1. The Structure and Plasticity of the Phenotype as a Network Phenomenon George Kampis Basler Chair Spring 2007, ETSU, Johnson City, TN

5. Gene environment interaction Variability of expression (G) Plasticity of development (G x E) Variability of phenotype (E) Complete model (as large as the world) Here one segment, the organism

6. Phenotype based evolution

7. Historical/Autobiographical Waddington, C.H., ed. 1972. Towards a Theoretical Biology, vols. 1-4. Edinburgh: Edinburgh University Press. 1970s-1980s: Biological Systems Theory S. Kauffman, R. Rosen, H. Pattee, B. Goodwin, S. Oyama, F.J. Varela… Ridicule, e.g. „deconstructivists of the gene” (Dennett 1995: DDI)

8. Kampis, G. 1991: Self-Modifying Systems: A New Framework for Dynamics, Information, and Complexity, Pergamon, Oxford-New York, pp 543+xix.

9. A down-to-Earth picture Genes 1970-1980: 10-100 million genes 1985: 1 million genes Human Genome Project: 100,000 genes 2001: 30,000 genes 2003: 20,000 genes –Out of which Drosophila alone has 5,000 Gene products (PIM) 1980-85: 1,000- x,000 E.Coli 2003: 20,000 Drosophila 2007: 35,000 (?) yeast

10. More on down-to-Earth time complexity Relevant complexity Brute force

11. One sentence metaphors… StructureGenes Structure and functionGenes „plus” FunctionNetwork Complexity of representation regulation, pleiotropy, epistasis, etc.. Numbers shrinking (increasing): proportions change Transparency disappears

12. Summary so far We are not smarter, we just know more.

13. Some examples for networks Drosophila PIM (2003) Yeast PIM (2006)

16. Causality and explanation Event view –If A then B (… if not A not B…) etc Contributing causes –If A (and B and C) then B Multiple causation –If A (or B or C) then B Network causation –If (network ) then B

17. Network causation Not event like (c.f. gravitation, symmetry) Not individuated Handles (on trait development): –„Classical” (vary nodes: percolation of effects) –„Nonclassical”: network transformations

18. The organism as a network 10 9 15 24 3 23 4 55 64 23 12 54 67 89 25 39 19 51 43 432 (dyamic) phenotpye vector, PIM and developmental network (map) behind Representation problem (mixed nodes, mixed edges) Proteins, properties, … e.g. blue eye

19. A unified framework for.. Gene expression Development Adaptation Learning and environmental induction Phenotype plasticity …

20. Genes: your outside is in Genes are „hidden” inside net topology For phenotype to phenotype interactions Most nodes are distant, „nontransparent” The whole network is the target of selection How does it permit/evoke different subnetworks w/ different properties interactor replicator

21. Network transformations Growing network: stability, connectivity Strong links vs weak links Edge removal/addition w. phase transition (e.g. star/SF)

22. Random vs real networks

23. Connectivity/stability in ecosystems Translates as a diversity/stability problem in ecology May-Wigner theorem (1971): low connectivity stabilizes McCann (2000): high diversity/generalist species stabilize In cells: e.g. the role of chaperons Hubs (not the genes ?!) Topological „side” effects

24. NaNu in a new skin Old question: how much responsibility is exported from G to E (e.g. default envir.) New question: how much of the environment effects is internally controlled Network props not modifiable are few and far between

25. Summary Not, G, E, or GxE But rather x, where x = network topology A dominant and independent causal factor

26. Not considered in this talk Modularity (e.g. HOX genes, segments) Self organization (e.g. spatial perturbation) Hierarchical levels (Cells, Organs, etc.) Modes of inheritance and their roles … and many other issues

27. Thank you!