MBE Advance Access published online on March 5, 2003
Molecular Biology and Evolution, doi:10.1093/molbev/msg056
Molecular Biology and Evolution © Society for Molecular Biology and Evolution 2003; all rights reserved
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1 School of Animal and Microbial Sciences, University of Reading RG6 6AJ, UK
* To whom correspondence should be addressed. E-mail: r.m.sibly{at}rdg.ac.uk.
Microsatellite lengths change over evolutionary time through a process of replication slippage. A recently proposed model of this process holds that the expansionary tendencies of slippage mutation are balanced by point mutations breaking longer microsatellites into smaller units, and that this process gives rise to the observed frequency distributions of uninterrupted microsatellite lengths. We refer to this as the slippage/point-mutation theory. Here we derive the theory's predictions for interrupted microsatellites comprising regions of perfect repeats, labelled segments, separated by dinucleotide interruptions containing point mutations. These predictions are tested by reference to the frequency distributions of segments of AC microsatellite in the human genome and several predictions are shown to be not supported by the data, as follows. The estimated slippage rates are relatively low for the first 4 repeats, and then rise initially linearly with length, in accordance with previous work. However contrary to expectation and the experimental evidence, the inferred slippage rates decline in segments above 10 repeats. Point mutation rates are also found to be higher within microsatellites than elsewhere. The theory provides an excellent fit to the frequency distribution of peripheral segment lengths, but fails to explain why internal segments are shorter. Furthermore there are fewer microsatellites with many segments than predicted. The frequencies of interrupted microsatellites decline geometrically with microsatellite size measured in number of segments, so that for each additional segment the number of microsatellites is 33.6% less. Overall we conclude that the detailed structure of interrupted microsatellites cannot be reconciled with the existing slippage/point-mutation theory of microsatellite evolution, and suggest that microsatellites are stabilised by processes acting on interior rather than on peripheral segments. Key Words:
microsatellite evolution, replication slippage, dinucleotide repeats, human, AC
© 2003 Society for Molecular Biology and Evolution
Original Articles
The Structure of Interrupted Human AC Microsatellites
2 School of Animal and Microbial Sciences, University of Reading RG6 6AJ, UK; School of Computer Science, University of Reading RG6 6AJ, UK
3 School of Animal and Microbial Sciences, University of Reading RG6 6AJ, UK; Department of Applied Statistics, University of Reading RG6 6FN, UK
4 Department of Agricultural Botany, University of Reading RG6 6AS, UK
5 School of Computer Science, University of Reading RG6 6AJ, UK
6 Department of Applied Statistics, University of Reading RG6 6FN, UK
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