CisRegTest

CisRegTest detects and quantifies natural selection acting on transcription factor binding sites (TFBS) within regulatory genomic regions by analyzing nucleotide substitutions to infer selection pressures.

Key Features:

• Focus on Transcription Factor Binding Sites: Targets TFBS to evaluate how nucleotide substitutions affect binding strength and regulatory function.
• Statistical Testing Framework: Employs statistical tests that compare observed substitutions altering TFBS strength against neutral expectations.
• Types of Selection: Distinguishes purifying selection, which conserves binding site strength, from positive selection, which can create, destroy, or alter TFBS affinities.
• Model-Based Approach: Uses standard models of binding site strength and molecular evolution to infer selection in the absence of direct experimental data.

Scientific Applications:

• Evolutionary Biology: Infers evolutionary mechanisms shaping gene regulation by detecting selection on regulatory elements such as TFBS.
• Comparative Genomics: Identifies conserved and divergent regulatory elements between species by detecting TFBS under selection pressures.
• Functional Genomics: Links selective forces on TFBS to effects on gene expression and phenotypic diversity.
• Empirical Validation: Application to well-characterized regulatory regions in Drosophila has demonstrated detection of purifying selection.

Methodology:

Applies statistical models to observed nucleotide substitution patterns in TFBS, using models of binding site strength and molecular evolution to infer purifying or positive selection.