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Epigenetic Changes and Repositioning Determine the Evolutionary Fate of Duplicated Genes

S. N. Rodin, D. V. Parkhomchuk, and A. D. Riggs*

Department of Theoretical Biology, Beckman Research Institute of the City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USA; fax: 626-930-5366; E-mail: ariggs@coh.org

* To whom correspondence should be addressed.

Received December 4, 2004
Consideration of epigenetic silencing, perhaps by DNA methylation, led to an epigenetic complementation (EC) model for evolution by gene duplication (Rodin and Riggs (2003) J. Mol. Evol., 56, 718-729). This and subsequent work on genome-wide analyses of gene duplicates in several eukaryotic species pointed to a fundamental link between localization in the genome, epigenetic regulation of expression, and the evolutionary fate of new redundant gene copies, which can be either non- or neo-functionalization. Our main message in this report is that repositioning of a new duplicate to an ectopic site epigenetically alters its expression pattern, and concomitantly the rate and direction of mutations. Furthermore, comparison of syntenic vs. non-syntenic pairs of gene duplicates of different age unambiguously indicates that repositioning saves redundant gene duplicates from pseudogenization and hastens their evolution towards a new development-time and tissue-specific pattern of function.
KEY WORDS: DNA methylation, molecular evolution, comparative genomics, gene duplications, position effects, genetic complexity