Ancestor

Ancestor reconstructs ancestral amino acid sequences from homologous amino acid sequences given a phylogenetic tree to identify amino acid substitutions underlying protein evolution.

Key Features:

• Inference Methods: Implements maximum-parsimony (MP), maximum-likelihood (ML), and a distance-based method for ancestral sequence inference.
• Accuracy Across Divergence Levels: All three methods provide reliable inference at low sequence divergence, while ML and the distance method outperform MP as sequence divergence increases, particularly on trees with long branches.
• Robustness to Sequence Changes: Adding or removing a few present-day sequences does not substantially alter inferred ancestral amino acids.
• Model Sensitivity: Accuracy of ML and the distance method is sensitive to the substitution model; an incorrect model reduces accuracy, though these methods still tend to outperform MP under model misspecification.
• Tree Topology Tolerance: Maintains high accuracy in correctly resolved portions of the phylogenetic tree even when the overall tree topology is partially incorrect.

Scientific Applications:

• Evolutionary Studies: Reconstructs ancestral sequences to trace evolutionary changes and identify substitutions that influenced protein function.
• Functional Analysis: Identifies critical amino acid substitutions for studying functional evolution of proteins.
• Model Testing: Enables testing of amino acid substitution models to evaluate their effects on ancestral inference accuracy.

Methodology:

Uses maximum-parsimony by minimizing the number of changes, maximum-likelihood by estimating the probability of the observed data given a model of evolution, and a distance method that computes evolutionary distances between sequences to infer ancestral states.