Evolution of the hepatitis E virus polyproline region: order from disorder

Area of Science:

• Virology
• Molecular Biology
• Genetics

Background:

• The hepatitis E virus (HEV) polyproline region (PPR) is an intrinsically unstructured region (IDR).
• IDRs are crucial for regulating transcription and translation by binding multiple ligands.
• Previous assumptions attributed HEV PPR variability to high insertion/deletion rates.

Purpose of the Study:

• To investigate the mutation rate and evolutionary pressures on the HEV PPR.
• To understand the mechanisms behind nucleotide variability in the HEV PPR.
• To correlate amino acid usage patterns with IDR formation in HEV.

Main Methods:

• Comparative analysis of HEV PPR sequences across all genotypes.
• Mutation rate analysis of the PPR compared to the nonstructural polyprotein.
• Codon usage analysis to identify shifts in nucleotide occupation.

Main Results:

• The mutation rate in the HEV PPR is similar to other nonstructural regions.
• The PPR exhibits higher tolerance for substitutions at the first and second codon positions.
• This leads to increased cytosine usage, favoring proline, alanine, serine, and threonine over aromatic amino acids.

Conclusions:

• HEV PPR evolution is driven by selection for increased proline content and IDR formation.
• The carboxyl half of the PPR is more mutation-tolerant than the amino half.
• This adaptability favors the formation of functional IDR structures crucial for HEV.