SSS-test: a novel test for detecting positive selection on RNA secondary structure

Area of Science:

• Genomics
• Evolutionary Biology
• Bioinformatics

Background:

• Long non-coding RNAs (lncRNAs) regulate gene expression and phenotypes.
• RNA structure is crucial for function, yet selection studies often focus on sequence.
• Existing methods primarily detect negative selection on RNA structure, necessitating new approaches for positive selection.

Purpose of the Study:

• To develop a computational method for detecting positive selection on RNA secondary structures.
• To identify long non-coding RNAs (lncRNAs) under positive selection in the human lineage.
• To investigate adaptive evolution in lncRNAs associated with cognitive and psychiatric disorders.

Main Methods:

• Introduction of the SSS-test (Selection on Secondary Structure test).
• Benchmarking the SSS-test using biological and synthetic controls.
• Application of the SSS-test to a large collection of human lncRNA families.

Main Results:

• The SSS-test successfully identifies both positive and negative selection on RNA structures.
• 110 out of 15,443 lncRNA families showed evidence of positive selection in humans.
• Local structures in 26 lncRNAs linked to psychiatric disorders exhibited signs of positive selection in the human lineage.

Conclusions:

• Genome-wide assessment of positive selection on RNA secondary structures is feasible.
• Human-specific positive selection in lncRNAs associated with cognitive disorders offers candidates for further research.
• Findings may illuminate the evolutionary basis of human cognitive abilities.