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The structure and evolution of centromeric transition regions within the human genome


An understanding of how centromeric transition regions are organized is a critical aspect of chromosome structure and function; however, the sequence context of these regions has been difficult to resolve on the basis of the draft genome sequence. We present a detailed analysis of the structure and assembly of all human pericentromeric regions (5 megabases). Most chromosome arms (35 out of 43) show a gradient of dwindling transcriptional diversity accompanied by an increasing number of interchromosomal duplications in proximity to the centromere. At least 30% of the centromeric transition region structure originates from euchromatic gene-containing segments of DNA that were duplicatively transposed towards pericentromeric regions at a rate of six–seven events per million years during primate evolution. This process has led to the formation of a minimum of 28 new transcripts by exon exaptation and exon shuffling, many of which are primarily expressed in the testis. The distribution of these duplicated segments is nonrandom among pericentromeric regions, suggesting that some regions have served as preferential acceptors of euchromatic DNA.

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Figure 1: Models of centromeric transition regions.
Figure 2: Pericentromeric architecture.
Figure 3: Sequence properties of centromeric transition regions.
Figure 4: Cohorts of pericentromeric duplication.
Figure 5: Ancestral duplicons within 2p11.


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We are grateful to the large-scale sequencing centres (Baylor College of Medicine, Cold Spring Harbor Laboratory, Genome Therapeutics Corporation, Harvard Partners Genome Center, Joint Genome Institute, The NIH Intramural Sequencing Center, The UK-MRC Sequencing Consortium, The University of Oklahoma Advanced Center for Genome Technology, The University of Texas Southwest, The Whitehead Institute for Biomedical Research, The Washington University Genome Sequencing Center and the Wellcome Trust Sanger Institute) for access to all large-scale finished sequence, genome assembly and trace sequence data from the human genome before publication. This work was supported by grants from NIH and DOE to E.E.E. and grants from P.R.I.N.C.E., MURST and Telethon to M.R.

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Corresponding author

Correspondence to Evan E. Eichler.

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The authors declare that they have no competing financial interests.

Supplementary information

Supplementary Methods

This file includes a detailed description of the Methods and additional references. (DOC 63 kb)

Supplementary Table 1a

Gaps, repeats and exons within 2Mb pericentromeric regions. (XLS 24 kb)

Supplementary Table 1b

Gaps, repeats and exons within 5Mb pericentromeric regions. (XLS 22 kb)

Supplementary Table 1c

Duplications and pairwise alignments within 2Mb pericentromeric regions. (XLS 31 kb)

Supplementary Table 1d

Duplications and pairwise alignments within 5Mb pericentromeric regions. (XLS 28 kb)

Supplementary Table 1e

Homology between each 2Mb pericentromeric region and all other chromosomes. (XLS 30 kb)

Supplementary Table 1f

Homology between each 5Mb pericentromeric region and all other chromosomes. (XLS 32 kb)

Supplementary Table 2

Analysis of alpha satellite DNA placement in build 34 (July 2003) for each chromosome. (XLS 29 kb)

Supplementary Table 3

Cytogenetic vs. in silico analysis of human alpha-satellite containing sequences. (XLS 23 kb)

Supplementary Table 4

Assessment of all gaps within the finished human genome. (XLS 19 kb)

Supplementary Table 5

Complete analysis of cytogenetic vs. in silico analysis of human segmental duplications. (XLS 116 kb)

Supplementary Table 6

Brief summary of cytogenetic vs. in silico analysis of human segmental duplications. (XLS 16 kb)

Supplementary Table 7

Paralogous STS content of 10 pericentromeric duplicons in the human genome. (XLS 18 kb)

Supplementary Table 8

Duplicon junction analysis. (XLS 19 kb)

Supplementary Table 9

Non-human primate mapping of pericentromeric duplications on 2p11. (XLS 17 kb)

Supplementary Table 10

Summary of ancestral duplicons and corresponding gene composition. (XLS 80 kb)

Supplementary Table 11a

Refseq genes located within 2Mb pericentromeric regions. (XLS 81 kb)

Supplementary Table 11b

Refseq genes located within 5Mb pericentromeric regions. (XLS 241 kb)

Supplementary Table 12

Known genes and mRNAs within pericentromeric duplications from ancestral donors. (XLS 29 kb)

Supplementary Table 13

RT-PCR analysis of a subset of pericentromeric genes, mRNAs and ESTs. (XLS 28 kb)

Supplementary Figure 1a

Repeat density plotted within 10Mb pericentromeric regions. (PDF 28 kb)

Supplementary Figure 1b

Exon density plotted within 10Mb pericentromeric regions. (PDF 358 kb)

Supplementary Figure 2

The 20 largest pericentromeric-pericentromeric alignments within 2Mb pericentromeric regions. (PDF 39 kb)

Supplementary Figure 3

Distribution of pericentromeric duplications for each chromosome by divergence. (PDF 651 kb)

Supplementary Figure 4

Methodology for identification of ancestral duplicons using mousenet. (PDF 26 kb)

Supplementary Figure 5

Ancestral duplicons within 15q11. (PDF 108 kb)

Supplementary Figure 6

Sequence similarity between acceptor duplicons and donor duplicons. (PDF 97 kb)

Supplementary Figure 7

Sequence structure of genes and mRNAs within pericentromeric regions. (PDF 287 kb)

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She, X., Horvath, J., Jiang, Z. et al. The structure and evolution of centromeric transition regions within the human genome. Nature 430, 857–864 (2004).

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