Evolution of the orthopoxvirus core genome

Area of Science:

• Virology
• Evolutionary Biology
• Genomics

Background:

• Orthopoxviruses are significant pathogens, with genome evolution studies focusing on gene gains/losses.
• Core genes, conserved across orthopoxviruses, offer a unique perspective on evolutionary constraints.

Purpose of the Study:

• To investigate evolutionary pressures on conserved orthopoxvirus genes, particularly focusing on positive selection.
• To identify specific genes and regions under selection, including those related to immune response and viral replication.
• To explore the role of intrinsically disordered regions (IDRs) in poxvirus evolution.

Main Methods:

• Comparative genomic analysis of orthopoxvirus core genes.
• Phylogenetic analysis to detect positive selection events.
• Identification and analysis of intrinsically disordered regions (IDRs) in poxvirus proteomes.

Main Results:

• Positive selection was detected in genes involved in viral morphogenesis and transcription/replication, despite strong evolutionary constraints.
• Immunomodulatory genes showed less pervasive positive selection, though some, like E3L, A24R, and H3L, may have evolved under immune pressure.
• Episodic positive selection was prevalent in internal phylogenetic branches and the monkeypox virus lineage, notably affecting the D14L gene.
• Genes B1R and A33R, involved in intra-genomic conflict, were targeted by episodic selection multiple times.
• Intrinsically disordered regions (IDRs) in orthopoxvirus proteomes are less constrained and frequently targeted by positive selection.
• Poxvirus IDR fraction is modulated by GC content, suggesting a mechanism for maintaining disorder.

Conclusions:

• Core gene analysis reveals significant positive selection shaping orthopoxvirus evolution, particularly in viral replication and morphogenesis.
• Specific genes and IDRs are identified as key drivers of phenotypic variation in orthopoxviruses.
• The findings offer insights into the adaptive evolution of poxviruses and potential targets for antiviral strategies.