Low microsatellite frequencies in neuron and brain expressed microRNAs

Area of Science:

• Genomics
• Molecular Biology
• Evolutionary Biology

Background:

• Microsatellites are repetitive DNA sequences found throughout mammalian genomes.
• Purifying selection typically removes deleterious mutations, influencing microsatellite distribution and types.
• MicroRNAs (miRNAs) are small non-coding RNAs crucial for gene regulation, with some expressed in neurons and the brain (NB-miRNAs).

Purpose of the Study:

• To investigate if purifying selection affects the types and frequencies of microsatellites within miRNA genes.
• To specifically examine microsatellite patterns in NB-miRNAs due to their potential to cause disease-like effects.
• To determine if NB-miRNAs exhibit different microsatellite constraints compared to other miRNAs.

Main Methods:

• Comparative analysis of microsatellite frequencies (AG, AT, AC repeats) in human miRNAs.
• Quantification of microsatellite content in NB-miRNA genes versus other miRNA genes.
• Assessment of sequence divergence and orthologue detection in mammalian species for NB-miRNAs and non-NB-miRNAs.

Main Results:

• AG and AT microsatellites are less frequent than AC repeats in human miRNAs.
• NB-miRNA genes have significantly fewer microsatellites than expected based on other miRNA genes.
• NB-miRNAs display lower sequence divergence and higher orthologue conservation across mammals.

Conclusions:

• Microsatellites in miRNAs appear to be under purifying selection, with potential disruption of pre-miRNA secondary structure as a mechanism.
• The strength of purifying selection on microsatellites may vary between NB-miRNAs and non-NB-miRNAs.
• Non-selective forces might also contribute to observed biases in miRNA microsatellite composition.