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Genome Biol. 2008;9(7):R105. doi: 10.1186/gb-2008-9-7-r105. Epub 2008 Jul 3.

Asymmetric histone modifications between the original and derived loci of human segmental duplications.

Author information

  • Institute for Brain Disorders and Neural Regeneration, The Saul R, Korey Department of Neurology, Albert Einstein College of Medicine, Rose F, Kennedy Center 915B, 1410 Pelham Parkway South, Bronx, NY 10461, USA. dzheng@aecom.yu.edu

Abstract

BACKGROUND:

Sequencing and annotation of several mammalian genomes have revealed that segmental duplications are a common architectural feature of primate genomes; in fact, about 5% of the human genome is composed of large blocks of interspersed segmental duplications. These segmental duplications have been implicated in genomic copy-number variation, gene novelty, and various genomic disorders. However, the molecular processes involved in the evolution and regulation of duplicated sequences remain largely unexplored.

RESULTS:

In this study, the profile of about 20 histone modifications within human segmental duplications was characterized using high-resolution, genome-wide data derived from a ChIP-Seq study. The analysis demonstrates that derivative loci of segmental duplications often differ significantly from the original with respect to many histone methylations. Further investigation showed that genes are present three times more frequently in the original than in the derivative, whereas pseudogenes exhibit the opposite trend. These asymmetries tend to increase with the age of segmental duplications. The uneven distribution of genes and pseudogenes does not, however, fully account for the asymmetry in the profile of histone modifications.

CONCLUSION:

The first systematic analysis of histone modifications between segmental duplications demonstrates that two seemingly 'identical' genomic copies are distinct in their epigenomic properties. Results here suggest that local chromatin environments may be implicated in the discrimination of derived copies of segmental duplications from their originals, leading to a biased pseudogenization of the new duplicates. The data also indicate that further exploration of the interactions between histone modification and sequence degeneration is necessary in order to understand the divergence of duplicated sequences.

PMID:
18598352
[PubMed - indexed for MEDLINE]
PMCID:
PMC2530858
Free PMC Article

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