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Robustness and genetic networks

Robustness and genetic networks. Eörs Szathmáry. Collegium Budapest Eötvös University. Selected members of five gene classes. Only one segment polarity gene is shown Most of the proteins are transcriptional activators. Some regulatory interactions that esablishing gap gene expression.

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Robustness and genetic networks

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  1. Robustness and genetic networks Eörs Szathmáry Collegium Budapest Eötvös University

  2. Selected members of five gene classes • Only one segment polarity gene is shown • Most of the proteins are transcriptional activators

  3. Some regulatory interactions that esablishing gap gene expression • Krüppel is expressed in the grey region • Bicoid is an activator • Hunchback and giant are repressors • Inelegant mechanism!

  4. Cooperativity in biomolecule activity • The degree of cooperativity can be measured by the Hill coefficient: the slope at inflection point • Common in transcriptional regulation and ligand-receptor interactions

  5. Expression of segment-polarity genes in the embryo • Pair rule gene expression patterns regulate engrailed and wingless expression • 14 parasegments are thus formed at en/wg boundaries • True segment boundaries are displaced one cell to the right of the parasegment boundaries

  6. A model for the maintenance of segment polarity gene expression • Gene expression patterns (black in a) • Part of the segment polarity network (lowercase: genes, uppercase: gene products) • Each cell has one such network

  7. Space of functional segment polarity networks • 22 parameters out of 48 are shown • Gray polygons yield functional networks • Kxy: concentration of X at which activity of y is half maximal, etc.. • Mean and standard variation for polygons are shown

  8. Some insights • Extremely robust to variation in individual parameters • Also against change in netwok topology • Robust against change in concentration also

  9. Let us borrow a model from neural networks Only two states: on and off Activators and inhibitors influence the weight Switch-like cooperativity 60% of random changes gives the same expression pattern One can select for networks with even higher robustness A theoretical treatment

  10. Dorsal view of the Drosophila wing • Heat-shock treatment induces the disappearance of cross-veins • One can select for or against this sensitivity • Genetic assimilation: some show the phenotype without the inducer! • Does not work with inbred lines

  11. Incidence of Hsp90-induced eye deformities • Hsp90 associates with signal-transduction molecules • Lines can be selected for tolerance of mutation of Hsp90

  12. Many ways of building the same body: the sea urchin

  13. Larvae can be very different • Feeding pluteus (a) • A non-feeding larva (b) • Direct development (c)

  14. Evolution of developmental modes • Black bars: direct development • Most adult forms are conserved • Ecological correlates: direct development  no dispersal, large eggs

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