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Genetics, Vol. 168, 383-395, September 2004, Copyright © 2004
doi:10.1534/genetics.103.022665
Microsatellite Mutation Models
Insights From a Comparison of Humans and Chimpanzees
Raazesh Sainudiin*,1,
Richard T. Durrett
,
Charles F. Aquadro
and
Rasmus Nielsen
* Department of Statistical Science, Cornell University, Ithaca, New York 14853
Department of Mathematics, Cornell University, Ithaca, New York 14853
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853
Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York 14853
1 Corresponding author: Department of Statistical Science, 301 Malott Hall, Cornell University, Ithaca, NY 14853.
E-mail: rs228{at}cornell.edu
Using genomic data from homologous microsatellite loci of pure AC repeats in humans and chimpanzees, several models of microsatellite evolution are tested and compared using likelihood-ratio tests and the Akaike information criterion. A proportional-rate, linear-biased, one-phase model emerges as the best model. A focal length toward which the mutational and/or substitutional process is linearly biased is a crucial feature of microsatellite evolution. We find that two-phase models do not lead to a significantly better fit than their one-phase counterparts. The performance of models based on the fit of their stationary distributions to the empirical distribution of microsatellite lengths in the human genome is consistent with that based on the human-chimp comparison. Microsatellites interrupted by even a single point mutation exhibit a twofold decrease in their mutation rate when compared to pure AC repeats. In general, models that allow chimps to have a larger per-repeat unit slippage rate and/or a shorter focal length compared to humans give a better fit to the human-chimp data as well as the human genomic data.
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