MBE Advance Access published online on September 15, 2008
Molecular Biology and Evolution, doi:10.1093/molbev/msn201
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The relationship between microsatellite polymorphism and recombination hotspots in the human genome
1 Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Sweden
2 School of Biological Sciences, University of Canterbury, New Zealand
3 Current address: Department of Forest Mycology and Pathology, Swedish University of Agricultural Sciences, Sweden
4 Current address: Otago School of Medical Sciences, University of Otago, New Zealand
Correspondence: Prof Hans Ellegren, Dept of Evolutionary Biology, Uppsala University, Norbyvägen 18D, SE-752 36 Uppsala, Sweden, Email: Hans.Ellegren{at}ebc.uu.se, Fax: +46-18-4716310, Phone: +46-18-4716460
Received for publication August 7, 2008. Revision received August 31, 2008. Accepted for publication September 1, 2008.
Although previous studies have failed to detect an association between microsatellite polymorphism and broad-scale recombination rates in the human genome, there are several possible reasons why such a relationship could exist. For instance, there might be a direct link if recombination is mutagenic to microsatellite sequences or if polymorphic microsatellites act as recombination signals. Alternatively, recombination could exert an indirect effect by uncoupling of natural selection at linked loci, promoting polymorphism. As recombination is concentrated in narrow hotspot regions in the human genome, we investigated the relationship between microsatellite polymorphism and recombination hotspots. By using data from a common allele frequency database, we found several polymorphism estimates to be similar for hotspots and the genomic average. However, this is likely explained by an ascertainment bias since markers with high polymorphism information content are usually selected for genotyping in human populations and pedigrees. In contrast, by using an unbiased set of shotgun sequence data we found an excess of microsatellite polymorphism in recombination hotspots of 14%. However, when other genomic variables are taken into account in a generalized model and using wavelet analysis, the effect is no longer detectable and the only firm predictor of microsatellite polymorphism is the incidence of SNPs and indels. One possible neutral explanation to these observations is that there is a common denominator affecting the local rate of mutation in unique as well as in repetitive DNA, for example, base composition.