Genome-wide analysis of microsatellite polymorphism circumventing the ascertainment bias
Abstract
Studies of microsatellites evolution based on marker data almost inherently suffer from an ascertainment bias because there is selection for the most mutable and polymorphic loci during marker development. To circumvent this bias we took the advantage of whole-genome shot-gun sequence data from three unrelated chicken individuals that, when aligned to the genome reference sequence, give sequence information on two chromosomes from about half (390,000) of all microsatellite loci containing di- through pentanucleotide repeat motifs in the chicken genome. Polymorphism is seen at loci with as few as five repeat units and the proportion of dimorphic loci then increases to 50% for sequences with about 10 repeat units, to reach a maximum of 75-80% for sequences with 15 or more repeat units. For any given repeat length, polymorphism increases with decreasing GC content of repeat motifs for dinucleotides, non-hairpin forming trinucleotides and tetranucleotides. For trinucleotide repeats which are likely to form hairpin structures, polymorphism increases with increasing GC content, indicating that the relative stability of hairpins affects the rate of replication slippage. For any given repeat length, polymorphism is significantly lower for imperfect compared to perfect repeats and repeat interruptions occur in more than 15% of loci. However, interruptions are not randomly distributed within repeat arrays but are preferentially located towards the ends. There is negative correlation between microsatellite abundance and SNP density, providing large-scale genomic support for the hypothesis that equilibrium microsatellite distributions are governed by a balance between rate of replication slippage and rate of point mutation.
Footnotes
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- Received December 5, 2007.
- Accepted March 11, 2008.
- Copyright © 2008, Cold Spring Harbor Laboratory Press
