Evolutionary dynamics of the human pseudoautosomal regions

English version

Autoři: Bruno Monteiro ^aff001; Miguel Arenas ^aff003; Maria Joao Prata ^aff001; António Amorim ^aff001
Působiště autorů: Institute of Investigation and Innovation in Health (i3S). University of Porto, Porto, Portugal ^aff001; Institute of Molecular Pathology and Immunology (IPATIMUP), University of Porto, Porto, Portugal ^aff002; Department of Biochemistry, Genetics and Immunology, University of Vigo, Vigo, Spain ^aff003; CINBIO (Biomedical Research Centre), University of Vigo, Vigo, Spain ^aff004; Faculty of Sciences, University of Porto, Porto, Portugal ^aff005
Vyšlo v časopise: Evolutionary dynamics of the human pseudoautosomal regions. PLoS Genet 17(4): e1009532. doi:10.1371/journal.pgen.1009532
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1009532

Souhrn

Recombination between the X and Y human sex chromosomes is limited to the two pseudoautosomal regions (PARs) that present quite distinct evolutionary origins. Despite the crucial importance for male meiosis, genetic diversity patterns and evolutionary dynamics of these regions are poorly understood. In the present study, we analyzed and compared the genetic diversity of the PAR regions using publicly available genomic sequences encompassing both PAR1 and PAR2. Comparisons were performed through allele diversities, linkage disequilibrium status and recombination frequencies within and between X and Y chromosomes. In agreement with previous studies, we confirmed the role of PAR1 as a male-specific recombination hotspot, but also observed similar characteristic patterns of diversity in both regions although male recombination occurs at PAR2 to a much lower extent (at least one recombination event at PAR1 and in ≈1% in normal male meioses at PAR2). Furthermore, we demonstrate that both PARs harbor significantly different allele frequencies between X and Y chromosomes, which could support that recombination is not sufficient to homogenize the pseudoautosomal gene pool or is counterbalanced by other evolutionary forces. Nevertheless, the observed patterns of diversity are not entirely explainable by sexually antagonistic selection. A better understanding of such processes requires new data from intergenerational transmission studies of PARs, which would be decisive on the elucidation of PARs evolution and their role in male-driven heterosomal aneuploidies.

Klíčová slova:

Alleles – DNA recombination – Evolutionary genetics – Homologous recombination – Linkage disequilibrium – Meiosis – Sex chromosomes – Y chromosomes

Zdroje

1. Matveevsky S, Kolomiets O, Bogdanovet A, Hakhverdyan M, Bakloushinskaya I. Chromosomal Evolution in Mole Voles Ellobius (Cricetidae, Rodentia): Bizarre Sex Chromosomes, Variable Autosomes and Meiosis. Genes (Basel). 2017;8 : 306. doi: 10.3390/genes8110306 29099806

2. Zhou Y, Shearwin-Whyatt L, Li J, Song Z, Hayakawa T, Stevens D, et al. Platypus and echidna genomes reveal mammalian biology and evolution. Nature. 2021; Forthcoming. doi: 10.1038/s41586-020-03039-0 33408411

3. Cortez D, Marin R, Toledo-Flores D, Froidevaux L, Liechti A, Waters P, et al. Origins and functional evolution of Y chromosomes across mammals. Nature. 2014;508 : 488–493. doi: 10.1038/nature13151 24759410

4. Otto SP, Pannell JR, Peichel CL, Ashman TL, Charlesworth D, Chippindale AK, et al. About PAR: the distinct evolutionary dynamics of the pseudoautosomal region. Trends Genet. 2011;27 : 358–367. doi: 10.1016/j.tig.2011.05.001 21962971

5. Charlesworth B. The evolution of sex chromosomes. Science. 1991;251 : 1030–1033. doi: 10.1126/science.1998119 1998119

6. Furman BLS, Metzger DCH, Darolti J, Wright AE, Sandkam BA, Almeida P, et al. Sex Chromosome Evolution: So Many Exceptions to the Rules. Genome Biol Evol. 2020;12 : 750–763.

7. Kauppi L, Jasin M, Keeney S. The tricky path to recombining X and Y chromosomes in meiosis. Ann N Y Acad Sci. 2012;1267 : 18–23. doi: 10.1111/j.1749-6632.2012.06593.x 22954211

8. Charchar FJ, Svartman M, El-Mogharber N, Ventura M, Kirby P, Matarazzo MR, et al. Complex events in the evolution of the human pseudoautosomal region 2 (PAR2). Genome Res. 2003;13 : 281–286. doi: 10.1101/gr.390503 12566406

9. Freije D, Helms C, Watson MS, Donis-Keller H. Identification of a second pseudoautosomal region near the Xq and Yq telomeres. Science. 1992;258 : 1784–1787. doi: 10.1126/science.1465614 1465614

10. Graves JA, Wakefield MJ, Toder R. The origin and evolution of the pseudoautosomal regions of human sex chromosomes. Hum Mol Genet. 1998;7 : 1991–1996. doi: 10.1093/hmg/7.13.1991 9817914

11. Mangs AH, Morris BJ. The Human Pseudoautosomal Region (PAR): Origin, Function and Future. Curr Genomics. 2007;8 : 129–136. doi: 10.2174/138920207780368141 18660847

12. Charlesworth B. The evolution of chromosomal sex determination. Novartis Found Symp. 2002;244 : 207–219. 11990792

13. Visootsak J, Graham JM Jr. Klinefelter syndrome and other sex chromosomal aneuploidies. Orphanet J Rare Dis. 2006;1 : 42. doi: 10.1186/1750-1172-1-42 17062147

14. Hinch AG, Altemose N, Noor N, Donnely P, Myers SR. Recombination in the human Pseudoautosomal region PAR1. PLoS Genet. 2014;10: e1004503. doi: 10.1371/journal.pgen.1004503 25033397

15. Flaquer A, Fischer C, Wienker TF. A new sex-specific genetic map of the human pseudoautosomal regions (PAR1 and PAR2). Hum Hered. 2009;68 : 192–200. doi: 10.1159/000224639 19521101

16. Flaquer A, Rappold GA, Wienker TF, Fischer C. The human pseudoautosomal regions: a review for genetic epidemiologists. Eur J Hum Genet. 2008;16 : 771–779. doi: 10.1038/ejhg.2008.63 18398439

17. Otto SP. Selective maintenance of recombination between the sex chromosomes. J Evol Biol. 2014;27 : 1431–1442. doi: 10.1111/jeb.12324 24529284

18. Lucotte EA, Laurent R, Heyer E, Ségurel L, Toupance B. Detection of Allelic Frequency Differences between the Sexes in Humans: A Signature of Sexually Antagonistic Selection. Genome Biol Evol. 2016;8 : 1489–1500. doi: 10.1093/gbe/evw090 27189992

19. Gottipati S, Arbiza L, Siepel A, Clark AG, Keinan A. Analyses of X-linked and autosomal genetic variation in population-scale whole genome sequencing. Nat Genet. 2011;43 : 741–743. doi: 10.1038/ng.877 21775991

20. Bergero R, Gardner J, Bader B, Yong L, Charlesworth D. Exaggerated heterochiasmy in a fish with sex-linked male coloration polymorphisms. Proc Natl Acad Sci U S A. 2019; 116(14): 6924–6931. doi: 10.1073/pnas.1818486116 30894479

21. Möller M, Lee YQ, Vidovic K, Kjellstrom S, Bjorkman L, Storry JR, et al. Disruption of a GATA1-binding motif upstream of XG/PBDX abolishes Xga expression and resolves the Xg blood group system. Blood. 2018;132 : 334–338. doi: 10.1182/blood-2018-03-842542 29748255

22. May CA, Shone AC, Kalaydjieva L, Sajantila A, Jeffreys AJ. Crossover clustering and rapid decay of linkage disequilibrium in the Xp/Yp pseudoautosomal gene SHOX. Nat Genet. 2002;31 : 272–275. doi: 10.1038/ng918 12089524

23. Cotter DJ, Brotman SM, Sayres MAY. Genetic Diversity on the Human X Chromosome Does Not Support a Strict Pseudoautosomal Boundary. Genetics. 2016;203 : 485–492. doi: 10.1534/genetics.114.172692 27010023

24. Posada D, Grandall KA. Evaluation of methods for detecting recombination from DNA sequences: Computer simulations. Proc Natl Acad Sci U S A. 2001;98 : 13757–13762. doi: 10.1073/pnas.241370698 11717435

25. Lopes JS, Arenas M, Posada D, Beaumont MA. Coestimation of recombination, substitution and molecular adaptation rates by approximate Bayesian computation. Heredity. 2014;112 : 255–264. doi: 10.1038/hdy.2013.101 24149652

26. Jordan IK, Rishishwar L, Conley AB. Native American admixture recapitulates population-specific migration and settlement of the continental United States. PLOS Genet. 2019;15: e1008225. doi: 10.1371/journal.pgen.1008225 31545791

27. Sarbana S, Denniff M, Jeffreys AJ, Neumann R, Artigas MS, Veselis A, et al. A major recombination hotspot in the XqYq pseudoautosomal region gives new insight into processing of human gene conversion events. Hum Mol Genet. 2012;21 : 2029–2038. doi: 10.1093/hmg/dds019 22291443

28. Stumpf M, McVean G. Estimating recombination rates from population-genetic data. Nat Rev Genet. 2003;4 : 959–968. doi: 10.1038/nrg1227 14631356

29. Jeffreys AJ, Kauppi L, Neumann R. Intensely punctate meiotic recombination in the class II region of the major histocompatibility complex. Nat Genet. 2001;29 : 217–222. doi: 10.1038/ng1001-217 11586303

30. Tiemann-Boege I, Calabrese P, Cochran DM, Sokol R, Arnheim N. High-resolution recombination patterns in a region of human chromosome 21 measured by sperm typing. PLoS Genet. 2006;2: e70. doi: 10.1371/journal.pgen.0020070 16680198

31. Jeffreys AJ, Neumann R, Panayi M, Myers S, Donnelly P. Human recombination hot spots hidden in regions of strong marker association. Nat Genet. 2005;37 : 601–606. doi: 10.1038/ng1565 15880103

32. Kauppi L, Jeffreys AJ, Keeney S. Where the crossovers are: Recombination distributions in mammals. Nat Rev Genet. 2004;5 : 413–424. doi: 10.1038/nrg1346 15153994

33. Lien S, Szyda J, Schechinger B, Rappold G, Arnheim N. Evidence for heterogeneity in recombination in the human pseudoautosomal region: high resolution analysis by sperm typing and radiation-hybrid mapping. Am J Hum Genet. 2000;66 : 557–566. doi: 10.1086/302754 10677316

34. Schmitt K, Vollrath D, Foote S, Fisher EM, Page DC, Arnheim N. Four PCR-based polymorphisms in the pseudoautosomal region of the human X and Y chromosomes. Hum Mol Genet. 1993;2 : 1978. doi: 10.1093/hmg/2.11.1978 8281166

35. Consortium IH. A haplotype map of the human genome. Nature. 2005;437 : 1299–1320. doi: 10.1038/nature04226 16255080

36. Henke A, Fischer C, Rappold GA. Genetic map of the human pseudoautosomal region reveals a high rate of recombination in female meiosis at the Xp telomere. Genomics. 1993;18 : 478–485. doi: 10.1016/s0888-7543(11)80003-0 8307556

37. Vergnaud G. No increase in female recombination frequency in the distal part of the pseudoautosomal region. Genomics. 1994;24 : 610–612. doi: 10.1006/geno.1994.1678 7713521

38. Rouyer F, Simmler M-C, Vergnaud G, Johnsson C, Levilliers J, Petit C, et al. The pseudoautosomal region of the human sex chromosomes. Cold Spring Harb Symp. Quant Biol. 1986;51 : 221–228. doi: 10.1101/sqb.1986.051.01.027 3472718

39. Matise TC, Chen F, Chen W, De La Vega FM, Hansen M, He C, et al. A second-generation combined linkage physical map of the human genome. Genome Res. 2007;A: 1783–1786. doi: 10.1101/gr.7156307 17989245

40. Poriswanish N, Neumann R, Wetton JH, Wagstaff J, Larmuseau MHD, Jobling MA, et al. Recombination hotspots in an extended human pseudoautosomal domain predicted from double-strand break maps and characterized by sperm-based crossover analysis. PLOS Genet. 2018;14: e1007680. doi: 10.1371/journal.pgen.1007680 30296256

41. Jeffreys AJ, Holloway JK, Kauppi L, May CA, Neumann R, Slingsby MT, et al. Meiotic recombination hot spots and human DNA diversity. Philos Trans R Soc Lond B Biol Sci. 2004;359 : 141–152. doi: 10.1098/rstb.2003.1372 15065666

42. Fukami M, Fujisawa Y, Ono H, Jinno T, Ogata T. Human Spermatogenesis Tolerates Massive Size Reduction of the Pseudoautosomal Region. Genome Biol Evol. 2020; 12 : 1961–1964. doi: 10.1093/gbe/evaa168 32785664

43. Bachtrog D, Kirkpatrick M, Mank JE, McDaniel SF, Pires JC, Rice W, Valenzuela N. Are all sex chromosomes created equal? Trends Genet. 2011; 27 : 350–357. doi: 10.1016/j.tig.2011.05.005 21962970

44. Gil-Fernández A, Saunders PA, Martín-Ruiz M, Ribagorda M, López-Jiménez P, Jeffries DL, et al. Meiosis reveals the early steps in the evolution of a neo-XY sex chromosome pair in the African pygmy mouse Mus minutoides. PLoS Genet. 2020;16: e1008959. doi: 10.1371/journal.pgen.1008959 33180767

45. Grossen C, Neuenschwander S, Perrin N. The evolution of XY recombination: sexually antagonistic selection versus deleterious mutation load. Evolution. 2012; 66 : 3155–3166. doi: 10.1111/j.1558-5646.2012.01661.x 23025605

46. Charlesworth B, Jordan CY, Charlesworth D. The evolutionary dynamics of sexually antagonistic mutations in pseudoautosomal regions of sex chromosomes. Evolution. 2014;68 : 1339–1350. doi: 10.1111/evo.12364 24476564

47. Kirkpatrick M, Guerrero RF. Signatures of sex-antagonistic selection on recombining sex chromosomes. Genetics. 2014;197 : 531–541. doi: 10.1534/genetics.113.156026 24578352

48. Dufresnes C, Brelsford A, Baier F, Perrin N. When Sex Chromosomes Recombine Only in the Heterogametic Sex: Heterochiasmy and Heterogamety in Hyla Tree Frogs. Mol Biol Evol. 2021;38 : 192–200. doi: 10.1093/molbev/msaa201 32761205

49. Bissegger M, Laurentino TG, Roesti M, Berner D. Widespread intersex differentiation across the stickleback genome–The signature of sexually antagonistic selection? Mol Ecol. 2020;29 : 262–271. doi: 10.1111/mec.15255 31574563

50. Ruzick F, Dutoit L, Czuppon P, Jordan CY, Li XY, Olito C, et al. The search for sexually antagonistic genes: Practical insights from studies of local adaptation and statistical genomics. Evolution Letters. 2020;4 : 398–415.

51. The 1000 Genomes Project Consortium. A global reference for human genetic variation. Nature. 2015;526 : 68–74. doi: 10.1038/nature15393 26432245

52. Danecek P, Auton A, Abecasis G, Albers CA, Banks E, DePristo MA, et al. The Variant Call Format and VCFtools. Bioinformatics. 2011;27 : 2156–2158. Version 0.1.13 [software]. Available from: https://vcftools.github.io/. doi: 10.1093/bioinformatics/btr330 21653522

53. Belsare S, Levy-Sakin M, Mostovoy Y, Durinck S, Chaudhuri S, Xiao M, et al. Evaluating the quality of the 1000 genomes project data. BMC Genomics. 2019;20 : 620. doi: 10.1186/s12864-019-5957-x 31416423

54. Excoffier L, Lischer HEL. Arlequin suite ver 3.5: A new series of programs to perform population genetics analyses under Linux and Windows. Mol Ecol Resour. 2010;10 : 564–567. Version 3.5.2.2 [software]. Available from: http://cmpg.unibe.ch/software/arlequin35/. doi: 10.1111/j.1755-0998.2010.02847.x 21565059

55. R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing. Vienna, Austria. Version 4.0.2 [software] 2014. Available from: https://www.R-project.org/.

56. Rousset F. Genepop’007: a complete reimplementation of the Genepop software for Windows and Linux. Mol Ecol Resour 2008;8 : 103–106. Version 4.7 [software]. Available from: https://genepop.curtin.edu.au/. doi: 10.1111/j.1471-8286.2007.01931.x 21585727

57. Abad-Grau M, Montes R, Sebastiani P. Building chromosome-wide LD maps. Bioinformatics. 2006;16 : 1933–1934. Version 3B [software]. Available from: http://bios.ugr.es/BMapBuilder. doi: 10.1093/bioinformatics/btl288 16782726

58. Garrison E. Vcflib, a simple C++ library for parsing and manipulating VCF files. Version 1.0.1–1 [software] 2016. Available from: https://github.com/vcflib/vcflib.

59. McVean GA, Myers SR, Hunt S, Deloukas P, Bentley DR, Donnelly P. The fine-scale structure of recombination rate variation in the human genome. Science. 2004;304 : 581–584. Version 2.2 [software]. Available from: http://ldhat.sourceforge.net/. doi: 10.1126/science.1092500 15105499

60. Fearnhead P, Donnelly PJ. Estimating recombination rates from population genetic data. Genetics. 2001;159 : 1299–1318. 11729171

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