Skip to main content

Advertisement

SpringerLink
Log in

Molecular characterisation of the pericentric inversion that distinguishes human chromosome 5 from the homologous chimpanzee chromosome

  • Original Investigation
  • Published:
Human Genetics Aims and scope Submit manuscript

Abstract

Human and chimpanzee karyotypes differ by virtue of nine pericentric inversions that serve to distinguish human chromosomes 1, 4, 5, 9, 12, 15, 16, 17, and 18 from their chimpanzee orthologues. In this study, we have analysed the breakpoints of the pericentric inversion characteristic of chimpanzee chromosome 4, the homologue of human chromosome 5. Breakpoint-spanning BAC clones were identified from both the human and chimpanzee genomes by fluorescence in situ hybridisation, and the precise locations of the breakpoints were determined by sequence comparisons. In stark contrast to some other characterised evolutionary rearrangements in primates, this chimpanzee-specific inversion appears not to have been mediated by either gross segmental duplications or low-copy repeats, although micro-duplications were found adjacent to the breakpoints. However, alternating purine–pyrimidine (RY) tracts were detected at the breakpoints, and such sequences are known to adopt non-B DNA conformations that are capable of triggering DNA breakage and genomic rearrangements. Comparison of the breakpoint region of human chromosome 5q15 with the orthologous regions of the chicken, mouse, and rat genomes, revealed similar but non-identical syntenic disruptions in all three species. The clustering of evolutionary breakpoints within this chromosomal region, together with the presence of multiple pathological breakpoints in the vicinity of both 5p15 and 5q15, is consistent with the non-random model of chromosomal evolution and suggests that these regions may well possess intrinsic features that have served to mediate a variety of genomic rearrangements, including the pericentric inversion in chimpanzee chromosome 4.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1a–d
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Abeysinghe SS, Chuzhanova N, Krawczak M, Ball EV, Cooper DN (2003) Translocation and gross deletion breakpoints in human inherited disease and cancer. I: Nucleotide composition and recombination-associated motifs. Hum Mutat 22:229–244

    CAS  PubMed  Google Scholar 

  • Anderson K, Arvidsson I, Jacobsson B, Hast R (2002) Fluorescence in situ hybridization for the study of cell lineage involvement in myelodysplastic syndromes with chromosome 5 anomalies. Cancer Genet Cytogenet 136:101–107

    CAS  PubMed  Google Scholar 

  • Bacolla A, Wells RD (2004) Non-B DNA conformations, genomic rearrangements, and human disease. J Biol Chem 279:47411–47414

    CAS  PubMed  Google Scholar 

  • Bacolla A, Jaworski A, Larson JE, Jakupciak JP, Chuzhanova N, Abeysinghe SS, O’Connell CD, Cooper DN, Wells RD (2004) Breakpoints of gross deletions coincide with non-B DNA conformations. Proc Natl Acad Sci USA 101:14162–14167

    CAS  PubMed  Google Scholar 

  • Bailey JA, Baertsch R, Kent WJ, Haussler D, Eichler EE (2004) Hotspots of mammalian chromosomal evolution. Genome Biol 5:R23

    PubMed  Google Scholar 

  • Caceres M, Lachuer J, Zapala MA, Redmond JC, Kudo L, Geschwind DH (2003) Elevated gene expression levels distinguish human from non-human primate brains. Proc Natl Acad Sci USA 100:13030–13035

    CAS  PubMed  Google Scholar 

  • Caligiuri MA, Strout MP, Schichman SA, Mrozek K, Arthur DC, Herzig GP, Baer MR, Schiffer CA, Heinonen K, Knuutila S, Nousiainen T, Ruutu T, Block AW, Schulman P, Pedersen-Bjergaard J, Croce CM, Bloomfield CD (1996) Partial tandem duplication of ALL1 as a recurrent molecular defect in acute myeloid leukemia with trisomy 11. Cancer Res 56:1418–1425

    CAS  PubMed  Google Scholar 

  • Casas S, Aventin A, Fuentes F, Vallespi T, Granada I, Carrio A, Angel Martinez-Climent J, Sole F, Teixido M, Bernues M, Duarte J, Maria Hernandez J, Brunet S, Dolors Coll M, Sierra J (2004) Genetic diagnosis by comparative genomic hybridization in adult de novo acute myelocytic leukemia. Cancer Genet Cytogenet 153:16–25

    CAS  PubMed  Google Scholar 

  • Courseaux A, Richard F, Grosgeorge J, Ortola C, Viale A, Turc-Carel C (2003) Segmental duplications in euchromatic regions of human chromosome 5: a source of evolutionary instability and transcriptional innovation. Genome Res 13:369–381

    CAS  PubMed  Google Scholar 

  • Dennehey BK, Gutches DG, McConkey EH, Krauter KS (2004) Inversion, duplication, and changes in gene context are associated with human chromosome 18 evolution. Genomics 83:493–501

    CAS  PubMed  Google Scholar 

  • Dutrillaux B (1979) Chromosomal evolution in primates: tentative phylogeny from Microcebus murinus (Prosimian) to man. Hum Genet 48:251–314

    CAS  PubMed  Google Scholar 

  • Dutrillaux B, Rethore MO, Lejeune J (1975) Comparison of the karyotype of the orangutan (Pongo pygmaeus) to those of man, chimpanzee, and gorilla. Ann Genet 18:153161

    Google Scholar 

  • Eder V, Ventura M, Ianigro M, Teti M, Rocchi M, Archidiacono N (2003). Chromosome 6 phylogeny in primates and centromere repositioning. Mol Biol Evol 20:1506–1512

    CAS  PubMed  Google Scholar 

  • Enard W, Khaitovich P, Klose J, Zollner S, Heissig F, Giavalisco P, Nieselt-Struwe K, Muchmore E, Varki A, Ravid R, Doxiadis GM, Bontrop RE, Paabo S(2002) Intra- and interspecific variation in primate gene expression patterns. Science 296:340–343

    CAS  PubMed  Google Scholar 

  • Fan Y, Linardopoulou E, Friedman C, Williams E, Trask BJ (2002) Genomic structure and evolution of the ancestral chromosome fusion site in 2q13–2q14.1 and paralogous regions on other human chromosomes. Genome Res 12:1651–1662

    CAS  PubMed  Google Scholar 

  • Frazer KA, Chen X, Hinds DA, Pant PV, Patil N, Cox DR (2003) Genomic DNA insertions and deletions occur frequently between humans and nonhuman primates. Genome Res 13:341–346

    CAS  PubMed  Google Scholar 

  • Goidts V, Szamalek JM, Hameister H, Kehrer-Sawatzki H (2004) Segmental duplication associated with the human specific inversion of chromosome 18: further example of the impact of segmental duplications on karyotype and genome evolution in primates. Hum Genet 115:116–122

    CAS  PubMed  Google Scholar 

  • Goidts V, Szamalek JM, de Jong PJ, Cooper DN, Chuzhanova N, Hameister H, Kehrer-Sawatzki H (2005) Independent intra-chromosomal recombination events underlie the pericentric inversions of chimpanzee and gorilla chromosomes homologous to human chromosome 16. Genome Res, in press.

  • Gusev VD, Nemytikova LA, Chuzhanova NA (1999) On the complexity measures of genetic sequences. Bioinformatics 15:994–999

    CAS  PubMed  Google Scholar 

  • Heller A, Loncarevic IF, Glaser M, Gebhart E, Trautmann U, Claussen U, Liehr T (2004) Breakpoint differentiation in chromosomal aberrations of hematological malignancies: identification of 33 previously unrecorded breakpoints. Int J Oncol 24:127–136

    CAS  PubMed  Google Scholar 

  • IJdo JW, Baldini A, Ward DC, Reeders ST, Wells RA (1991) Origin of human chromosome 2: an ancestral telomere-telomere fusion. Proc Natl Acad Sci USA 88:9051–9055

    CAS  PubMed  Google Scholar 

  • Karaman MW, Houck ML, Chemnick LG, Nagpal S, Chawannakul D, Sudano D, Pike BL, Ho VV, Ryder OA, Hacia JG (2003) Comparative analysis of gene-expression patterns in human and African great ape cultured fibroblasts. Genome Res 13:1619–1630

    CAS  PubMed  Google Scholar 

  • Kehrer-Sawatzki H, Schreiner B, Taenzer S, Platzer M, Müller S, Hameister H (2002) Molecular characterization of the pericentric inversion that causes differences between chimpanzee chromosome 19 and human chromosome 17. Am J Hum Genet 71:375–388

    CAS  PubMed  Google Scholar 

  • Kehrer-Sawatzki H, Sandig C, Chuzhanova N, Goidts V, Szamalek JM, Taenzer S, Müller S, Platzer M, Cooper DN, Hameister H (2005a) Breakpoint analysis of the pericentric inversion distinguishing human chromosome 4 from the homologous chromosome in the chimpanzee (Pan troglodytes). Hum Mutat 25:45–55

    CAS  Google Scholar 

  • Kehrer-Sawatzki H, Sandig CA, Goidts V, Hameister H (2005b) Breakpoint analysis of the pericentric inversion between chimpanzee chromosome 10 and the homologous chromosome 12 in humans. Cytogenet Genome Res 108:91–97

    CAS  Google Scholar 

  • Kehrer-Sawatzki H, Szamalek JM, Taenzer S, Platzer M, Hameister H (2005c) Molecular characterization of the pericentric inversion of chimpanzee chromosome 11 homologous to human chromosome 9. Genomics 85: 542–550

    Google Scholar 

  • Khaitovich P, Muetzel B, She X, Lachmann M, Hellmann I, Dietzsch J, Steigele S, Do HH, Weiss G, Enard W, Heissig F, Arendt T, Nieselt-Struwe K, Eichler EE, Pääbo S (2004) Regional patterns of gene expression in human and chimpanzee brains. Genome Res 14:1462–1473

    CAS  PubMed  Google Scholar 

  • Locke DP, Archidiacono N, Misceo D, Cardone MF, Deschamps S, Roe B, Rocchi M, Eichler EE (2003) Refinement of a chimpanzee pericentric inversion breakpoint to a segmental duplication cluster. Genome Biol 4:R50

    PubMed  Google Scholar 

  • Mainardi PC, Perfumo C, Cali A, Coucourde G, Pastore G, Cavani S, Zara F, Overhauser J, Pierluigi M, Bricarelli FD (2001) Clinical and molecular characterisation of 80 patients with 5p deletion: genotype-phenotype correlation. J Med Genet 38:151–158

    CAS  PubMed  Google Scholar 

  • Marzella R, Viggiano L, Miolla V, Storlazzi CT, Ricco A, Gentile E, Roberto R, Surace C, Fratello A, Mancini M, Archidiacono N, Rocchi M (2000) Molecular cytogenetic resources for chromosome 4 and comparative analysis of phylogenetic chromosome IV in great apes. Genomics 63:307–313

    CAS  PubMed  Google Scholar 

  • McConkey EH (1997) The origin of human chromosome 18 from a human/ape ancestor. Cytogenet Cell Genet 76:189–191

    CAS  PubMed  Google Scholar 

  • Mendes-da-Silva P, Moreira A, Duro-da-Costa J, Matias D, Monteiro C (2000) Frequent loss of heterozygosity on chromosome 5 in non-small cell lung carcinoma. Mol Pathol 53:184–187

    CAS  PubMed  Google Scholar 

  • Montefalcone G, Tempesta S, Rocchi M, Archidiacono N (1999) Centromere repositioning. Genome Res 9:1184–1188

    CAS  PubMed  Google Scholar 

  • Müller S, Wienberg J (2001) “Bar-coding” primate chromosomes: molecular cytogenetic screening for the ancestral hominoid karyotype. Hum Genet 109:85–94

    PubMed  Google Scholar 

  • Müller S, Finelli P, Neusser M, Wienberg J (2004) The evolutionary history of human chromosome 7. Genomics 84:458–467

    PubMed  Google Scholar 

  • Nickerson E, Nelson DL (1998) Molecular definition of pericentric inversion breakpoints occurring during the evolution of humans and chimpanzees. Genomics 50:368–372

    CAS  PubMed  Google Scholar 

  • de Pontbriand A, Wang XP, Cavaloc Y, Mattei MG, Galibert F (2002) Synteny comparison between apes and human using fine-mapping of the genome. Genomics 80:395–401

    PubMed  Google Scholar 

  • Ruiz-Herrera A, Garcia F, Mora L, Egozcue J, Ponsa M, Garcia M (2005) Evolutionary conserved chromosomal segments in the human karyotype are bounded by unstable chromosome bands. Cytogenet Genome Res 108:161–174

    CAS  PubMed  Google Scholar 

  • Schmutz J, Martin J, Terry A et al (2004) The DNA sequence and comparative analysis of human chromosome 5. Nature 431:268–274

    CAS  PubMed  Google Scholar 

  • Shimada MK, Kim CG, Kitano T, Ferrell RE, Kohara Y, Saitou N (2005) Nucleotide sequence comparison of a chromosome rearrangement on human chromosome 12 and the corresponding ape chromosomes. Cytogenet Genome Res 108:83–90

    CAS  PubMed  Google Scholar 

  • Spitzner JR, Chung IK, Muller MT (1990) Eukaryotic topoisomerase II preferentially cleaves purine–pyrimidine repeats. Nucleic Acids Res 18:1–11

    CAS  PubMed  Google Scholar 

  • Stankiewicz P, Park SS, Inoue K, Lupski JR (2001) The evolutionary chromosome translocation 4;19 in Gorilla gorilla is associated with microduplication of the chromosome fragment syntenic to sequences surrounding the human proximal CMT1A-REP. Genome Res 11:1205–1210

    CAS  PubMed  Google Scholar 

  • Stankiewicz P, Shaw CJ, Withers M, Inoue K, Lupski JR (2004) Serial segmental duplications during primate evolution result in complex human genome architecture. Genome Res 14:2209–2220

    CAS  PubMed  Google Scholar 

  • Tsend-Ayush E, Grützner F, Yue Y, Grossmann B, Hansel U, Sudbrak R, Haaf T (2004) Plasticity of human chromosome 3 during primate evolution. Genomics 83:193–202

    CAS  PubMed  Google Scholar 

  • Uddin M, Wildman DE, Liu G, Xu W, Johnson RM, Hof PR, Kapatos G, Grossman LI, Goodman M (2004) Sister grouping of chimpanzees and humans as revealed by genome-wide phylogenetic analysis of brain gene expression profiles. Proc Natl Acad Sci USA 101:2957–2962

    CAS  PubMed  Google Scholar 

  • van Geel M, Eichler EE, Beck AF, Shan Z, Haaf T, van der Maarel SM, Frants RR, de Jong PJ (2002) A cascade of complex subtelomeric duplications during the evolution of the hominoid and Old World monkey genomes. Am J Hum Genet 70:269–278

    PubMed  Google Scholar 

  • Weise A, Starke H, Mrasek K, Claussen U, Liehr T (2005) New insights into the evolution of chromosome 1. Cytogenet Genome Res 108:217–222

    CAS  PubMed  Google Scholar 

  • Wienberg J, Jauch A, Stanyon R, Cremer T (1990) Molecular cytotaxonomy of primates by chromosomal in situ suppression hybridization. Genomics 8:347–350

    CAS  PubMed  Google Scholar 

  • Yunis JJ, Prakash O (1982) The origin of man: a chromosomal pictorial legacy. Science 215:1525–1530

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This research was funded by the Deutsche Forschungsgemeinschaft (DFG KE 724/2-1).

Author information

Authors and Affiliations

  1. Department of Human Genetics, University of Ulm, Albert-Einstein-Allee 11, 89081, Ulm, Germany

    Justyna M. Szamalek, Violaine Goidts, Horst Hameister & Hildegard Kehrer-Sawatzki

  2. Institute of Medical Genetics, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK

    Nadia Chuzhanova & David N. Cooper

  3. Biostatistics and Bioinformatics Unit, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK

    Nadia Chuzhanova

Authors
  1. Justyna M. Szamalek
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Violaine Goidts
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nadia Chuzhanova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Horst Hameister
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David N. Cooper
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hildegard Kehrer-Sawatzki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hildegard Kehrer-Sawatzki.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Szamalek, J.M., Goidts, V., Chuzhanova, N. et al. Molecular characterisation of the pericentric inversion that distinguishes human chromosome 5 from the homologous chimpanzee chromosome. Hum Genet 117, 168–176 (2005). https://doi.org/10.1007/s00439-005-1287-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00439-005-1287-y

Keywords

Search

Navigation