Epigenetic Changes and Repositioning Determine the Evolutionary Fate of Duplicated Genes

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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

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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.

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KEY WORDS: DNA methylation, molecular evolution, comparative genomics, gene duplications, position effects, genetic complexity

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