Home LiteratureArticle Details
PMID: 15173109 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The small chromosomes of Trypanosoma brucei involved in antigenic variation are constructed around repetitive palindromes.

Genome research ·Vol. 14 ·No. 6 ·2004-06-00 ·Pages 1014-24

Wickstead B, Ersfeld K, Gull K

Abstract

Most eukaryotic genomes contain large regions of satellite DNA. These arrays are often associated with essential chromosomal functions, but remain largely absent from genome projects because of difficulties in cloning and sequence assembly. The numerous small chromosomes of the parasite Trypanosoma brucei fall into this category, yet are critical to understanding the genome because of their role in antigenic variation. Their relatively small size, however, makes them particularly amenable to physical mapping. We have produced fine-resolution maps of 17 complete minichromosomes and partial maps of two larger intermediate-sized chromosomes. This revealed a canonical structure shared by both chromosomal classes based around a large central core of 177-bp repeats. Around the core are variable-length genic regions, the lengths of which define chromosomal class. We show the core region to be a repetitive palindrome with a single inversion point common to all the chromosomes of both classes, suggesting a mechanism of genesis for these chromosomes. Moreover, palindromy appears to be a feature of (peri)centromeres in other species that can be easily overlooked. We propose that sequence inversion is one of the higher-order sequence motifs that confer chromosomal stability.

MeSH Terms
Animals Antigenic Variation/genetics Base Composition/genetics Base Sequence/genetics Cell Line, Transformed Chromosome Mapping Chromosomes/genetics Chromosomes, Artificial, Bacterial/genetics Databases, Genetic Gene Duplication Molecular Sequence Data Repetitive Sequences, Nucleic Acid/genetics Trypanosoma brucei brucei/genetics
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Wickstead Bill
Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, United Kingdom.
Ersfeld Klaus
Gull Keith
References (70)
70 references, click to expand
  1. Neocentromeres in 15q24-26 map to duplicons which flanked an ancestral centromere in 15q25.
    Genome Res. 2003 Sep;13(9):2059-68 PMID: 12915487
  2. The mitotic stability of the minichromosomes of Trypanosoma brucei.
    Mol Biochem Parasitol. 2003 Dec;132(2):97-100 PMID: 14599670
  3. The macronuclear ribosomal DNA of Tetrahymena pyriformis is a palindrome.
    J Mol Biol. 1976 Jun 25;104(2):421-53 PMID: 820863
  4. Free ribosomal DNA molecules from Tetrahymena pyriformis GL are giant palindromes.
    J Mol Biol. 1976 Jun 25;104(2):455-70 PMID: 820864
  5. Structure of ribosomal DNA in Physarum polycephalum.
    J Mol Biol. 1976 Sep 25;106(3):567-87 PMID: 988186
  6. Dictyostelium rDNA consists of non-chromosomal palindromic dimers containing 5S and 36S coding regions.
    Chromosoma. 1978 Dec 21;70(1):19-29 PMID: 738167
  7. Cultivation and in vitro cloning or procyclic culture forms of Trypanosoma brucei in a semi-defined medium. Short communication.
    Acta Trop. 1979 Sep;36(3):289-92 PMID: 43092
  8. Characterization of satellite DNA in Trypanosoma brucei and Trypanosoma cruzi.
    J Mol Biol. 1983 Jun 15;167(1):1-21 PMID: 6345792
  9. Size fractionation of Trypanosoma brucei DNA: localization of the 177-bp repeat satellite DNA and a variant surface glycoprotein gene in a mini-chromosomal DNA fraction.
    Nucleic Acids Res. 1983 Jun 25;11(12):3889-901 PMID: 6866765
  10. Unstable DNA amplifications in methotrexate-resistant Leishmania consist of extrachromosomal circles which relocalize during stabilization.
    Cell. 1984 Sep;38(2):431-9 PMID: 6467372
  11. A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands.
    Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1827-31 PMID: 1542678
  12. A ribosomal RNA gene promoter at the telomere of a mini-chromosome in Trypanosoma brucei.
    Nucleic Acids Res. 1992 Jun 11;20(11):2725-34 PMID: 1319572
  13. Autonomously replicating single-copy episomes in Trypanosoma brucei show unusual stability.
    EMBO J. 1993 Jun;12(6):2529-38 PMID: 8508776
  14. The major centromeric array of alphoid satellite DNA on the human Y chromosome is non-palindromic.
    Hum Mol Genet. 1993 Aug;2(8):1267-70 PMID: 8401508
  15. Identification of a new expression site-associated gene in the complete 30.5 kb sequence from the AnTat 1.3A variant surface protein gene expression site of Trypanosoma brucei.
    Mol Biochem Parasitol. 1993 Nov;62(1):135-7 PMID: 8114817
  16. Long DNA palindromes, cruciform structures, genetic instability and secondary structure repair.
    Bioessays. 1994 Dec;16(12):893-900 PMID: 7840768
  17. Inducible gene expression in trypanosomes mediated by a prokaryotic repressor.
    Science. 1995 May 26;268(5214):1179-83 PMID: 7761835
  18. Common structural features of replication origins in all life forms.
    J Cell Biochem. 1996 Mar 1;60(3):297-316 PMID: 8867806
  19. Induction of large DNA palindrome formation in yeast: implications for gene amplification and genome stability in eukaryotes.
    Cell. 1996 Dec 13;87(6):1115-22 PMID: 8978615
  20. Genomic instability and its role in neoplasia.
    Curr Top Microbiol Immunol. 1997;221:37-46 PMID: 8979439
  21. Partitioning of large and minichromosomes in Trypanosoma brucei.
    Science. 1997 Apr 25;276(5312):611-4 PMID: 9110983
  22. A transposon-based strategy for sequencing repetitive DNA in eukaryotic genomes.
    Genome Res. 1997 May;7(5):551-63 PMID: 9149950
  23. Regulatory sequences for the amplification and replication of the ribosomal DNA minichromosome in Tetrahymena thermophila.
    Mol Cell Biol. 1997 Dec;17(12):7237-47 PMID: 9372956
  24. Tandem 5'-GA:GA-3' mismatches account for the high stability of the fold-back structures formed by the centromeric Drosophila dodeca-satellite.
    J Mol Biol. 1998 Apr 10;277(4):757-62 PMID: 9545369
  25. Centromeres take flight: alpha satellite and the quest for the human centromere.
    Cell. 1998 May 1;93(3):317-20 PMID: 9590164
  26. The molecular karyotype of the megabase chromosomes of Trypanosoma brucei and the assignment of chromosome markers.
    Mol Biochem Parasitol. 1998 Aug 1;94(2):155-73 PMID: 9747967
  27. Segregation of minichromosomes in trypanosomes: implications for mitotic mechanisms.
    Trends Microbiol. 1998 Aug;6(8):319-23 PMID: 9746942
  28. Urea improves efficiency of bisulphite-mediated sequencing of 5'-methylcytosine in genomic DNA.
    Nucleic Acids Res. 1998 Nov 1;26(21):5009-10 PMID: 9776768
  29. Genome sequence of the nematode C. elegans: a platform for investigating biology.
    Science. 1998 Dec 11;282(5396):2012-8 PMID: 9851916
  30. Initiation of DNA replication in eukaryotes: questioning the origin.
    FEBS Lett. 1999 Jun 4;452(1-2):87-91 PMID: 10376684
  31. Conserved DNA structures in origins of replication.
    Nucleic Acids Res. 1990 Mar 25;18(6):1609-12 PMID: 2326199
  32. Classes of autonomously replicating sequences are found among early-replicating monkey DNA.
    Biochim Biophys Acta. 1991 Feb 16;1088(2):234-44 PMID: 2001398
  33. Targeting, disruption, replacement, and allele rescue: integrative DNA transformation in yeast.
    Methods Enzymol. 1991;194:281-301 PMID: 2005793
  34. Stable integrative transformation of Trypanosoma brucei that occurs exclusively by homologous recombination.
    Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2118-21 PMID: 2006150
  35. Chromosome structure: DNA nucleotide sequence elements of a subset of the minichromosomes of the protozoan Trypanosoma brucei.
    Mol Cell Biol. 1991 Aug;11(8):3823-34 PMID: 2072894
  36. Short inverted repeats at a free end signal large palindromic DNA formation in Tetrahymena.
    Cell. 1991 Nov 1;67(3):505-16 PMID: 1934058
  37. Neocentromeres and alpha satellite: a proposed structural code for functional human centromere DNA.
    Hum Mol Genet. 2000 Jan 22;9(2):149-54 PMID: 10607825
  38. The genome sequence of Drosophila melanogaster.
    Science. 2000 Mar 24;287(5461):2185-95 PMID: 10731132
  39. The African trypanosome genome.
    Int J Parasitol. 2000 Apr 10;30(4):329-45 PMID: 10731558
  40. Centromerization.
    Trends Cell Biol. 2000 May;10(5):182-8 PMID: 10754560
  41. Inverted Alu repeats unstable in yeast are excluded from the human genome.
    EMBO J. 2000 Jul 17;19(14):3822-30 PMID: 10899135
  42. Structure-function relationships in replication origins of the yeast Saccharomyces cerevisiae: higher-order structural organization of DNA in regions flanking the ARS consensus sequence.
    Mol Gen Genet. 2000 Jun;263(5):854-66 PMID: 10905353
  43. Tandemly repeated DNA is a target for the partial replacement of thymine by beta-D-glucosyl-hydroxymethyluracil in Trypanosoma brucei.
    Mol Biochem Parasitol. 2000 Jul;109(2):133-45 PMID: 10960172
  44. Analysis of the genome sequence of the flowering plant Arabidopsis thaliana.
    Nature. 2000 Dec 14;408(6814):796-815 PMID: 11130711
  45. Initial sequencing and analysis of the human genome.
    Nature. 2001 Feb 15;409(6822):860-921 PMID: 11237011
  46. Diversity and dynamics of the minichromosomal karyotype in Trypanosoma brucei.
    Mol Biochem Parasitol. 2001 Mar;113(1):79-88 PMID: 11254956
  47. A telomere-mediated chromosome fragmentation approach to assess mitotic stability and ploidy alterations of Leishmania chromosomes.
    J Biol Chem. 2001 Apr 13;276(15):11662-73 PMID: 11152684
  48. Antigenic variation in trypanosomes: enhanced phenotypic variation in a eukaryotic parasite.
    Adv Parasitol. 2001;49:1-70 PMID: 11461029
  49. Effect of large targeted deletions on the mitotic stability of an extra chromosome mediating drug resistance in Leishmania.
    Nucleic Acids Res. 2001 Aug 1;29(15):3231-40 PMID: 11470881
  50. Determining centromere identity: cyclical stories and forking paths.
    Nat Rev Genet. 2001 Aug;2(8):584-96 PMID: 11483983
  51. The centromere paradox: stable inheritance with rapidly evolving DNA.
    Science. 2001 Aug 10;293(5532):1098-102 PMID: 11498581
  52. The centromere1 (CEN1) region of Arabidopsis thaliana: architecture and functional impact of chromatin.
    Plant J. 2001 Aug;27(4):285-96 PMID: 11532174
  53. Genomic and genetic definition of a functional human centromere.
    Science. 2001 Oct 5;294(5540):109-15 PMID: 11588252
  54. Conserved organization of centromeric chromatin in flies and humans.
    Dev Cell. 2002 Mar;2(3):319-30 PMID: 11879637
  55. Mitotic stability of a coding DNA sequence-free version of Leishmania major chromosome 1 generated by targeted chromosome fragmentation.
    Gene. 2002 May 1;289(1-2):151-9 PMID: 12036593
  56. Short inverted repeats initiate gene amplification through the formation of a large DNA palindrome in mammalian cells.
    Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8772-7 PMID: 12060719
  57. The architecture of variant surface glycoprotein gene expression sites in Trypanosoma brucei.
    Mol Biochem Parasitol. 2002 Jul;122(2):131-40 PMID: 12106867
  58. Neocentromeres: role in human disease, evolution, and centromere study.
    Am J Hum Genet. 2002 Oct;71(4):695-714 PMID: 12196915
  59. Targeting of a tetracycline-inducible expression system to the transcriptionally silent minichromosomes of Trypanosoma brucei.
    Mol Biochem Parasitol. 2002 Nov-Dec;125(1-2):211-6 PMID: 12467990
  60. Sequence analysis of a functional Drosophila centromere.
    Genome Res. 2003 Feb;13(2):182-94 PMID: 12566396
  61. Sequence and structure of the extrachromosomal palindrome encoding the ribosomal RNA genes in Dictyostelium.
    Nucleic Acids Res. 2003 May 1;31(9):2361-8 PMID: 12711681
  62. The frequency of gene targeting in Trypanosoma brucei is independent of target site copy number.
    Nucleic Acids Res. 2003 Jul 15;31(14):3993-4000 PMID: 12853615
  63. The sequence and analysis of Trypanosoma brucei chromosome II.
    Nucleic Acids Res. 2003 Aug 15;31(16):4856-63 PMID: 12907728
  64. The DNA sequence of chromosome I of an African trypanosome: gene content, chromosome organisation, recombination and polymorphism.
    Nucleic Acids Res. 2003 Aug 15;31(16):4864-73 PMID: 12907729
  65. Multiple causes of size variation in the diploid megabase chromosomes of African tyrpanosomes.
    Chromosome Res. 1999;7(3):191-203 PMID: 10421379
  66. Predominance of duplicative VSG gene conversion in antigenic variation in African trypanosomes.
    Mol Cell Biol. 1999 Sep;19(9):5839-46 PMID: 10454531
  67. Long range cooperative interactions regulate the initiation of replication in the Tetrahymena thermophila rDNA minichromosome.
    Nucleic Acids Res. 1999 Aug 1;27(15):3079-89 PMID: 10454603
  68. Clustered adenine/thymine stretches are essential for function of a fission yeast replication origin.
    Mol Cell Biol. 1999 Oct;19(10):6699-709 PMID: 10490609
  69. Large inverted duplications are associated with gene amplification.
    Cell. 1986 May 9;45(3):425-30 PMID: 2870814
  70. Resistance to antimycin A in yeast by amplification of ADH4 on a linear, 42 kb palindromic plasmid.
    Cell. 1986 Sep 12;46(6):857-63 PMID: 3019553
Article Info
Journal
Genome research
Abbr.
Genome Res
ISSN
1088-9051
DOI
10.1101/gr.2227704
Published
2004-06-00
Pages
1014-24
Language
English
Region
United States
NLM ID
9518021
PMCID
PMC419779
Subset
IM
External Links
PubMed source DOI: 10.1101/gr.2227704 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2