, Volume 128, Issue 1, pp 1–6 | Cite as

Chromothripsis, a credible chromosomal mechanism in evolutionary process

  • Franck PellestorEmail author
  • Vincent Gatinois


The recent discovery of a new class of massive chromosomal rearrangements, occurring during one unique cellular event and baptized “chromothripsis,” deeply modifies our perception on the genesis of complex genomic rearrangements, but also, it raises the question of the potential driving role of chromothripsis in species evolution. Analyses of the etiology of chromothripsis have led to the identification of various cellular processes capable of generating chromothripsis, such as premature chromosome condensation, telomere dysfunction, abortive apoptosis, and micronucleus formation. All these causative mechanisms may occur in germlines or during early embryonic development, suggesting that chromothripsis could be an unexpected mechanism for profound genome modification. The occurrence of chromothripsis appears to be in good agreement with macroevolution models proposed as a complement to phyletic gradualism. Various cases of chromosomal speciation and short-term adaptation could be correlated to chromothripsis-mediated mechanism. The emergency of this unanticipated chaotic phenomenon may contribute to demonstrate the contribution of chromosome rearrangements to speciation process. New sequencing and bioinformatics methods can be expected to shed new light on the role of chromothripsis in evolutionary process.


Chromothripsis Chromosomal rearrangements Macroevolution Speciation Adaptation 



Work in the unit of Chromosomal Genetics is supported by the CHU research platform CHROMOSTEM (


  1. Beck CR, Garcia-Perez JL, Badge RM, Moran JV (2011) LINE-I elements in structural variation and disease. Annu Rev Genom Hum Genet 12:187–215Google Scholar
  2. Becker SE, Thomas R, Trifonov VA et al (2011) Anchoring the dog to its relatives reveals new evolutionary breakpoints across 11 species of the Canidae and provides new clues for the role of B chromosomes. Chromosom Res 19:685–708Google Scholar
  3. Bertelsen B, Nazaryan-Petersen L, Sun W, Mehrjouy MM, Xie G, Chen W, Hjermind LE, Taschner PEM, Tümer Z (2016) A germline chromothripsis event stably segregating in 11 individuals through three generations. Genet Med 18(5):494–500. Google Scholar
  4. Britton-Davidian J, Catalan J, Ramalhinho M et al (2000) Rapid chromosomal evolution in island mice. Nature 403:158Google Scholar
  5. Burns KH (2017) Transposable elements in cancer. Nat Rev Cancer 17:415–424Google Scholar
  6. Carbone L, Harris RA, Gnerre S et al (2014) Gibbon genome and the fast karyotype evolution of small apes. Nature 513:195–201Google Scholar
  7. Chan C, Jayasekera S, Kao B et al (2015) Remodelling of a homeobox gene cluster by multiple independent gene reunions in Drosophila. Nat Commun 6:6509. Google Scholar
  8. Chouard T (2010) Revenge of the hopeful monster. Nature 463:864–867Google Scholar
  9. Collins RL, Brand H, Redin CE, Hanscom C, Antolik C, Stone MR, Glessner JT, Mason T, Pregno G, Dorrani N, Mandrile G, Giachino D, Perrin D, Walsh C, Cipicchio M, Costello M, Stortchevoi A, An JY, Currall BB, Seabra CM, Ragavendran A, Margolin L, Martinez-Agosto JA, Lucente D, Levy B, Sanders SJ, Wapner RJ, Quintero-Rivera F, Kloosterman W, Talkowski ME (2017) Defining the diverse spectrum of inversions, complex structural variation, and chromothripsis in the morbid human genome. Genome Biol 18(1):36. Google Scholar
  10. Coyne JAZ (1989) A test of the role of meiotic drive in chromosome evolution. Genetics 123:241–243Google Scholar
  11. Crasta K, Ganem NJ, Dagher R, Lantermann AB, Ivanova EV, Pan Y, Nezi L, Protopopov A, Chowdhury D, Pellman D (2012) DNA breaks and chromosome pulverization from errors in mitosis. Nature 482:53–58Google Scholar
  12. Crombach A, Hogeweg P (2007) Chromosome rearrangements and the evolution of genome structuring and adaptability. Mol Biol Evol 24(5):1130–1139Google Scholar
  13. de Pagter MS, van Roosmalen MJ, Baas AF, Renkens I, Duran KJ, van Binsbergen E, Tavakoli-Yaraki M, Hochstenbach R, van der Veken L, Cuppen E, Kloosterman WP (2015) Chromothripsis in healthy individuals affects multiple protein-coding genes and can result in severe congenital abnormalities in offspring. Am J Hum Genet 96(4):651–656Google Scholar
  14. Deakin JE (2018) Chromosome evolution in marsupials. Genes 9(2):72. Google Scholar
  15. Dennis MY, Harshman L, Nelson BJ et al (2017) The evolution and population diversity of human-specific segmental duplications. Nat Ecol Evol.
  16. Dittrich-Reed DR, Fitzpatrick B (2013) Transgressive hybrids as hopeful monsters. Evol Biol 40:310–315Google Scholar
  17. Dutrillaux B (1979) Chromosomal evolution in primates: tentative phylogeny from Microcebus murinus (prosimian) to man. Hum Genet 48:251–314Google Scholar
  18. Dyer KA, Charlesworth B, Jaenike J (2007) Chromosome-wide linkage disequilibrium as a consequence of meiotic drive. Proc Natl Acad Sci U S A 104:1587–1592Google Scholar
  19. Eldredge N, Gould SJ (1972) Punctuated equilibria: an alternative to phyletic gradualism. In: Schopf TJM (ed) Models in paleobiology. Freeman Cooper, San Francisco, pp 82–115Google Scholar
  20. Faria R, Navarro A (2010) Chromosomal speciation revisited: rearranging theory with pieces of evidence. Trends Ecol Evol 25(11):660–669Google Scholar
  21. Froment JV, Kaidi A, Jackson SP (2012) Chromothripsis and cancer: causes and consequences of chromosome shattering. Nat Rev Cancer 12(10):663–670Google Scholar
  22. Fukami M, Shima H, Suzuki E, Ogata T, Matsubara K, Kamimaki T (2017) Catastrophic cellular events leading to complex chromosomal rearrangements in the germline. Clin Genet 91:653–660Google Scholar
  23. Goldschmidt R (1940) The material basis of evolution. Yale University Press, New HavenGoogle Scholar
  24. Gompert Z, Fordyce JA, Forister ML et al (2006) Homoploid hybrid speciation in an extreme habitat. Science 314:1923–1925Google Scholar
  25. Gould SJ, Eldredge N (1993) Punctuated equilibrium comes of age. Nature 366:223–227Google Scholar
  26. Govind SK, Zia A, Hennings-Yeomans PH, Watson JD, Fraser M, Anghel C, Wyatt AW, van der Kwast T, Collins CC, McPherson JD, Bristow RG, Boutros PC (2014) ShatterProof: operational detection and quantification of chromothripsis. BMC Bioinformatics 15:78. Google Scholar
  27. Gu S, Szafranski P, Akdemir ZC (2016) Mechanisms for complex chromosomal insertions. PLoS Genet 12(11):e1006446. Google Scholar
  28. Hancks D (2018) A role for retrotransposons in chromothripsis. In: Pellestor F (ed) Chromothripsis. Methods and protocols. Humana Press, New York, pp 169–182Google Scholar
  29. Herrel A, Huyghe K, Vanhooydonck B, Backeljau T, Breugelmans K, Grbac I, van Damme R, Irschick DJ (2008) Rapid large-scale evolutionary divergence in morphology and performance associated with exploitation of a different dietary resource. Proc Natl Acad Sci U S A 105(12):4792–4795Google Scholar
  30. Hufton AL, Grothe D, Vingron M et al (2008) Early vertebrate whole genome duplication were predated by a period of intense genome rearrangement. Genome Res 18:1582–1591Google Scholar
  31. Ivkov R, Bunz F (2015) Pathways to chromothripsis. Cell Cycle 14(18):2886–2890Google Scholar
  32. Klein SJ, O’Neill RJ (2018) Transposable elements: genome innovation, chromosome diversity, and centromere conflict. Chromosom Res 26:5–23Google Scholar
  33. Kloosterman WP, Gurvey V, van Roosmalen M et al (2011) Chromothripsis as a mechanism driving complex de novo structural rearrangements in the germline. Hum Mol Genet 20:1916–1924Google Scholar
  34. Korbel JO, Campbell PJ (2013) Criteria for inference of chromothripsis in cancer genomes. Cell 152:1226–1236Google Scholar
  35. Larhammar D, Lundin LG, Hallbook F (2002) The human Hox-bearing chromosome regions did arise by block or chromosome (or even genome) duplications. Genome Res 12:1910–1920Google Scholar
  36. Lässig M, Mustonen V, Walczak AM (2017) Predicting evolution. Nat Ecol Evol 1:0077. Google Scholar
  37. Li W, Challa GS, Zhu H, Wei W (2016) Recurrence of chromosome rearrangements and reuse of DNA breakpoints in the evolution of the Triticeae genomes. G3 6(12):3837–3847. Google Scholar
  38. Lupianez DG, Spielmann M, Mundlos S (2016) Breaking TADs: how alterations of chromatin domains result in disease. Trends Genet 33(4):225–237Google Scholar
  39. Lynch VJ, Wagner GP (2009) Multiple chromosomal rearrangements structured the ancestral vertebrate Hox-bearing protochromosomes. PLoS Genet 5(1):e1000349. Google Scholar
  40. Macera MJ, Sobrino A, Levy B, Jobanputra V, Aggarwal V, Mills A, Esteves C, Hanscom C, Pereira S, Pillalamarri V, Ordulu Z, Morton CC, Talkowski M, Warburton D (2015) Prenatal diagnosis of chromothripsis, with nine breaks characterized by karyotyping, FISH, microarray and whole-genome sequencing. Prenat Diagn 35:299–301Google Scholar
  41. Mallet J (2007) Hybrid speciation. Nature 446:279–283Google Scholar
  42. McDermott DH, Gao JL, Liu Q et al (2015) Chromothriptic cure of WHIM syndrome. Cell 160:686–699Google Scholar
  43. Meyer TJ, Held U, Nevonen KA, Klawitter S, Pirzer T, Carbone L, Schumann GG (2016) The flow of the gibbon LAVA element s facilitated by the LINE-1 retrotransposition machinery. Genome Biol Evol 8:3209–3225Google Scholar
  44. Molenaar JJ, Koster J, Zwijnenburg DA, van Sluis P, Valentijn LJ, van der Ploeg I, Hamdi M, van Nes J, Westerman BA, van Arkel J, Ebus ME, Haneveld F, Lakeman A, Schild L, Molenaar P, Stroeken P, van Noesel MM, Øra I, Santo EE, Caron HN, Westerhout EM, Versteeg R (2012) Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes. Nature 483:589–593Google Scholar
  45. Nazaryan-Petersen L, Bertelsen B, Bak M, Jønson L, Tommerup N, Hancks DC, Tümer Z (2016) Germline chromothripsis driven by L1-mediated retrotransposition and Alu/Alu homologous recombination. Hum Mutat 37(4):385–395Google Scholar
  46. Neme R, Amador C, Yildirim B, McConnell E, Tautz D (2017) Random sequences are an abundant source of bioactive RNAs or peptides. Nat Ecol Evol 1(6):0217. Google Scholar
  47. Newman TL, Tuzun E, Morrison VA, Hayden KE, Ventura M, McGrath S, Rocchi M, Eichler EE (2005) A genome-wide survey of structural variation between human and chimpanzee. Genome Res 15:1344–1356Google Scholar
  48. Noor MAF, Grams KL, Bertucci LA, Reiland J (2001) Chromosomal inversions and the reproductive isolation of species. Proc Natl Acad Sci U S A 98:12084–12088Google Scholar
  49. Notta F, Chang-Seng-Yue M, Lemire M et al (2016) A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns. Nature 538(7625):378–382Google Scholar
  50. Pellestor F, Gatinois V, Puechberty J, Geneviève D, Lefort G (2014) Chromothripsis: potential origin in gametogenesis and preimplantation cell divisions. A review. Fertil Steril 102:1785–1796Google Scholar
  51. Pevzner P, Tesler G (2003) Genome rearrangements in mammalian evolution: lessons from human and mouse genomes. Genome Res 13:37–45Google Scholar
  52. Platt RN II, Vandewege MW, Ray DA (2018) Mammalian transposable elements and their impacts on genome evolution. Chromosom Res 26:25–43Google Scholar
  53. Rausch T, Jones DTW, Zapatka M, Stütz AM, Zichner T, Weischenfeldt J, Jäger N, Remke M, Shih D, Northcott PA, Pfaff E, Tica J, Wang Q, Massimi L, Witt H, Bender S, Pleier S, Cin H, Hawkins C, Beck C, von Deimling A, Hans V, Brors B, Eils R, Scheurlen W, Blake J, Benes V, Kulozik AE, Witt O, Martin D, Zhang C, Porat R, Merino DM, Wasserman J, Jabado N, Fontebasso A, Bullinger L, Rücker FG, Döhner K, Döhner H, Koster J, Molenaar JJ, Versteeg R, Kool M, Tabori U, Malkin D, Korshunov A, Taylor MD, Lichter P, Pfister SM, Korbel JO (2012) Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations. Cell 148:59–71Google Scholar
  54. Razin SV, Vassetzky YS (2017) 3D genomics imposes evolution of the domain model of eukaryotic genome organization. Chromosoma 126:59–69Google Scholar
  55. Reiseberg LH (2001) Chromosomal rearrangements and speciation. Trends Ecol Evol 16(7):351–358Google Scholar
  56. Reiseberg LH, Archer MA, Wayne RK (1999) Transgressive segregation, adaptation and speciation. Heredity 83:363–372Google Scholar
  57. Rode A, Maass KK, Willmund KV et al (2016) Chromothripsis in cancer cells: an update. Int J Cancer 138:2322–2333Google Scholar
  58. Romanenko SA, Serdyukova NA, Perelman PL et al (2017) Intrachromosomal rearrangements in rodents from the perspective of comparative region-specific painting. Genes 8(9). doi:
  59. Ruban A, Schmutzer T, Scholz U et al. (2017) How next-generation sequencing has aided our understanding of the sequence composition and origin of B chromosomes. Genes 8(11). doi:
  60. Sheldon PR (1990) Shaking up evolutionary patterns. Nature 345:772Google Scholar
  61. Shubert I, Lysak MA (2011) Interpretation of karyotype evolution should consider chromosome structural constraints. Trends Genet 27:207–215Google Scholar
  62. Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR, Mudie LJ, Pleasance ED, Lau KW, Beare D, Stebbings LA, McLaren S, Lin ML, McBride DJ, Varela I, Nik-Zainal S, Leroy C, Jia M, Menzies A, Butler AP, Teague JW, Quail MA, Burton J, Swerdlow H, Carter NP, Morsberger LA, Iacobuzio-Donahue C, Follows GA, Green AR, Flanagan AM, Stratton MR, Futreal PA, Campbell PJ (2011) Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell 144:27–40Google Scholar
  63. Symer DE, Connelly C, Szak ST, Caputo EM, Cost GJ, Parmigiani G, Boeke JD (2002) Human L1 retrotransposition is associated with genetic instability in vivo. Cell 110:327–328Google Scholar
  64. Tan EH, Henry IM, Ravi M et al (2015) Catastrophic chromosomal restructuring during genome elimination in plants. Elife 15:4. Google Scholar
  65. Touati SA, Wassmann K (2016) How oocytes try to get it right: spindle checkpoint control in meiosis. Chromosoma 125:321–335Google Scholar
  66. Tubio JMC, Estivill X (2011) When catastrophe strikes a cell. Nature 470:476–477Google Scholar
  67. Wang L, Rishishwar L, Marino-Ramirez L et al (2017) Human population-specific gene expression and transcriptional network modification with polymorphic transposable elements. Nucleic Acids Res 45:2318–2328Google Scholar
  68. Way GP, Younstrom DW, Hankenson KD et al (2017) Implicating candidate genes at GWAS signals by leveraging topologically associating domains. Eur J Hum Genet 25:1286–1289Google Scholar
  69. Weckselblatt B, Hermetz KE, Rudd MK (2015) Unbalanced translocations arise from diverse mutational mechanisms including chromothripsis. Genome Res 25:937–947Google Scholar
  70. Wilson BA, Foy SG, Neme R, Masel J (2017) Young genes are highly disordered as predicted by the preadaptation hypothesis of de novo gene birth. Nat Ecol Evol 1(6):0146–0146. Google Scholar
  71. Yang J, Liu J, Ouyang et al (2016) CTLPScanner: a web server for chromothripsis-like pattern detection. Nucleic Acids Res 44(W1):W252–W258. Google Scholar
  72. Yunis JJ, Sawyer JR, Dunham K (1980) The striking resemblance of high-resolution g-banded chromosomes of man and chimpanzee. Science 208:145–1148Google Scholar
  73. Zhang CZ, Spektor A, Cornils H, Francis JM, Jackson EK, Liu S, Meyerson M, Pellman D (2015) Chromothripsis from DNA damage in micronuclei. Nature 522:179–184Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Unit of Chromosomal Genetics, Department of Medical GeneticsArnaud de Villeneuve Hospital, Montpellier CHRUMontpellier CEDEX 5France
  2. 2.INSERM 1183 “Genome and Stem Cell Plasticity in Development and Aging,” St Eloi HospitalInstitute of Regenerative Medicine and BiotherapiesMontpellierFrance

Personalised recommendations