Human polymorphism at microRNAs and microRNA target sites

Area of Science:

• Genomics
• Molecular Biology
• Evolutionary Biology

Background:

• MicroRNAs (miRNAs) are crucial regulators of gene expression, primarily by binding to messenger RNA (mRNA) targets.
• Single nucleotide polymorphisms (SNPs) within miRNA binding sites can alter gene regulation, potentially impacting phenotypes.
• Human variation in miRNAs and their target sites remains largely uncharacterized.

Purpose of the Study:

• To investigate the extent of genetic variation, specifically SNPs, within human microRNA genes and their target sites.
• To identify SNPs that may affect miRNA binding and gene regulation.
• To explore the evolutionary implications of variation at miRNA target sites.

Main Methods:

• Analysis of publicly available human SNP data.
• Integration of SNP data with genomic locations of microRNAs and their predicted/verified target sites.
• Assessment of evolutionary conservation and population frequencies of identified SNPs.

Main Results:

• Low variation was observed in functional regions of microRNAs themselves.
• An appreciable level of variation was found at miRNA target sites, with approximately 400 SNPs at conserved or verified sites.
• Around 250 SNPs were identified that could create novel miRNA target sites in the human genome.
• Some SNPs at target sites showed high population frequencies and evidence of positive selection.

Conclusions:

• Human genomes harbor significant variation at microRNA target sites, distinct from variation within miRNA genes.
• These variations, particularly SNPs, have the potential to influence gene expression and human phenotypes.
• Certain variations at miRNA target sites may be under selection, indicating functional relevance.