HexSE

HexSE simulates nucleotide sequence evolution along phylogenetic trees while modeling overlapping reading frames (OvRFs) to account for multiple selection pressures and their effects on synonymous and non-synonymous substitution rates (dN/dS).

Key Features:

• Overlapping reading frames (OvRFs): Simulates evolution in genomes where nucleotides encode multiple genes in different reading frames.
• Phylogenetic simulation: Simulates nucleotide sequence evolution along phylogenetic trees.
• Frame-specific selection (dN/dS): Models distributions of selection biases (dN/dS) across different reading frames to represent multiple selective constraints.
• Parameterized substitution rates: Incorporates stationary nucleotide frequencies and transition biases into substitution rate calculations.
• Per-site tracking: Uses a custom data structure to track substitution rates at each nucleotide site under overlapping constraints.
• Genome architecture support: Handles arbitrary distributions of open reading frames within linear and circular genomes.
• Implementation: Implemented as a Python module.

Scientific Applications:

• Viral genome evolution: Modeling evolutionary dynamics in viral genomes where overlapping genes are common.
• Interpretation of dN/dS: Evaluating how overlapping reading frames affect interpretation of synonymous and non-synonymous substitution rates (dN/dS).
• Molecular evolution in compact genomes: Assessing constraints and adaptive strategies in organisms with compact, overlapping genomic architectures.

Methodology:

Simulates sequence evolution along a phylogeny using a model that assigns per-site substitution rates via a custom data structure influenced by stationary nucleotide frequencies, transition biases, and frame-specific dN/dS distributions, and that supports arbitrary ORF arrangements in linear and circular genomes. Implemented in Python.