Global Microsatellite Content Potentially Distinguishes Humans, Primates, Animals, and Plants

Microsatellites are highly mutable, repetitive sequences commonly used as genetic markers, but they have never been assayed en masse. Using a custom microarray to measure hybridization intensities of every possible repetitive nucleotide motif from 1-mers to 6-mers, we examined 25 genomes. Here we show that global microsatellite content, as measured by array hybridization signal intensities, independently validates data from published sequence databases and is a sensitive and specific gauge of mutation in an in vitro model of microsatellite instability, an MLH1 knockout (RKO6) cell line. Moreover, we demonstrate that microsatellite content varies predictably by species, and that particular motifs are characteristic of one species versus another. For instance, hominid-specific microsatellite motifs were identified despite alignment of the human reference, Celera, and Venter genomic sequences indicating substantial variation (30-50%) among individuals. Differential microsatellite motifs were mainly associated with genes involved in developmental processes, while those found in intergenic regions exhibited no discernible pattern related to transcription factor binding sites or non-microsatellite repetitive sequences (i.e., LINEs, and SINEs). This is the first description of a method for evaluating microsatellite content to classify individual genomes.