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Human subtelomeres are hot spots of interchromosomal recombination and segmental duplication


Human subtelomeres are polymorphic patchworks of interchromosomal segmental duplications at the ends of chromosomes. Here we provide evidence that these patchworks arose recently through repeated translocations between chromosome ends. We assess the relative contribution of the principal mechanisms of ectopic DNA repair to the formation of subtelomeric duplications and find that non-homologous end-joining predominates. Once subtelomeric duplications arise, they are prone to homology-based sequence transfers as shown by the incongruent phylogenetic relationships of neighbouring sections. Interchromosomal recombination of subtelomeres is a potent force for recent change. Cytogenetic and sequence analyses reveal that pieces of the subtelomeric patchwork have changed location and copy number with unprecedented frequency during primate evolution. Half of the known subtelomeric sequence has formed recently, through human-specific sequence transfers and duplications. Subtelomeric dynamics result in a gene duplication rate significantly higher than the genome average and could have both advantageous and pathological consequences in human biology. More generally, our analyses suggest an evolutionary cycle between segmental polymorphisms and genome rearrangements.

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We are grateful to the many contributors to the Human Genome Project who generated the sequences that made this study possible, and to the Eichler and Haussler laboratory groups for making data on segmental duplications readily accessible. Our work was supported by the NIH. We thank E. Eichler, H. Malik, D. Gottschling, J. Gogarten, K. Rudd and M. Schlador for comments on the manuscript, and J. Felsenstein for advice on phylogenetic analyses.

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Correspondence to Barbara J. Trask.

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Reprints and permissions information is available at The authors declare no competing financial interests.

Supplementary information

Supplementary Methods

Detailed description of computational and experimental methods used in study and additional observations. (Includes references cited in Supplementary Tables S1-S11). (PDF 265 kb)

Supplmentary Tables S1-S11

Eleven supplementary tables, provided together in one pdf file. (PDF 536 kb)

Supplementary Figure S1

Diagram summarizing PCR analyses of a monochromosomal hybrid panel using 55 primer pairs distributed across subtelomeric regions. The results confirm block boundaries defined by available sequence and identify additional copies not yet represented in genome assembly. (PDF 445 kb)

Supplementary Figure S2

Diagram of an NAHR-medicated translocation leading to a homology breakpoint within subtelomeres. (PDF 709 kb)

Supplementary Figure S3

Diagram of one of three breakpoints with degenerate telomere repeats at the junction and undetermined mechanism. (PDF 203 kb)

Supplementary Figure S4

Diagram of deletion formed by non-allelic homologous recombination of Alu elements on either the same or different chromosomes. (PDF 595 kb)

Supplementary Figure S5

Multiple changes in the historical relationships among subtelomeric sequences are apparent in this diagram of the best matching pairs in 2-kbp windows across the multiple sequence alignment of a region shared by seven chromosomes. (PDF 94 kb)

Supplementary Figure S6

Close-up view of the gross disparity in subtelomeric content of two sequenced alleles of 16p. (PDF 100 kb)

Supplementary Figure S7

The distribution of the percent identity of all pairwise alignments of all subtelomeric blocks shows that most subtelomeric duplications are very recent. (PDF 64 kb)

Supplementary Figure S8

Diagram of the best match for each block in each subtelomeric contig illustrates the extensive regions created by recent exchange and their spatial arrangement. (PDF 250 kb)

Supplementary Data

Sequences of representative copies of each block in fasta format. (TXT 883 kb)

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Further reading

Figure 1: Subtelomeric paralogy map.
Figure 2: A translocation-based model of segmental duplication and polymorphism.
Figure 3: Layers of interchromosomal translocations form subtelomeric blocks.
Figure 4: Most subtelomeric homology breakpoints are consistent with NHEJ.
Figure 5: Homology-based sequence transfers between subtelomeres.
Figure 6: Chromosomal distribution of four subtelomeric blocks.


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