Functional Implications of Human-Specific Changes in Great Ape microRNAs

Area of Science:

• Genomics
• Evolutionary Biology
• Molecular Biology

Background:

• MicroRNAs (miRNAs) are key post-transcriptional gene regulators essential for biological processes.
• While miRNAs are conserved across species, lineage-specific changes and their role in human-ape divergence remain understudied.

Purpose of the Study:

• To investigate the evolutionary history and functional impact of human microRNAs in great apes.
• To identify species-specific nucleotide substitutions in microRNAs and assess their biological relevance in human evolution.

Main Methods:

• Analysis of high-coverage genomes from 82 individuals (gorillas, orangutans, bonobos, chimpanzees, humans).
• Assessment of purifying selection across microRNA regions (seed, mature, precursor).
• Cataloging species-specific nucleotide substitutions and functional analysis of selected miRNAs (miR-299-3p, miR-503-3p, miR-508-3p, miR-541-3p).

Main Results:

• Seed and mature microRNA regions exhibit stronger purifying selection than precursor regions.
• A comprehensive catalog of species-specific nucleotide substitutions in microRNAs among great apes was created.
• Lineage-specific substitutions and length changes in four miRNAs alter gene expression, target repertoires, and regulatory networks.

Conclusions:

• Studied molecular changes in microRNAs could have modified critical functions, shaping human-specific phenotypes.
• This research provides a framework for studying the evolutionary impact of regulatory changes in human lineage.