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Explore the intricate connections within gene networks, uncovering the adaptability and redundancy that enable diverse phenotypic outcomes. Dive into the interplay of molecular components influencing cellular functions and behaviors, shedding light on the subtle yet impactful alterations that shape biological systems. Investigate the parallel pathways and cross-talk mechanisms that govern genetic responses to environmental cues, revealing the remarkable plasticity of gene networks in orchestrating physiological processes. Join the exploration of gene network dynamics, from regulatory elements to emergent properties, unveiling the intricate balance between stability and flexibility in shaping complex biological systems.
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Degeneracy and Flexibility in Gene Networks Ralph J. Greenspan The Neurosciences Institute San Diego, CA
mRNAs Higher in hi5 (199/8449) Gene expression swallow RNA binding protein Signal transduction nemo serine/threonine protein kinase Cytoskeleton & protein localization Pendulin nuclear importin a2-subunit zipper cytoplasmic myosin II heavy chain Klp67A kinesin-like protein Chaperones Hsp90 Hsp27 Hsp70 Hsp22 Hsp60
mRNAs Higher in lo (52/8449) Gene expression prospero homeodomain protein Circadian rhythms Pigment-dispersing factor neuropeptide cryptochrome photoreceptor protein Axon guidance abLIM actin-binding protein Immune system Attacin-A immune defense protein croquemort macrophage receptor
Importin-a (Pendulin) Pigment dispersing Factor (Pdf) cryptochrome (cry)
A’’ A’ A B’’ B’ B N’ N’’ N Genes Cells Phenotype
temperature-sensitive syntaxin (Syx1A) mutant % standing time 25oC 38oC
Isolation of syx suppressors syx + % standing syxSup + + time at 38oC van Swinderen and Greenspan (2005)
syx Suppressors Gene expression ETS domain zinc finger C2H2 NLS motif Srp54 (splicing factor) ATP-dependent DNA helicase S12 (ribosomal protein) Cytoskeleton troponin-C superfamily Actin 42A Chaperone kismet Metabolism pyruvate dehydrog. kinase Gdp-mannose \dehydratase Miscellaneous Cecropin-like A bunch of genes that don’t make sense 5 others unknown van Swinderen and Greenspan (2005)
observed expected Sup1Sup2 + + Sup1Sup2 + + Interaction between syx suppressors % standing time at 38oC van Swinderen and Greenspan (2005)
observed expected Sup1Sup2 + + Sup1Sup2 + + and in the presence of the syx- mutation syx + % standing syx + time at 38oC van Swinderen and Greenspan (2005)
syx + matrix 1 positive interaction negative interaction van Swinderen and Greenspan (2005)
syx- matrix 1 previous interaction missing interaction reversed sign van Swinderen and Greenspan (2005)
syx- matrix 1 previous interaction missing interaction reversed sign new interaction van Swinderen and Greenspan (2005)
syx+ matrix 2 positive interaction negative interaction
syx-matrix 2 previous interaction missing interaction reversed sign
syx-matrix 2 previous interaction missing interaction reversed sign new interaction
Gene networks appear to be responsive to changes (even mild changes) anywhere in the system.
Can you affect any phenotype from anywhere in the genome?
“Matrix” Experiment • 8 loci • range of functions and phenotypes • all expressed in the nervous system • place on common genetic background • test all pairwise combinations for 8 • different behaviors
Pendulin importin-a
Cysteine-string-protein synaptic transmission
Itp-r83A inositol-1,4,5-triphosphate receptor
methuselah G-coupled receptor
TBP-related factor TATA-box binding protein
nalyot/Adf1 Adf1 Adf1 Pol II transcription factor
Nemo Nemo Serine/threonine kinase
cnk Ras pathway modifier
Falling over % fainted time 25oC 38oC
Large phenotypic effect nal Csp mth Trf Itp Pen cnk Nemo Cl Cd Cd Cd G τ F F F F F nal G G Csp F Cl τ Cl Cd mth τ G F F Trf F Itp Cl F Pen F Nemo cnk