Special Chemical Engineering Seminar

Standard bioinformatics pipelines for comparative genomic data analysis typically include steps like multiple sequence alignment, phylogenetic tree reconstruction, calculation of the ratio of rates of nonsynonymous to synonymous nucleotide substitution (dN/dS), and gene tree-species tree reconciliation. Models for amino acid substitution used in these processes assume that each site evolves independently according to average properties in the absence of a protein structural or functional context. Models for duplicate gene retention assume that the process is evolutionarily neutral and do not consider functional or mechanistic underpinnings. A model for duplicate gene retention that would allow for mechanistic differentiation between nonfunctionalization, neofunctionalization, subfunctionalization, and dosage balance based upon differences in expected time-dependent retention profiles is presented. Two characterizations of amino acid substitution are also presented. One approach extends a population genetic model to inter-specific genomic data and a second approach evaluates the effects of selection for protein folding and protein-protein interaction on sequence evolution. These approaches reflect an in progress strategy for increasing biochemical and evolutionary realism in bioinformatics.