Microsatellite repeats: Canaries in the coalmine

Abstract

Our genomes are much more dynamic than we ever imagined, creating variation that is good for evolution, but often bad for the individual. Microsatellite repeats constitute especially plastic genomic elements that can operate as rheostats to fine-tune gene function. Microsatellite repeats mutate at high frequency in predictable ways, and the mutations can confer incremental changes on the activities of gene regulatory elements and encoded proteins. The downside of microsatellite instability is highlighted by a collection of human diseases that are caused by expansion of microsatellite repeats. Studies with disease-associated trinucleotide repeats (TNRs) reveal that changes in DNA methylation, transcription, and the Hsp90 chaperone increase the mutation rates of TNRs. The observation that environmental stress can alter epigenetic marks, transcription rates, and Hsp90 activity raises the possibility that stress modifies the mutation rates of microsatellite repeats. Thus, microsatellite repeats may behave as genomic detectors of environmental stress.