Variation of Regulatory Networks Across Organisms

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Comparative analysis of 12 Drosophila genomes (50 My divergence) inspects 121 ortholog C2H2 zinc fingers using structural positions and Marcus’s bacterial one‑hybrid dataset (~160,000 interfaces) to predict DNA specificity; about a third of domains show changes in the four specificity residues and ~70% of D. melanogaster C2H2 genes carry variable domains, with predicted specificity shifts increasing with phylogenetic distance. Separate structural mapping of cancer somatic missense mutations shows enrichment at interaction sites while human polymorphisms are depleted; ~22% of proteins have PDB-mapped interfaces, extendable to ~60% with domain-based models.

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1. 0:00Start
2. 4:47DISEASE CASE STUDIES: TRANSCRIPTION FACTOR VARIATION
3. 13:33DROSOPHILA FRUIT FLY PHYLOGENETIC TREE
4. 18:56LOWER EVOLUTIONARY RATES FOR DIVERGED BINDING RESIDUES
5. 24:42CONTRIBUTES TO REGULATORY NETWORK EVOLUTION
6. 33:08NETWORK VARIATION IN HEALTHY AND DISEASE INDIVIDUALS