Heterozygosity Increases Microsatellite Mutation Rate, Linking it to Demographic History

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Heterozygosity Increases Microsatellite Mutation Rate, Linking it to Demographic History

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Title: Heterozygosity Increases Microsatellite Mutation Rate, Linking it to Demographic History
Author: Amos, William; Flint, Jonathan; Xu, Xin

Note: Order does not necessarily reflect citation order of authors.

Citation: Amos, William, Jonathan Flint, and Xin Xu. 2008. Heterozygosity increases microsatellite mutation rate, linking it to demographic history. BMC Genetics 9:72.
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Abstract: Background: Biochemical experiments in yeast suggest a possible mechanism that would cause heterozygous sites to mutate faster than equivalent homozygous sites. If such a process operates, it could undermine a key assumption at the core of population genetic theory, namely that mutation rate and population size are indpendent, because population expansion would increase heterozygosity that in turn would increase mutation rate. Here we test this hypothesis using both direct counting of microsatellite mutations in human pedigrees and an analysis of the relationship between microsatellite length and patterns of demographically-induced variation in heterozygosity. Results: We find that microsatellite alleles of any given length are more likely to mutate when their homologue is unusually different in length. Furthermore, microsatellite lengths in human populations do not vary randomly, but instead exhibit highly predictable trends with both distance from Africa, a surrogate measure of genome-wide heterozygosity, and modern population size. This predictability remains even after statistically controlling for non-independence due to shared ancestry among populations. Conclusion: Our results reveal patterns that are unexpected under classical population genetic theory, where no mechanism exists capable of linking allele length to extrinsic variables such as geography or population size. However, the predictability of microsatellite length is consistent with heterozygote instability and suggest that this has an important impact on microsatellite evolution. Whether similar processes impact on single nucleotide polymorphisms remains unclear.
Published Version: doi:10.1186/1471-2156-9-72
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2615044/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:4556381
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