The human Y chromosome exhibits surprisingly low levels of genetic diversity. This could result from neutral processes if the effective population size of males is reduced relative to females due to a higher variance in the number of offspring from males than from females. Alternatively, selection acting on new mutations, and affecting linked neutral sites, could reduce variability on the Y chromosome. Here, using genome-wide analyses of X, Y, autosomal and mitochondrial DNA, in combination with extensive population genetic simulations, we show that low observed Y chromosome variability is not consistent with a purely neutral model. Instead, we show that models of purifying selection are consistent with observed Y diversity. Further, the number of sites estimated to be under purifying selection greatly exceeds the number of Y-linked coding sites, suggesting the importance of the highly repetitive ampliconic regions. While we show that purifying selection removing deleterious mutations can explain the low diversity on the Y chromosome, we cannot exclude the possibility that positive selection acting on beneficial mutations could have also reduced diversity in linked neutral regions, and may have contributed to lowering human Y chromosome diversity. Because the functional significance of the ampliconic regions is poorly understood, our findings should motivate future research in this area.
Vyšlo v časopise: Natural Selection Reduced Diversity on Human Y Chromosomes. PLoS Genet 10(1): e32767. doi:10.1371/journal.pgen.1004064 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004064
1. JoblingMA, Tyler-SmithC (2003) The human Y chromosome: an evolutionary marker comes of age. Nat Rev Genet 4 : 598–612.
2. JoblingMA (2012) The impact of recent events on human genetic diversity. Philos Trans R Soc Lond B Biol Sci 367 : 793–799.
3. KeinanA, MullikinJC, PattersonN, ReichD (2009) Accelerated genetic drift on chromosome X during the human dispersal out of Africa. Nat Genet 41 : 66–70.
4. HammerMF, MendezFL, CoxMP, WoernerAE, WallJD (2008) Sex-biased evolutionary forces shape genomic patterns of human diversity. PLoS Genetics 4: e1000202.
5. GottipatiS, ArbizaL, SiepelA, ClarkAG, KeinanA (2011) Analyses of X-linked and autosomal genetic variation in population-scale whole genome sequencing. Nature Genetics 43 : 741–743.
6. CaballeroA (1995) On the Effective Size of Populations with Separate Sexes, with Particular Reference to Sex-Linked Genes. Genetics 139 : 1007–1011.
7. Helena MangsA, MorrisBJ (2007) The Human Pseudoautosomal Region (PAR): Origin, Function and Future. Curr Genomics 8 : 129–136.
8. AguadeM, MiyashitaN, LangleyCH (1989) Reduced variation in the yellow-achaete-scute region in natural populations of Drosophila melanogaster. Genetics 122 : 607–615.
9. BegunDJ, AquadroCF (1992) Levels of naturally occurring DNA polymorphism correlate with recombination rates in D. melanogaster. Nature 356 : 519–520.
10. StephanW, LangleyCH (1989) Molecular genetic variation in the centromeric region of the X chromosome in three Drosophila ananassae populations. I. Contrasts between the vermilion and forked loci. Genetics 121 : 89–99.
11. MoghadamHK, PointerMA, WrightAE, BerlinS, MankJE (2012) W chromosome expression responds to female-specific selection. Proc Natl Acad Sci U S A 109 : 8207–8211.
12. RozenS, MarszalekJD, AlagappanRK, SkaletskyH, PageDC (2009) Remarkably little variation in proteins encoded by the Y chromosome's single-copy genes, implying effective purifying selection. Am J Hum Genet 85 : 923–928.
13. WilderJA, MobasherZ, HammerMF (2004) Genetic evidence for unequal effective population sizes of human females and males. Mol Biol Evol 21 : 2047–2057.
14. WhitfieldLS, SulstonJE, GoodfellowPN (1995) Sequence variation of the human Y chromosome. Nature 378 : 379–380.
15. PritchardJK, SeielstadMT, Perez-LezaunA, FeldmanMW (1999) Population growth of human Y chromosomes: a study of Y chromosome microsatellites. Mol Biol Evol 16 : 1791–1798.
16. MalaspinaP, PersichettiF, NovellettoA, IodiceC, TerrenatoL, et al. (1990) The human Y chromosome shows a low level of DNA polymorphism. Ann Hum Genet 54 : 297–305.
17. HammerMF, WoernerAE, MendezFL, WatkinsJC, CoxMP, et al. (2010) The ratio of human X chromosome to autosome diversity is positively correlated with genetic distance from genes. Nature Genetics 42 : 830–831.
18. EmeryLS, FelsensteinJ, AkeyJM (2010) Estimators of the human effective sex ratio detect sex biases on different timescales. American Journal of Human Genetics 87 : 848–856.
19. LabudaD, LefebvreJF, NadeauP, Roy-GagnonMH (2010) Female-to-male breeding ratio in modern humans-an analysis based on historical recombinations. American Journal of Human Genetics 86 : 353–363.
20. LohmuellerKE, DegenhardtJD, KeinanA (2010) Sex-averaged recombination and mutation rates on the X chromosome: a comment on Labuda et al. American Journal of Human Genetics 86 : 978–980.
21. CharlesworthB, MorganMT, CharlesworthD (1993) The effect of deleterious mutations on neutral molecular variation. Genetics 134 : 1289–1303.
22. HudsonRR, KaplanNL (1995) Deleterious background selection with recombination. Genetics 141 : 1605–1617.
23. CharlesworthB, CharlesworthD (2000) The degeneration of Y chromosomes. Philosophical Transactions of the Royal Society Biological Sciences 355 : 1563–1572.
24. CharlesworthB (2012) The role of background selection in shaping patterns of molecular evolution and variation: evidence from variability on the Drosophila X chromosome. Genetics 191 : 233–246.
25. McVeanGA, CharlesworthB (2000) The effects of Hill-Robertson interference between weakly selected mutations on patterns of molecular evolution and variation. Genetics 155 : 929–944.
26. KaiserVB, CharlesworthB (2009) The effects of deleterious mutations on evolution in non-recombining genomes. Trends in Genetics 25 : 9–12.
27. SkaletskyH, Kuroda-KawaguchiT, MinxPJ, CordumHS, HillierL, et al. (2003) The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature 423 : 825–837.
28. HughesJF, SkaletskyH, PyntikovaT, GravesTA, van DaalenSK, et al. (2010) Chimpanzee and human Y chromosomes are remarkably divergent in structure and gene content. Nature 463 : 536–539.
29. MaraisGA, CamposPR, GordoI (2010) Can intra-Y gene conversion oppose the degeneration of the human Y chromosome? A simulation study. Genome Biology and Evolution 2 : 347–357.
30. MakovaKD, LiWH (2002) Strong male-driven evolution of DNA sequences in humans and apes. Nature 416 : 624–626.
31. JordeLB, WatkinsWS, BamshadMJ, DixonME, RickerCE, et al. (2000) The distribution of human genetic diversity: a comparison of mitochondrial, autosomal, and Y-chromosome data. Am J Hum Genet 66 : 979–988.
32. WilderJA, KinganSB, MobasherZ, PilkingtonMM, HammerMF (2004) Global patterns of human mitochondrial DNA and Y-chromosome structure are not influenced by higher migration rates of females versus males. Nat Genet 36 : 1122–1125.
33. HammerMF, KarafetTM, ReddAJ, JarjanaziH, Santachiara-BenerecettiS, et al. (2001) Hierarchical patterns of global human Y-chromosome diversity. Mol Biol Evol 18 : 1189–1203.
34. WilderJA, MobasherZ, HammerMF (2004) Genetic evidence for unequal effective population sizes of human females and males. Mol Biol Evol 21 : 2047–2057.
35. PoznikGD, HennBM, YeeMC, SliwerskaE, EuskirchenGM, et al. (2013) Sequencing Y chromosomes resolves discrepancy in time to common ancestor of males versus females. Science 341 : 562–565.
36. MendezFL, KrahnT, SchrackB, KrahnAM, VeeramahKR, et al. (2013) An african american paternal lineage adds an extremely ancient root to the human y chromosome phylogenetic tree. Am J Hum Genet 92 : 454–459.
37. BoykoAR, WilliamsonSH, IndapAR, DegenhardtJD, HernandezRD, et al. (2008) Assessing the evolutionary impact of amino acid mutations in the human genome. PLoS Genetics 4: e1000083.
38. AkashiH, OsadaN, OhtaT (2012) Weak selection and protein evolution. Genetics 192 : 15–31.
39. CharlesworthD, CharlesworthB, MorganMT (1995) The pattern of neutral molecular variation under the background selection model. Genetics 141 : 1619–1632.
40. HudsonRR, KaplanNL (1995) The coalescent process and background selection. Philosophical transactions of the Royal Society of LondonSeries B, Biological sciences 349 : 19–23.
41. NordborgM, CharlesworthB, CharlesworthD (1996) The effect of recombination on background selection. Genetical Research 67 : 159–174.
42. StewartJB, FreyerC, ElsonJL, LarssonNG (2008) Purifying selection of mtDNA and its implications for understanding evolution and mitochondrial disease. Nat Rev Genet 9 : 657–662.
43. FujitaPA, RheadB, ZweigAS, HinrichsAS, KarolchikD, et al. (2011) The UCSC Genome Browser database: update 2011. Nucleic Acids Research 39: D876–882.
44. HernandezRD, KelleyJL, ElyashivE, MeltonSC, AutonA, et al. (2011) Classic selective sweeps were rare in recent human evolution. Science 331 : 920–924.
45. LohmuellerKE, AlbrechtsenA, LiY, KimSY, KorneliussenT, et al. (2011) Natural selection affects multiple aspects of genetic variation at putatively neutral sites across the human genome. PLoS Genet 7: e1002326.
46. ReedFA, AkeyJM, AquadroCF (2005) Fitting background-selection predictions to levels of nucleotide variation and divergence along the human autosomes. Genome Res 15 : 1211–1221.
47. McVickerG, GordonD, DavisC, GreenP (2009) Widespread genomic signatures of natural selection in hominid evolution. PLoS Genet 5: e1000471.
48. KaplanNL, HudsonRR, LangleyCH (1989) The “hitchhiking effect” revisited. Genetics 123 : 887–899.
49. Maynard SmithJ, HaighJ (1974) The hitch-hiking effect of a favourable gene. Genet Res 23 : 23–35.
50. FelsensteinJ (1995) PHYLIP - Phylogeny Inference Package (version 3.2). Cladistics 5 : 164–166.
51. YangZ (2007) PAML 4: Phylogenetic analysis by maximum likelihood. Molecular Biology and Evolution 24 : 1586–1591.
52. ChiaroniJ, UnderhillPA, Cavalli-SforzaLL (2009) Y chromosome diversity, human expansion, drift, and cultural evolution. Proc Natl Acad Sci U S A 106 : 20174–20179.
53. WilsonMA, MakovaKD (2009) Evolution and survival on eutherian sex chromosomes. PLoS Genet 5: e1000568.
54. GotoH, PengL, MakovaKD (2009) Evolution of X-degenerate Y chromosome genes in greater apes: conservation of gene content in human and gorilla, but not chimpanzee. J Mol Evol 68 : 134–144.
55. HughesJF, SkaletskyH, BrownLG, PyntikovaT, GravesT, et al. (2012) Strict evolutionary conservation followed rapid gene loss on human and rhesus Y chromosomes. Nature 483 : 82–86.
56. HughesJF, SkaletskyH, PyntikovaT, MinxPJ, GravesT, et al. (2005) Conservation of Y-linked genes during human evolution revealed by comparative sequencing in chimpanzee. Nature 437 : 101–104.
57. DrmanacR, SparksAB, CallowMJ, HalpernAL, BurnsNL, et al. (2009) Human genome sequencing using unchained base reads on self-assembling DNA nanoarrays. Science 327 : 78–81.
58. PoolJE, HellmannI, JensenJD, NielsenR (2010) Population genetic inference from genomic sequence variation. Genome Res 20 : 291–300.
59. BlankenbergD, Von KusterG, CoraorN, AnandaG, LazarusR, et al. (2011) Galaxy: a web-based genome analysis tool for experimentalists. Curr Protoc Mol Biol Chapter 19 : 1–21.
60. StonekingM (2000) Hypervariable sites in the mtDNA control region are mutational hotspots. Am J Hum Genet 67 : 1029–1032.
61. WeiW, AyubQ, ChenY, McCarthyS, HouY, et al. (2013) A calibrated human Y-chromosomal phylogeny based on resequencing. Genome Res 23 : 388–395.
62. IngmanM, KaessmannH, PaaboS, GyllenstenU (2000) Mitochondrial genome variation and the origin of modern humans. Nature 408 : 708–713.
63. HudsonRR (2002) Generating samples under a Wright-Fisher neutral model of genetic variation. Bioinformatics 18 : 337–338.
64. HernandezRD (2008) A flexible forward simulator for populations subject to selection and demography. Bioinformatics 24 : 2786–2787.
65. LohmuellerKE, BustamanteCD, ClarkAG (2009) Methods for human demographic inference using haplotype patterns from genomewide single-nucleotide polymorphism data. Genetics 182 : 217–231.
66. LohmuellerKE, BustamanteCD, ClarkAG (2010) The effect of recent admixture on inference of ancient human population history. Genetics 185 : 611–622.
67. Hartl DL, Clark AG (2006) Principles of Population Genetics. Sunderland, MA: Sinauer Associates.
68. Eyre-WalkerA, KeightleyPD (2009) Estimating the rate of adaptive molecular evolution in the presence of slightly deleterious mutations and population size change. Molecular Biology and Evolution 26 : 2097–2108.
69. Eyre-WalkerA, WoolfitM, PhelpsT (2006) The distribution of fitness effects of new deleterious amino acid mutations in humans. Genetics 173 : 891–900.
70. WilsonMA, MakovaKD (2009) Evolution and survival on eutherian sex chromosomes. PLoS Genetics 5: e1000568.
71. WeissG, von HaeselerA (1998) Inference of population history using a likelihood approach. Genetics 149 : 1539–1546.
72. WallJD (2000) A comparison of estimators of the population recombination rate. Molecular Biology and Evolution 17 : 156–163.
73. Wakeley J (2009) Coalescent Theory. Greenwood Village, CO: Roberts & Company.
74. WilliamsonS, OriveME (2002) The genealogy of a sequence subject to purifying selection at multiple sites. Mol Biol Evol 19 : 1376–1384.
75. PembertonTJ, WangC, LiJZ, RosenbergNA (2010) Inference of unexpected genetic relatedness among individuals in HapMap Phase III. American Journal of Human Genetics 87 : 457–464.
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