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EVOLUTION
Quantifying the mechanisms for segmental duplications in mammalian genomes by statistical analysis and modeling

Yi Zhou ^*, , and Bud Mishra ^, , 

^*Department of Biology, Courant Institute of Mathematical Sciences, and School of Medicine, New York University, New York, NY 10003

Edited by Charles R. Cantor, Sequenom, Inc., San Diego, CA, and approved January 19, 2005 (received for review October 26, 2004)

A large number of the segmental duplications in mammalian genomes have been cataloged by genome-wide sequence analyses. The molecular mechanisms involved in these duplications mostly remain a matter of speculation. To uncover, test, and further quantify the hypotheses on the mechanisms for the recent duplications in the mammalian genomes, we have performed a series of statistical analyses on the sequences flanking the duplicated segments and proposed a dynamic model for the duplication process. The model, when applied to the human duplication data, indicates that 30% of the recent human segmental duplications were caused by a recombination-like mechanism, among which 12% were mediated by the most recently active repeat, Alu. But a significant proportion of the duplications are caused by some mechanism independent of the repeat distribution. A less sure but similar picture is found in the rodent genomes. A further analysis on the physical features of the flanking sequences suggests that one of the uncharacterized duplication mechanisms shared by the mammalian genomes is surprisingly well correlated with the physical instability in the DNA sequences.

segmental duplication | genomic instability | interspersed transposable elements | Markov models | copy number fluctuation

This paper was submitted directly (Track II) to the PNAS office.

Abbreviation: L1, long interspersed transposable element 1.

To whom correspondence should be addressed at: NYU Bioinformatics Group, New York University, 715 Broadway, Room 1002, New York, NY 10003. E-mail: mishra{at}nyu.edu.

© 2005 by The National Academy of Sciences of the USA

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