[hermaphrodite#Simultaneous hermaphrodites|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 [[Order (biology)|orders]] of fish.<ref>{{Cite journal |last1 vauthors = Kuwamura |first1=TetsuoT, |last2=Sunobe |first2=TomokiT, |last3=Sakai |first3=YoichiY, |last4=Kadota |first4=TatsuruT, |last5=Sawada |first5=KotaK |date=2020-07-01 |title=Hermaphroditism in fishes: an annotated list of species, phylogeny, and mating system |url=https://doi.org/10.1007/s10228-020-00754-6 |journal=Ichthyological Research |language=en |volume=67 |issue=3 |pages=341–360 |doi=10.1007/s10228-020-00754-6 |s2cid=254168012 |issn=1616-3915}}</ref>

The X and Y chromosomes are thought to have evolved from a pair of identical chromosomes,<ref name="muller">{{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|url=https://zenodo.org/record/1426868 }}</ref><ref name="lahn">{{cite journal | vauthors = Lahn BT, Page DC | title = Four evolutionary strata on the human X chromosome | journal = Science | volume = 286 | issue = 5441 | pages = 964–7964–967 | date = October 1999 | pmid = 10542153 | doi = 10.1126/science.286.5441.964 }}<!--http://www.abc.net.au/science/news/stories/s63100.htm [replaced]--></ref> termed [[autosome]]s, when an ancestral animal developed an allelic variation (a so-called "sex locus") and simply possessing this [[allele]] caused the organism to be male.<ref name="Graves, J.A.M 2006" /> 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 [[chromosomal translocation|translocation]].<ref>{{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 = 219–24219–224 | date = June 2006 | pmid = 16650758 | doi = 10.1016/j.gde.2006.04.007 }}</ref>

Until recently, the X and Y chromosomes were thought to have diverged around 300 million years ago.<ref name="Y-chromosome evolution: emerging in">{{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 = 113–24113–124 | date = February 2013 | pmid = 23329112 | pmc = 4120474 | doi = 10.1038/nrg3366 }}</ref> However, research published in 2008 analyzing the [[platypus]] genome<ref name="Warren" /> suggested that the XY sex-determination system would not have been present more than 166 million years ago, when [[monotreme]]s split from other mammals.<ref name="Veyrunes" /> This re-estimation of the age of the [[theria]]n 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.<ref name="Veyrunes" /> The older estimate was based on erroneous reports that the platypus X chromosomes contained these sequences.<ref name="Grützner" /><ref>{{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 }}</ref>

Most chromosomes [[Homologous recombination|recombine]] during meiosis. However, in males, the X and Y pair in a shared region known as the [[pseudoautosomal region]] (PAR).<ref name=":6">{{Cite web |last=PhD |firstvauthors =Julianna 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}}</ref> The PAR undergoes frequent recombination between the X and Y chromosomes,<ref name=":6" /> but recombination is suppressed in other regions of the Y chromosome.<ref name="Graves, J.A.M 2006" /> These regions contain sex-determining and other male-specific genes.<ref>{{Citecite journal |last vauthors = Peneder |first=PeterP, |last2=Wallner |first2=BarbaraB, |last3=Vogl |first3=ClausC |date=October 2017title |title= Exchange of genetic information between therian X and Y chromosome gametologs in old evolutionary strata |url=https://onlinelibrary.wiley.com/doi/10.1002/ece3.3278 |journal = Ecology and Evolution |language=en |volume = 7 | issue = 20 | pages = 8478–8487 |doi date =10.1002/ece3.3278 October 2017 |issn pmid =2045-7758 29075464 | pmc = 5648654 |pmid doi =29075464 10.1002/ece3.3278 }}</ref> Without this suppression, these genes could be lost from the Y chromosome from recombination and cause issues such as infertility.<ref>{{Cite web |title=Y-chromosomal genes affecting male fertility: A review |url=https://www.veterinaryworld.org/Vol.9/July-2016/18.html |access-date=2023-11-13 |website=www.veterinaryworld.org}}</ref>

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.<ref>{{Citecite journal |last=Brookfield |firstvauthors =John F.Brookfield Y.JF |date=1995-10-01 |title = Human Evolution:evolution. Y-chromosome clues to human ancestry |url=https://www.sciencedirect.com/science/article/pii/S0960982295002247 |journal = Current Biology | volume = 5 | issue = 10 | pages = 1114–1115 | date = October 1995 | pmid = 8548280 | doi = 10.1016/S0960-9822(95)00224-7 |issn=0960-9822}}</ref>

By one estimate, the human Y chromosome has lost 1,393 of its 1,438 original genes over the course of its existence, and [[Extrapolation|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.<ref>{{cite journal | vauthors = Graves JA | title = The degenerate Y chromosome--can conversion save it? | journal = Reproduction, Fertility, and Development | volume = 16 | issue = 5 | pages = 527–34527–534 | year = 2004 | pmid = 15367368 | doi = 10.1071/RD03096 }}</ref> Continued loss of genes at the rate of 4.6 genes per million years 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.<ref name="Graves, J.A.M 2006" /><ref>{{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 = 134–44134–144 | date = February 2009 | pmid = 19142680 | doi = 10.1007/s00239-008-9189-y | s2cid = 24010421 | bibcode = 2009JMolE..68..134G | s2cid = 24010421 }}</ref> [[Comparative genomics|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 (biology)|selection]], and [[genetic drift]].<ref name="Graves, J.A.M 2006">{{cite journal | vauthors = Graves JA | title = Sex chromosome specialization and degeneration in mammals | journal = Cell | volume = 124 | issue = 5 | pages = 901–14901–914 | date = March 2006 | pmid = 16530039 | doi = 10.1016/j.cell.2006.02.024 | s2cid = 8379688 | doi-access = free }}</ref>

With a 30% difference between humans and chimpanzees, the Y chromosome is one of the fastest-evolving parts of the [[human genome]].<ref>{{cite news |last vauthors = Wade |first=Nicholas |name-list-style=vancN |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}}</ref> However, these changes have been limited to non-coding sequences and comparisons of the human and [[Common chimpanzee|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.<ref>{{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 = 100–3100–103 | date = September 2005 | pmid = 16136134 | doi = 10.1038/nature04101 | s2cid = 4418662 | bibcode = 2005Natur.437..100H | s2cid = 4418662 }}</ref> 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.<ref>{{cite web |last vauthors = Hsu |first=Christine |name-list-style=vancC |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 }}</ref> 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 division]]s 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.<ref name="Graves, J.A.M 2006"/> The increased mutation opportunity for the Y chromosome is reported by Graves as a factor 4.8.<ref name="Graves, J.A.M 2006" /> However, her original reference obtains this number for the relative mutation rates in male and female germ lines for the lineage leading to humans.<ref>{{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 = 803–19803–819 | date = December 2005 | pmid = 16341006 | doi = 10.1038/nature04338 | doi-access = free | bibcode = 2005Natur.438..803L | doi-access = free }}</ref>

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.<ref name="Graves, J.A.M 2006"/> 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]].<ref>{{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 = 1563–721563–1572 | date = November 2000 | pmid = 11127901 | pmc = 1692900 | doi = 10.1098/rstb.2000.0717 }}</ref>

They found that human Y chromosome is able to "recombine" with itself, using [[palindrome]] [[base pair]] sequences.<ref name="rozen">{{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 = 873–6873–876 | date = June 2003 | pmid = 12815433 | doi = 10.1038/nature01723 | s2cid = 4323263 | bibcode = 2003Natur.423..873R | s2cid = 4323263 }}</ref> Such a "recombination" is called [[gene conversion]].

In the case of the Y chromosomes, the [[palindrome]]s are not [[noncoding 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.<ref name=":2">{{Citecite journal |last1 vauthors = Rozen |first1=SteveS, |last2=Skaletsky |first2=HelenH, |last3=Marszalek |first3=JanetJD, D. |last4=Minx |first4=PatrickPJ, J. |last5=Cordum |first5=HollandHS, S. |last6=Waterston |first6=RobertRH, H. |last7=Wilson |first7=RichardRK, K. |last8=Page DC |first8=David C.display-authors |date=Jun 20036 | title = Abundant gene conversion between arms of palindromes in human and ape Y chromosomes |url=http://www.nature.com/articles/nature01723 |journal = Nature |language=en |volume = 423 | issue = 6942 | pages = 873–876 | date = June 2003 | pmid = 12815433 | doi = 10.1038/nature01723 |pmid s2cid =12815433 4323263 | bibcode = 2003Natur.423..873R |s2cid=4323263 |issn=0028-0836}}</ref>

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.<ref name="Graves, J.A.M 2006" />{{POV statement|date=September 2016}}{{synthesis inline|date=September 2016}} Several species of [[rodent]] in the sister families [[Muridae]] and [[Cricetidae]] have reached these stages,<ref name="Marchal 2003">{{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 = 3–43-4 | pages = 266–73266–273 | year = 2003 | pmid = 14684993 | doi = 10.1159/000074347 | s2cid = 10526522 }}</ref><ref>{{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 = 333–54333–354 | year = 2009 | pmid = 19630566 | doi = 10.1146/annurev-genom-082908-150105 }}</ref> 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.<ref name="Graves, J.A.M 2006" /><ref>{{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 = 211–21211–221 | year = 2007 | pmid = 18391532 | doi = 10.1159/000104771 | s2cid = 25939138 }}</ref><ref name="Arakawa et al. 2002">{{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 = 1–41-4 | pages = 303–9303–309 | year = 2002 | pmid = 12900579 | doi = 10.1159/000071608 | s2cid = 39633026 }}</ref> ''[[Tokudaia]]'' spp. have relocated some other genes ancestrally present on the Y chromosome to the X chromosome.<ref name="Arakawa et al. 2002" /> Both sexes of ''Tokudaia'' spp. and ''Ellobius lutescens'' have an XO genotype ([[Turner syndrome]]),<ref name="Arakawa et al. 2002"/> whereas all ''Ellobius tancrei'' possess an XX genotype.<ref name="Graves, J.A.M 2006" /> 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.<ref name="Marchal 2003" /><ref>{{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 = 1825–311825–1831 | date = September 2000 | pmid = 11052532 | pmc = 1690748 | doi = 10.1098/rspb.2000.1217 }}</ref><ref>{{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=125–129 |doi=10.1016/j.mambio.2008.03.001 }}</ref>

* 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]].<ref>{{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 = 387–94387–394 | date = April 2001 | pmid = 11520338 | doi = 10.1046/j.1365-2540.2001.00803.x | s2cid = 34489270 | doi-access = free }}</ref>

Modern data cast doubt on this hypothesis.<ref name=":1">{{Citecite journal |last vauthors = Bachtrog D |first=Doris|date=2013| title =Y Y-chromosome evolution: emerging insights into processes of Y -chromosome degeneration | journal = Nature Reviews. Genetics | volume = 14 | issue = 2 | pages = 113–124 |doi date =10.1038/nrg3366 February 2013 |issn pmid =1471-0056 23329112 | pmc = 4120474 |pmid doi =23329112 10.1038/nrg3366 }}</ref> 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.<ref name=":0">{{Citecite journal |last1 vauthors = Hughes|first1=Jennifer F.|last2=JF, Skaletsky|first2=Helen|last3= H, Page DC |first3=David C.|date=2012|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 = 1035–1044 |doi date =10.1002/bies.201200066 December 2012 |issn pmid =1521-1878 23055411 | pmc = 3581811 |pmid doi =23055411 10.1002/bies.201200066 }}</ref>

[[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",<ref name=Hamilton67>{{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 = 477–88477–488 | date = April 1967 | pmid = 6021675 | doi = 10.1126/science.156.3774.477 | bibcode = 1967Sci...156..477H }}</ref> given the condition that males and females cost equal amounts to produce:<!-- this is a better explanation than Fisher's contorted text-->

Other organisms have mirror image sex chromosomes: where the homogeneous sex is the male, said to have two Z chromosomes, and the female is the heterogeneous sex with a Z chromosome and a W chromosome.<ref name=":3">{{Citecite journal |last vauthors = Smith |first=JeramiahJJ, |date=SeptemberVoss 2017SR | title = Bird and Mammalmammal Sexsex-Chromosomechromosome Orthologsorthologs Mapmap to the Samesame Autosomalautosomal Regionregion in a Salamandersalamander (Ambystomaambystoma) | journal = Genetics | volume = 177 | issue = 1 | pages = 607–613 |doi date =10.1534/genetics.107.072033 September 2007 | pmid = 17660573 | pmc = 2013703 | doi = 10.1534/genetics.107.072033 }}</ref> For example, the ZW sex-determination system is found in [[bird]]s, [[snake]]s, and [[butterflies]]; the females have ZW sex chromosomes, and males have ZZ sex chromosomes.<ref name=":3" /><ref>{{Citecite journal |last vauthors = Viana |first=PatrikPF, |date=JulyEzaz 27T, 2020de 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 |page pages = 12499 | date = July 2020 | pmid = 32719365 | pmc = 7385105 | doi = 10.1038/s41598-020-69349-5 |pmid=32719365 |pmc=7385105bibcode |bibcode= 2020NatSR..1012499V }}</ref><ref>{{Citecite journal |last vauthors = Sahara |first=KenK, |date=JanuaryYoshido 2012A, 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 |pmid=22187366 |s2cid = 15130561 | doi-access = free }}</ref>

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.<ref name=Schartl>{{cite journal | vauthors = Schartl M | title = A comparative view on sex determination in medaka | journal = Mechanisms of Development | volume = 121 | issue = 7–87-8 | pages = 639–45639–645 | date = July 2004 | pmid = 15210173 | doi = 10.1016/j.mod.2004.03.001 | s2cid = 17401686 | doi-access = free }}</ref>

Monotremes possess four or five ([[platypus]]) 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]].<ref name="Grützner">{{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 = 913–7913–917 | date = December 2004 | pmid = 15502814 | doi = 10.1038/nature03021 | s2cid = 4379897 | bibcode = 2004Natur.432..913G | s2cid = 4379897 }}</ref> 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.<ref>{{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 = 488–93488–493 | date = April 2014 | pmid = 24759410 | doi = 10.1038/nature13151 | s2cid = 4462870 | bibcode = 2014Natur.508..488C | s2cid = 4462870 }}</ref><ref>{{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 = 2–42-4 | pages = 113–29113–129 | date = 2012 | pmid = 22777195 | doi = 10.1159/000339433 | doi-access = free }}</ref>{{rp|at=fig. 5}}

Platypus sex chromosomes have strong sequence similarity with the avian [[ZW sex-determination system|Z chromosome]], (indicating close [[Sequence homology|homology]]),<ref name="Warren">{{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 = 175–83175–183 | date = May 2008 | pmid = 18464734 | pmc = 2803040 | doi = 10.1038/nature06936 | bibcode = 2008Natur.453..175W }}</ref> and the SRY gene so central to sex-determination in most other mammals is apparently not involved in platypus sex-determination.<ref name="Veyrunes">{{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 = 965–73965–973 | date = June 2008 | pmid = 18463302 | pmc = 2413164 | doi = 10.1101/gr.7101908 }}</ref>

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 (biology)|cell]].<ref name="Chromosome Y">{{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}}</ref><ref>{{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}}</ref> The human Y chromosome carries 693 [[gene]]s, 107 of which are [[protein-coding gene|protein-coding]].<ref name=":4Rhie_2023">{{Cite journal |last1=Rhie |first1=Arang |last2=Nurk |first2=Sergey |last3=Cechova |first3=Monika |last4=Hoyt |first4=Savannah J. |last5=Taylor |first5=Dylan J. |last6=Altemose |first6=Nicolas |last7=Hook |first7=Paul W. |last8=Koren |first8=Sergey |last9=Rautiainen |first9=Mikko |last10=Alexandrov |first10=Ivan A. |last11=Allen |first11=Jamie |last12=Asri |first12=Mobin |last13=Bzikadze |first13=Andrey V. |last14=Chen |first14=Nae-Chyun |last15=Chin |first15=Chen-Shan |date=2022-12-01 |title=The complete sequence of a human Y chromosome |url=https://www.biorxiv.org/content/10.1101/2022.12.01.518724v1 |language=en |pages=2022.12.01.518724 |doi=10.1101/2022.12.01.518724 |s2cid=254181409}}</ref> However, some genes are repeated, making the number of exclusive [[protein-coding gene|protein-coding]] genes just 42.<ref name=":4Rhie_2023" /> The [[Consensus CDS Project|Consensus Coding Sequence (CCDS) Project]] only classifies 63 out of 107 genes, though CCDS estimates are often considered lower bounds due to their conservative classification strategy.<ref>{{Citecite journal |last1 vauthors = Pertea |first1=MihaelaM, |last2=Salzberg SL |first2=Steven L.title |date=2010-05-05 |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 |issn=1474-760X |pmc=2898077 |pmid=20441615 |doi-access = free }}</ref> 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 linkage|Y-linked]] traits, or holandric traits (from [[Ancient Greek]] ὅλος ''hólos'', "whole" + ἀνδρός ''andrós'', "male").<ref>{{Cite web|url=https://www.dictionary.com/browse/holandric|title=Definition of holandric {{!}}| work = Dictionary.com|website=www.dictionary.com| language=en|access-date=2020-01-21}}</ref>

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<!--Q54853746-->) genome was completely sequenced in January 2022 and is included in the new "complete genome" human [[reference genome]] sequence, CHM13.<ref name=":4Rhie_2023" /> The complete [[sequencing]] of a human Y chromosome was shown to contain 62,460,029 base pairs and 41 additional [[gene]]s.<ref name=":4Rhie_2023" /> This added 30 million base pairs,<ref name=":4Rhie_2023" /> 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.<ref name=":5">{{Citecite journal |last1 vauthors = Hallast |first1=PilleP, |last2=Ebert |first2=PeterP, |last3=Loftus |first3=MarkM, |last4=Yilmaz |first4=FeyzaF, |last5=Audano |first5=PeterPA, A. |last6=Logsdon |first6=GlennisGA, A. |last7=Bonder |first7=MarcMJ, Jan |last8=Zhou |first8=WeichenW, |last9=Höps |first9=WolframW, |last10=Kim |first10=KwondoK, |last11=Li |first11=ChongC, |last12=Hoyt |first12=SavannahSJ, Dishuck PC, Porubsky D, Tsetsos F, Kwon JY, Zhu Q, Munson KM, Hasenfeld P, Harvey WT, Lewis AP, Kordosky J., |last13=DishuckHoekzema |first13=PhilipK, O'Neill RJ, Korbel JO, Tyler-Smith C., |last14=PorubskyEichler |first14=DavidEE, |last15=TsetsosShi |first15=FotiosX, Beck CR, Marschall T, Konkel MK, Lee C |date display-authors =September 20236 | title = Assembly of 43 human Y chromosomes reveals extensive complexity and variation |url=https://www.nature.com/articles/s41586-023-06425-6 |journal = Nature |language=en |volume = 621 | issue = 7978 | pages = 355–364 |bibcode date =2023Natur.621..355H September 2023 | pmid = 37612510 | doi = 10.1038/s41586-023-06425-6 |issn=1476-4687 |pmidbibcode =37612510 2023Natur.621..355H | s2cid = 261098546 }}</ref>

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.<ref name=":4Rhie_2023" /><ref name = "Rhie_2023">{{Citecite journal |last vauthors = Rhie |first=ArangA, |last2=Nurk |first2=SergeyS, |last3=Cechova |first3=MonikaM, |last4=Hoyt |first4=SavannahSJ, J. |last5=Taylor |first5=DylanDJ, J. |last6=Altemose |first6=NicolasN, |last7=Hook |first7=PaulPW, W. |last8=Koren |first8=SergeyS, |last9=Rautiainen |first9=MikkoM, |last10=Alexandrov |first10=IvanIA, A. |last11=Allen |first11=JamieJ, |last12=Asri |first12=MobinM, |last13=Bzikadze |first13=AndreyAV, V. |last14=Chen |first14=Nae-ChyunNC, |last15=Chin |first15=ChenCS, 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-ShanNissen 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 display-authors =September 20236 | title = The complete sequence of a human Y chromosome |url=https://www.nature.com/articles/s41586-023-06457-y |journal = Nature |language=en |volume = 621 | issue = 7978 | pages = 344–354 | date = September 2023 | pmid = 37612512 | doi = 10.1038/s41586-023-06457-y |issn=1476-4687}}</ref>

|+Genes on the non-recombining portion of the Y chromosome<ref>{{cite journal |last1 vauthors = Colaco |first1=StacyS, |last2=Modi |first2=DeepakD | title = Genetics of the human Y chromosome and its association with male infertility | journal = Reproductive Biology and Endocrinology |date=17 Februaryvolume 2018= |volume=16 | issue = 1 | pages = 14 | date = February 2018 | pmid = 29454353 | pmc = 5816366 | doi = 10.1186/s12958-018-0330-5 |pmid=29454353 |pmc=5816366 |doi-access = free }}</ref>

|[[PCDH11Y]] || [[PDCH11X]]|| X-transposed region (XTR) from Xq21, one of two genes. Once dubbed "PAR3"<ref name="Veerappa 2013 285–293">{{cite journal | vauthors = Veerappa AM, Padakannaya P, Ramachandra NB | title = Copy number variation-based polymorphism in a new pseudoautosomal region 3 (PAR3) of a human X-chromosome-transposed region (XTR) in the Y chromosome | journal = Functional & Integrative Genomics | volume = 13 | issue = 3 | pages = 285–93285–293 | date = August 2013 | pmid = 23708688 | doi = 10.1007/s10142-013-0323-6 | s2cid = 13443194 }}</ref> but later refuted.<ref>{{cite journal | vauthors = Raudsepp T, Chowdhary BP | title = The Eutherian Pseudoautosomal Region | journal = Cytogenetic and Genome Research | volume = 147 | issue = 2–32-3 | pages = 81–94 | date = 6 January 2016 | pmid = 26730606 | doi = 10.1159/000443157 | doi-access = free }}</ref>

Males can lose the Y chromosome in a subset of cells, known as [[Mosaic (genetics)|mosaic]] loss. Mosaic loss is strongly associated with age,<ref>{{Citecite journal |last vauthors = Zeiher |first=AndreasA, |last2=Braun |first2=ThomasT |date=2022-07-15 |title = Mosaic loss of Y chromosome during aging |url=https://www.science.org/doi/10.1126/science.add0839 |journal = Science |language=en |volume = 377 | issue = 6603 | pages = 266–267 | date = July 2022 | pmid = 35857599 | doi = 10.1126/science.add0839 |issn=0036-8075}}</ref> and smoking is another important risk factor for mosaic loss.<ref name=":7">{{cite journal | vauthors = Forsberg LA |date=May 2017 |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 |pmc=5418310 |pmid=28424864}}</ref>

Mosaic loss may be related to health outcomes, indicating that the Y chromosome plays important roles outside of sex determination.<ref name=":7" /><ref name=":8">{{cite journal |display-authors=6 |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 |date display-authors =June 20146 | 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 =624–8 624–628 | date = June 2014 | pmid = 24777449 | pmc = 5536222 | doi = 10.1038/ng.2966 |pmc=5536222 |pmid=24777449}}</ref> Males with a higher percentage of [[haematopoiesis|hematopoietic]] [[stem cells]] lacking the Y chromosome have a higher risk of certain [[cancer]]s and have a shorter life expectancy.<ref name=":8" /> 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]]".<ref>{{cite journal |last1 vauthors = Guo |first1=XihanX, |last2=Dai |first2=XueqinX, |last3=Zhou |first3=TaoT, |last4=Wang |first4=HanH, |last5=Ni |first5=JuanJ, |last6=Xue |first6=JinglunJ, |last7=Wang |first7=XuX |date=April 2020 |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 |pmid=32020362 |s2cid = 211036885 }}</ref> However, a 2022 study showed that mosaic loss of the Y chromosome causally contributes to [[fibrosis]], [[cardiac dysfunction|heart risks]], and mortality.<ref>{{cite journal |last1 vauthors = Sano |first1=SoichiS, |last2=Horitani |first2=KeitaK, |last3=Ogawa |first3=HayatoH, |last4=Halvardson |first4=JonatanJ, |last5=Chavkin |first5=NicholasNW, W. |last6=Wang |first6=YingY, |last7=Sano |first7=MihoM, |last8=Mattisson |first8=JonasJ, |last9=Hata |first9=AtsushiA, |last10=Danielsson |first10=MarcusM, |last11=Miura-Yura |first11=EmiriE, |last12=Zaghlool |first12=AmmarA, |last13=Evans |first13=MeganMA, A. |last14=Fall |first14=ToveT, |last15=De Hoyos |first15=HenryHN, N.Sundström J, Yura Y, Kour A, Arai Y, Thel MC, Arai Y, Mychaleckyj JC, Hirschi KK, Forsberg LA, Walsh K |date=15 Julydisplay-authors 2022= 6 | title = Hematopoietic loss of Y chromosome leads to cardiac fibrosis and heart failure mortality | journal = Science |language=en |volume = 377 | issue = 6603 | pages=292–297 |bibcode=2022Sci...377..292S |doi=10.1126/science.abn3100292–297 |issn=0036-8075 |pmc=9437978date |pmid=35857592 |last16=SundströmJuly |first16=Johan2022 |last17=Yura |first17=Yoshimitsupmid |last18=Kour |first18=Anupreet35857592 |last19=Arai |first19=Yoheipmc |last20=Thel |first20=Mark C.9437978 |last21=Arai |first21=Yukadoi |last22=Mychaleckyj |first22=Josyf C10.1126/science.abn3100 |last23=Hirschi |first23=Karenbibcode K. |last24=Forsberg |first24=Lars A2022Sci...377..292S |last25=Walsh |first25=Kenneth}}

* News article: {{cite news |last1 vauthors = Kolata |first1=GinaG |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}}</ref>

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.<ref>{{cite journal |last vauthors = Coghlan |first=AndyA |name-list-style=vanc |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}}</ref><ref>{{cite journal |display-authors=6 |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 |date display-authors =January 20156 | title = Mutagenesis. Smoking is associated with mosaic loss of chromosome Y | journal = Science | volume = 347 | issue = 6217 | pages =81–3 81–83 |bibcode date =2015Sci...347...81D January 2015 | pmid = 25477213 | pmc = 4356728 | doi = 10.1126/science.1262092 |pmc=4356728 |pmidbibcode =25477213 2015Sci...347...81D }}</ref> Potential countermeasures identified so far include not smoking or [[Smoking cessation|stopping smoking]] and at least one potential drug that "may help counteract the harmful effects of the chromosome loss" is under investigation.<ref>{{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}}</ref><ref>{{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}}</ref>{{better source needed|date=August 2022}}

finding a higher than expected number of patients to have an extra Y chromosome.<ref name="jacobs-1965">{{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 = 1351–21351–1352 | date = December 1965 | pmid = 5870205 | doi = 10.1038/2081351a0 | s2cid = 4145850 | bibcode = 1965Natur.208.1351J | s2cid = 4145850 }}</ref> 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".<ref name="richardson-sex-itself">{{cite book|last1=Richardson|first1=Sarah S.vauthors |= name-list-style =Richardson vancSS |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}}</ref>

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,<ref name="witkin-1976">{{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 = 547–55547–555 | date = August 1976 | pmid = 959813 | doi = 10.1126/science.959813 | bibcode = 1976Sci...193..547W }}</ref> and increased height was the only characteristic that could be reliably associated with XYY males.<ref name="witkin-1977">{{cite journal | last1vauthors = Witkin |HA, first1Goodenough =DR, HermanHirschhorn A.K | last2title = GoodenoughXYY men: are they criminally aggressive? | first2journal = DonaldThe R.Sciences | last3volume = Hirschhorn17 | first3issue = Kurt 6 | name-list-stylepages = vanc10–13 | date=1977 |title=XYY Men:October Are1977 They| Criminallypmid Aggressive? |journal=The Sciences11662398 |volume=17 |issue=6doi |pages=10–13 |doi=10.1002/j.2326-1951.1977.tb01570.x | pmidname-list-style = 11662398vanc }}</ref> The "criminal karyotype" concept is therefore inaccurate.<ref name="1950- 2007"/>

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.<ref>{{Citecite journal |last1 vauthors = Abedi|first1=Maryam|last2= M, Salmaninejad|first2=Arash|last3= A, Sakhinia E |first3=Ebrahim|date=2017-12-07| title = Rare 48, XYYY syndrome: case report and review of the literature | journal = Clinical Case Reports | volume = 6 | issue = 1 | pages = 179–184 |doi date =10.1002/ccr3.1311 January 2018 |issn pmid =2050-0904 29375860 | pmc = 5771943 |pmid doi =29375860 10.1002/ccr3.1311 }}</ref>

[[XX male syndrome]] occurs due to a [[genetic recombination]] in the formation of the male [[gamete]]s, causing the [[SRY]] portion of the Y chromosome to move to the X chromosome.<ref name="XX male" /> When such an X chromosome is present in a zygote, male gonads develop because of the SRY gene.<ref name="XX male">{{cite web |date=2023-09-12 |title=XX Male Syndrome - an overview {{!}} ScienceDirect Topics |url=https://www.sciencedirect.com/topics/medicine-and-dentistry/xx-male-syndrome#:~:text=XX%20male%20syndrome%20results,development%20occurs. |url-status=dead |archive-date=2023-09-12 |archive-url=https://web.archive.org/web/20230912103457/https://www.sciencedirect.com/topics/medicine-and-dentistry/xx-male-syndrome#:~:text=XX%20male%20syndrome%20results,development%20occurs. |access-date=2023-09-12 |website=Science Direct}}<br>{{cite encyclopedia |last1 vauthors = Dominguez |first1=A.AA, A. |last2=Reijo Pera RA |first2=R. A.veditors |editor2-last= Maloy S, Hughes |editor2-first=KellyK |title=Infertility |date=2013-01-01 |url=https://www.sciencedirect.com/science/article/pii/B9780123749840007932 |encyclopedia=Brenner's Encyclopedia of Genetics (Second Edition) |pages=71–74 |editor-last=Maloy |editor-first=Stanley |access-date=2023-09-12 |place=San Diego |publisher=Academic Press |doi=10.1016/B978-0-12-374984-0.00793-2 |isbn=9780080961569}}</ref>

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.<ref name="Kopsida 2009">{{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 | url = http://www.benthamscience.com/open/toneuroej/articles/V002/20TONEUROEJ.pdf | access-date = 2013-04-05 | archiveurl-datestatus = 2013-10-19dead | archive-url = https://web.archive.org/web/20131019155843/http://www.benthamscience.com/open/toneuroej/articles/V002/20TONEUROEJ.pdf | urlarchive-statusdate = dead2013-10-19 }}</ref>

In 1974, male chromosomes were discovered in fetal cells in the blood circulation of women.<ref name="SchroederEtAl1974">{{cite journal | vauthors = Schröder J, ThlikainenTiilikainen A, deDe la Chapelle A | title = Fetal leukocytes in the maternal circulation after delivery:. I. Cytological aspects | journal = Transplantation | volume = 17 | issue = 4 |year=1974| pages = 346–354 |issn date =0041-1337 April 1974 | pmid = 4823382 | doi = 10.1097/00007890-197404000-00003 |pmid=4823382| s2cid = 35983351 }}</ref>

In 1996, it was found that male fetal progenitor cells could persist postpartum in the maternal blood stream for as long as 27 years.<ref name="BianchiEtAl1996">{{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 = 705–8705–708 | date = January 1996 | pmid = 8570620 | pmc = 40117 | doi = 10.1073/pnas.93.2.705 | doi-access = free | bibcode = 1996PNAS...93..705B | doi-access = free }}</ref>

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. The subjects were categorised into four groups based on their case histories:<ref name="YanEtAl2004">{{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 | url = http://www.amjmed.com/article/S0002-9343(05)00270-6/fulltext | format = full text }}</ref>

A 2012 study at the same institute has detected cells with the Y chromosome in multiple areas of the brains of deceased women.<ref name="ChanEtAl2012">{{cite journal | vauthors = Chan WF, Gurnot C, Montine TJ, Sonnen JA, Guthrie KA, Nelson JL | title = Male microchimerism in the human female brain | journal = PLOSPloS ONEOne | volume = 7 | issue = 9 | pages = e45592 | date = 26 September 2012 | pmid = 23049819 | pmc = 3458919 | doi = 10.1371/journal.pone.0045592 | bibcodedoi-access = 2012PLoSO...745592Cfree | doi-accessbibcode = free2012PLoSO...745592C }}</ref>