Date of Award
2009
Degree Type
Thesis
Degree Name
Master of Science
Program
Applied Mathematics
Supervisor
Dr. Lindi WahlMutual information (MI) is a measure frequently used to find co-evolving sites in protein families. However, factors unrelated to protein structure and function, in particular sampling variance in amino acid counts and complex evolutionary relationships among sequences, contribute to ML Understanding the contribution of these components is essential for isolating the MI associated with structural or functional co-evolution. To date, the contributions of these factors to mutual information have not been fully elucidated. We find that stochastic variations in amino acid counts and shared phylogeny each contribute substantially to measured MI. Nonetheless, the mutual information observed in real-world protein families is consistently higher than the expected contribution of these two factors. In contrast, when using synthetic data with realistic substitution rates and phylogenies, but without structural or functional constraints, the observed levels of MI match those expected due to stochastic and phylogenetic background. Our results suggest that either low levels of co-evolution are ubiquitous across positions in protein families, or some unknown factor exists beyond the currently hypothesized components of intra-protein mutual information: sampling variance, phylogenetics and structural/functional co-evolution.
Abstract
Mutual information (MI) is a measure frequently used to find co-evolving sites in protein families. However, factors unrelated to protein structure and function, in particular sampling variance in amino acid counts and complex evolutionary relationships among sequences, contribute to ML Understanding the contribution of these components is essential for isolating the MI associated with structural or functional co-evolution. To date, the contributions of these factors to mutual information have not been fully elucidated.
We find that stochastic variations in amino acid counts and shared phylogeny each contribute substantially to measured MI. Nonetheless, the mutual information observed in real-world protein families is consistently higher than the expected contribution of these two factors. In contrast, when using synthetic data with realistic substitution rates and phylogenies, but without structural or functional constraints, the observed levels of MI match those expected due to stochastic and phylogenetic background.
Our results suggest that either low levels of co-evolution are ubiquitous across positions in protein families, or some unknown factor exists beyond the currently hypothesized components of intra-protein mutual information: sampling variance, phylogenetics and structural/functional co-evolution.
Recommended Citation
DeHaan, Christopher S., "Finite sample sizes and phylogeny do not ACCOUNT FOR THE MUTUAL INFORMATION OBSERVED FOR MOST SITE-PAIRS IN MULTIPLE SEQUENCE ALIGNMENT" (2009). Digitized Theses. 4090.
https://ir.lib.uwo.ca/digitizedtheses/4090