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Published online before print December 19, 2005, 10.1101/gr.4456006
Genome Res. 16:173-181, 2006
©2006 by Cold Spring Harbor Laboratory Press; ISSN 1088-9051/06 $5.00
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Letter

Identification by full-coverage array CGH of human DNA copy number increases relative to chimpanzee and gorilla

Gary M. Wilson1, Stephane Flibotte1, Perseus I. Missirlis1, Marco A. Marra1, Steven Jones1, Kevin Thornton2, Andrew G. Clark2 and Robert A. Holt1,3

1 Canada's Michael Smith Genome Sciences Centre, Vancouver, BC, Canada V5Z 4S6 2 Cornell University, Ithaca, New York 14853, USA

Duplication of chromosomal segments and associated genes is thought to be a primary mechanism for generating evolutionary novelty. By comparative genome hybridization using a full-coverage (tiling) human BAC array with 79-kb resolution, we have identified 63 chromosomal segments, ranging in size from 0.65 to 1.3 Mb, that have inferred copy number increases in human relative to chimpanzee. These segments span 192 Ensembl genes, including 82 gene duplicates (41 reciprocal best BLAST matches). Synonymous and nonsynonymous substitution rates across these pairs provide evidence for general conservation of the amino acid sequence, consistent with the maintenance of function of both copies, and one case of putative positive selection for an uncharacterized gene. Surprisingly, the core histone genes H2A, H2B, H3, and H4 have been duplicated in the human lineage since our split with chimpanzee. The observation of increased copy number of a human cluster of core histone genes suggests that altered dosage, even of highly constrained genes, may be an important evolutionary mechanism.

Article published online ahead of print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.4456006.

3 Corresponding author.
E-mail rholt{at}bcgsc.ca; fax (604) 877-6085.

[Supplemental material is available online at www.genome.org.]


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