Low microsatellite frequencies in neuron and brain expressed microRNAs

Abstract

The locations of microsatellites in mammalian genomes are restricted by purifying selection in a number of ways. For example, with the exception of some trinucleotide repeats they are excluded from protein coding regions of genomes because of their tendency to cause frameshift mutations. Here we investigate whether purifying selection might affect the types and frequencies of microsatellites in microRNA (miRNA). We concentrate on miRNAs expressed in neurons and the brain (NB-miRNAs) as microsatellites in these genes might give rise to similar effects as disease-causing repeats in protein coding genes. We show that in human miRNAs in general AG and AT microsatellites are reduced in frequency compared to AC repeats and that NB-miRNA genes contain significantly fewer microsatellites than expected from frequencies of microsatellites in other miRNA genes. NB-miRNAs show lower levels of sequence divergence in comparisons of human-macaque orthologues and more often have detectable orthologues in non-human mammals than non-NB-miRNAs. This suggests that microsatellites in miRNAs may indeed be constrained by purifying selection and that the strength of this selection may differ between NB-miRNAs and non-NB-miRNAs. We identify a number of ways in which the potential disruption of pre-miRNA secondary structure might result in purifying selection. However other, non-selective forces could also play a role in generating the biases observed in miRNA microsatellites.