Evolutionary dynamics of microRNA target sites across vertebrate evolution

Area of Science:

• Genetics
• Evolutionary Biology
• Molecular Biology

Background:

• MicroRNAs (miRNAs) are key regulators of gene expression, primarily targeting messenger RNA (mRNA) 3' untranslated regions (3'UTRs).
• The evolutionary dynamics and selective pressures governing the gain and loss of miRNA target sites remain poorly understood.
• Understanding these pressures is crucial for deciphering gene regulation and evolution.

Purpose of the Study:

• To quantify the selective pressures acting on miRNA target sites within 3'UTRs.
• To investigate the evolutionary patterns of target site gain and loss for ancient animal miRNAs.
• To characterize variations in selective constraint across different miRNAs and transcripts.

Main Methods:

• Developed a quantitative approach to assess selective pressures on miRNA target sites.
• Analyzed evolutionary rates of target site gain and loss across mammalian evolution.
• Examined selection against mutations affecting target site efficacy.

Main Results:

• Selective pressure extends to recently substituted miRNA target sites, not just deeply conserved ones.
• Ancient miRNAs exhibit distinct evolutionary patterns, categorized into three groups based on target site gain/loss rates.
• Mutations altering target site strength are generally disfavored, with varying selection intensity across miRNAs and transcripts.

Conclusions:

• MiRNA target site evolution is shaped by diverse selective pressures, differing significantly even among ancient miRNAs.
• Some miRNAs like miR-20 and miR-30 show broad, conserved targeting, while others like mir-146 display rapid target site evolution.
• The developed approach provides valuable insights into miRNA-target coevolution and can be applied to other regulatory motifs.