Interplay between RNA structure and protein evolution in HIV-1

Area of Science:

• Virology
• Molecular Biology
• Evolutionary Biology

Background:

• RNA viruses possess extensive secondary structures crucial for noncoding and synonymous site evolution.
• The impact of RNA secondary structures on protein evolution remains less understood.
• Recent experimental determination of the HIV-1 RNA genome's secondary structure provides a basis for investigation.

Purpose of the Study:

• To investigate the interdependence of RNA structure and protein evolution in HIV-1.
• To explore the correlation between genomic RNA base pairing and amino acid variability.
• To understand the implications of RNA-protein evolutionary trade-offs for HIV-1 variability and drug resistance.

Main Methods:

• Analysis of experimentally determined HIV-1 RNA genome secondary structure.
• Correlation analysis between the extent of base pairing in genomic RNA and amino acid variability.
• Assessment of the fitness costs associated with RNA base pair disruption for drug resistance mutations.

Main Results:

• A significant negative correlation was observed between genomic RNA base pairing and amino acid variability.
• Relaxed RNA structures appear to facilitate protein genetic variation accumulation.
• Protein-level sequence changes can disrupt existing RNA structures.
• Disruption of RNA base pairs may impose fitness costs on drug resistance mutations in protease and reverse transcriptase.

Conclusions:

• RNA structure and protein evolution are not independent processes in HIV-1.
• Evolutionary trade-offs exist between selective pressures at the RNA and protein levels.
• Understanding these trade-offs is key to comprehending HIV-1 variability and evolution, including the spread of drug resistance.