protTrace

protTrace estimates the evolutionary traceability of proteins to quantify when sequence-similarity decay limits ortholog detection and to inform inference of ancient gene sets and functional conservation.

Key Features:

• Evolutionary Traceability Measure: Introduces a metric called "evolutionary traceability" that quantifies the evolutionary distance beyond which ortholog search sensitivity becomes limiting.
• Application to Yeast Genes: Applied to yeast genes, showing that high-traceability genes are often involved in catalysis, ion transport, and ribonucleoprotein complex assembly, functions inferred to date back to LUCA.
• Insights into Gene Functions: Identifies that genes with insufficient traceability for inferring presence at LUCA are enriched for regulatory functions.
• Essential Genes Analysis: Analyzes genes essential for self-replicating cells and identifies many bacterial-restricted genes with low traceability, raising questions about overlooked orthologs in eukaryotic and archaeal domains.
• Case Study — REC8 Protein: Demonstrates that adjusting search sensitivity based on traceability can uncover previously missed orthologs of REC8 in rapidly evolving organisms such as microsporidia.

Scientific Applications:

• Gene Set Reconstruction: Aids refinement of gene set reconstructions across different domains of life by accounting for detection limits due to sequence-similarity decay.
• Functional Network Conservation: Improves distinction between true ortholog absence and detection failure, informing analyses of protein network conservation and evolution.
• Evolutionary Biology Research: Enables analysis of evolutionary relationships, gene function, adaptation, and traceability across diverse species.

Methodology:

Employs a simulation-based framework that analyzes orthologs and their decay in sequence similarity over time to compute evolutionary traceability and quantify the point at which ortholog searches become unreliable.