PHACE: Phylogeny-Aware Detection of Molecular Coevolution.

ABSTRACT: The coevolution trends of amino acids within or between genes offer key insights into protein structure and function. Existing tools for uncovering coevolutionary signals primarily rely on multiple sequence alignments, often overlooking phylogenetic relatedness and shared evolutionary history. Here, we introduce PHACE, a phylogeny-aware coevolution algorithm that maps amino acid substitutions onto a phylogenetic tree to detect molecular coevolution. PHACE categorizes amino acids at each position into "tolerable" and "intolerable" groups, based on their independent recurrence across the tree, reflecting a position's tolerance to specific substitutions. Gaps are treated as a third character type, with only phylogenetically independent gap changes considered. The method computes substitution

SUBMITTER: Kuru N 

PROVIDER: S-EPMC12264334 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature