Molecular clock

Molecular clock detects and quantifies violations of the molecular clock hypothesis in protein sequence and structural evolution to assess rate heterogeneity across protein superfamilies.

Key Features:

• Statistical Testing: Implements a novel statistical test named Significant Clock Violations (SCV) to evaluate deviations from constant substitution rates.
• Dual Analysis Capability: Assesses clock violations in both protein sequences and protein structures for comparative evaluation of evolutionary dynamics.
• Large-scale Assessment: Performs analyses across three extensive protein superfamilies to provide broad and generalizable results.
• Validation through Simulations: Validates the method using computer simulations prior to application to empirical data.

Scientific Applications:

• Comparative Evolutionary Analysis: Examines differences between sequence and structural evolution to infer how evolutionary pressures act at distinct molecular levels.
• Functional Change Correlation: Identifies associations between functional annotations (Gene Ontology and InterPro terms) and significant clock violations in structure evolution.
• Detection of Positive Selection: Highlights cases where accelerated evolution is more evident in structural data than in sequence data, indicating potential positive selection.

Methodology:

Applies the Significant Clock Violations (SCV) statistical test to compare evolutionary rates between protein sequences and structures across three superfamilies and validates findings using computer simulations.