Recombination Dynamics of a Human Y-Chromosomal Palindrome: Rapid GC-Biased Gene Conversion, Multi-kilobase Conversion Tracts, and Rare Inversions

English version České info

The male-specific region of the human Y chromosome (MSY) includes eight large inverted repeats (palindromes) in which arm-to-arm similarity exceeds 99.9%, due to gene conversion activity. Here, we studied one of these palindromes, P6, in order to illuminate the dynamics of the gene conversion process. We genotyped ten paralogous sequence variants (PSVs) within the arms of P6 in 378 Y chromosomes whose evolutionary relationships within the SNP-defined Y phylogeny are known. This allowed the identification of 146 historical gene conversion events involving individual PSVs, occurring at a rate of 2.9–8.4×10⁻⁴ events per generation. A consideration of the nature of nucleotide change and the ancestral state of each PSV showed that the conversion process was significantly biased towards the fixation of G or C nucleotides (GC-biased), and also towards the ancestral state. Determination of haplotypes by long-PCR allowed likely co-conversion of PSVs to be identified, and suggested that conversion tract lengths are large, with a mean of 2068 bp, and a maximum in excess of 9 kb. Despite the frequent formation of recombination intermediates implied by the rapid observed gene conversion activity, resolution via crossover is rare: only three inversions within P6 were detected in the sample. An analysis of chimpanzee and gorilla P6 orthologs showed that the ancestral state bias has existed in all three species, and comparison of human and chimpanzee sequences with the gorilla outgroup confirmed that GC bias of the conversion process has apparently been active in both the human and chimpanzee lineages.

Vyšlo v časopise: Recombination Dynamics of a Human Y-Chromosomal Palindrome: Rapid GC-Biased Gene Conversion, Multi-kilobase Conversion Tracts, and Rare Inversions. PLoS Genet 9(7): e32767. doi:10.1371/journal.pgen.1003666
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003666

Souhrn

Zdroje

1. SkaletskyH, Kuroda-KawaguchiT, MinxPJ, CordumHS, HillierL, et al. (2003) The male-specific region of the human Y chromosome: a mosaic of discrete sequence classes. Nature 423 : 825–837.

2. RozenS, SkaletskyH, MarszalekJD, MinxPJ, CordumHS, et al. (2003) Abundant gene conversion between arms of massive palindromes in human and ape Y chromosomes. Nature 423 : 873–876.

3. 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.

4. Alföldi JE (2008) Sequence of the mouse Y chromosome. Cambridge, Massachusetts: Massachusetts Institute of Technology.

5. GeraldesA, RamboT, WingRA, FerrandN, NachmanMW (2010) Extensive gene conversion drives the concerted evolution of paralogous copies of the SRY gene in European rabbits. Mol Biol Evol 27 : 2437–2440.

6. BackströmN, CeplitisH, BerlinS, EllegrenH (2005) Gene conversion drives the evolution of HINTW, an ampliconic gene on the female-specific avian W chromosome. Mol Biol Evol 22 : 1992–1999.

7. DavisJK, ThomasPJ, ThomasJW (2010) A W-linked palindrome and gene conversion in New World sparrows and blackbirds. Chromosome Res 18 : 543–553.

8. Mendez-LagoM, BergmanCM, de PablosB, TraceyA, WhiteheadSL, et al. (2011) A large palindrome with interchromosomal gene duplications in the pericentromeric region of the D. melanogaster Y chromosome. Mol Biol Evol 28 : 1967–1971.

9. WarburtonPE, GiordanoJ, CheungF, GelfandY, BensonG (2004) Inverted repeat structure of the human genome: the X-chromosome contains a preponderance of large, highly homologous inverted repeats that contain testes genes. Genome Res 14 : 1861–1869.

10. BagnallRD, AyresKL, GreenPM, GiannelliF (2005) Gene conversion and evolution of Xq28 duplicons involved in recurring inversions causing severe hemophilia A. Genome Res 15 : 214–223.

11. ConnallonT, ClarkAG (2010) Gene duplication, gene conversion and the evolution of the Y chromosome. Genetics 186 : 277–286.

12. MaraisGA, CamposPR, GordoI (2010) Can intra-Y gene conversion oppose the degeneration of the human Y chromosome? A simulation study. Genome Biol Evol 2 : 347–357.

13. KarafetTM, MendezFL, MeilermanM, UnderhillPA, ZeguraSL, et al. (2008) New binary polymorphisms reshape and increase resolution of the human Y-chromosomal haplogroup tree. Genome Res 18 : 830–838.

14. XueY, WangQ, LongQ, NgBL, SwerdlowH, et al. (2009) Human Y chromosome base-substitution mutation rate measured by direct sequencing in a deep-rooting pedigree. Curr Biol 19 : 1453–1457.

15. CannHM, de TomaC, CazesL, LegrandMF, MorelV, et al. (2002) A human genome diversity cell line panel. Science 296 : 261–262.

16. ShiW, AyubQ, VermeulenM, ShaoRG, ZunigaS, et al. (2010) A worldwide survey of human male demographic history based on Y-SNP and Y-STR data from the HGDP-CEPH populations. Mol Biol Evol 27 : 385–393.

17. SenguptaS, ZhivotovskyLA, KingR, MehdiSQ, EdmondsCA, et al. (2006) Polarity and temporality of high-resolution Y-chromosome distributions in India identify both indigenous and exogenous expansions and reveal minor genetic influence of Central Asian pastoralists. Am J Hum Genet 78 : 202–221.

18. LiJZ, AbsherDM, TangH, SouthwickAM, CastoAM, et al. (2008) Worldwide human relationships inferred from genome-wide patterns of variation. Science 319 : 1100–1104.

19. 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.

20. ScallyA, DutheilJY, HillierLW, JordanGE, GoodheadI, et al. (2012) Insights into hominid evolution from the gorilla genome sequence. Nature 483 : 169–175.

21. MaraisG (2003) Biased gene conversion: implications for genome and sex evolution. Trends Genet 19 : 330–338.

22. ChenJM, CooperDN, ChuzhanovaN, FerecC, PatrinosGP (2007) Gene conversion: mechanisms, evolution and human disease. Nat Rev Genet 8 : 762–775.

23. AssisR, KondrashovAS (2012) Nonallelic gene conversion is not GC-biased in Drosophila or primates. Mol Biol Evol 29 : 1291–1295.

24. AdamsSM, KingTE, BoschE, JoblingMA (2006) The case of the unreliable SNP: recurrent back-mutation of Y-chromosomal marker P25 through gene conversion. Forensic Sci Int 159 : 14–20.

25. BoschE, HurlesME, NavarroA, JoblingMA (2004) Dynamics of a human interparalog gene conversion hotspot. Genome Res 14 : 835–844.

26. BouzekriN, TaylorPG, HammerMF, JoblingMA (1998) Novel mutation processes in the evolution of a haploid minisatellite, MSY1: array homogenization without homogenization. Hum Mol Genet 7 : 655–659.

27. TrombettaB, CrucianiF, UnderhillPA, SellittoD, ScozzariR (2010) Footprints of X-to-Y gene conversion in recent human evolution. Mol Biol Evol 27 : 714–725.

28. RosserZH, BalaresqueP, JoblingMA (2009) Gene conversion between the X chromosome and the male-specific region of the Y chromosome at a translocation hotspot. Am J Hum Genet 85 : 130–134.

29. IwaseM, SattaY, HiraiH, HiraiY, TakahataN (2010) Frequent gene conversion events between the X and Y homologous chromosomal regions in primates. BMC Evol Biol 10 : 225.

30. IwaseM, SattaY, HiraiY, HiraiH, ImaiH, et al. (2003) The amelogenin loci span an ancient pseudoautosomal boundary in diverse mammalian species. Proc Natl Acad Sci U S A 100 : 5258–5263.

31. MaraisG, GaltierN (2003) Sex chromosomes: how X-Y recombination stops. Curr Biol 13: R641–643.

32. Pecon SlatteryJ, Sanner-WachterL, O'BrienSJ (2000) Novel gene conversion between X-Y homologues located in the nonrecombining region of the Y chromosome in Felidae (Mammalia). Proc Natl Acad Sci USA 97 : 5307–5312.

33. ManceraE, BourgonR, BrozziA, HuberW, SteinmetzLM (2008) High-resolution mapping of meiotic crossovers and non-crossovers in yeast. Nature 454 : 479–485.

34. JeffreysAJ, MayCA (2004) Intense and highly localized gene conversion activity in human meiotic crossover hot spots. Nature Genet 36 : 152–156.

35. LangeJ, SkaletskyH, van DaalenSK, EmbrySL, KorverCM, et al. (2009) Isodicentric Y chromosomes and sex disorders as byproducts of homologous recombination that maintains palindromes. Cell 138 : 855–869.

36. ReppingS, van DaalenSK, BrownLG, KorverCM, LangeJ, et al. (2006) High mutation rates have driven extensive structural polymorphism among human Y chromosomes. Nat Genet 38 : 463–467.

37. GuillonH, BaudatF, GreyC, LiskayRM, de MassyB (2005) Crossover and noncrossover pathways in mouse meiosis. Mol Cell 20 : 563–573.

38. JeffreysAJ, HollowayJK, KauppiL, MayCA, NeumannR, et al. (2004) Meiotic recombination hot spots and human DNA diversity. Philos Trans R Soc Lond B Biol Sci 359 : 141–152.

39. HollowayK, LawsonVE, JeffreysAJ (2006) Allelic recombination and de novo deletions in sperm in the human beta-globin gene region. Hum Mol Genet 15 : 1099–1111.

40. BergIL, NeumannR, SarbajnaS, Odenthal-HesseL, ButlerNJ, et al. (2011) Variants of the protein PRDM9 differentially regulate a set of human meiotic recombination hotspots highly active in African populations. Proc Natl Acad Sci U S A 108 : 12378–12383.

41. SarbajnaS, DenniffM, JeffreysAJ, NeumannR, Soler ArtigasM, et al. (2012) A major recombination hotspot in the XqYq pseudoautosomal region gives new insight into processing of human gene conversion events. Hum Mol Genet 21 : 2029–2038.

42. DuretL, GaltierN (2009) Biased gene conversion and the evolution of mammalian genomic landscapes. Annu Rev Genomics Hum Genet 10 : 285–311.

43. ENCODE Project Consortium (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489 : 57–74.

44. LoschFO, BredenbeckA, HollsteinVM, WaldenP, WredeP (2007) Evidence for a large double-cruciform DNA structure on the X chromosome of human and chimpanzee. Hum Genet 122 : 337–343.

45. WangJ, FanHC, BehrB, QuakeSR (2012) Genome-wide single-cell analysis of recombination activity and de novo mutation rates in human sperm. Cell 150 : 402–412.

46. BatiniC, FerriG, Destro-BisolG, BrisighelliF, LuiselliD, et al. (2011) Signatures of the pre-agricultural peopling processes in sub-Saharan Africa as revealed by the phylogeography of early Y chromosome lineages. Mol Biol Evol 28 : 2603–2613.

47. ArmourJA, PallaR, ZeeuwenPL, den HeijerM, SchalkwijkJ, et al. (2007) Accurate, high-throughput typing of copy number variation using paralogue ratios from dispersed repeats. Nucleic Acids Res 35: e19.

48. SullivanKM, MannucciA, KimptonCP, GillP (1993) A rapid and quantitative DNA sex test -⁠ fluorescence-based PCR analysis of X-Y homologous gene amelogenin. Biotechniques 15 : 636.

49. WeiW, AyubQ, ChenY, McCarthyS, HouY, et al. (2013) A calibrated human Y-chromosomal phylogeny based on resequencing. Genome Res 23 : 388–395.