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Where am I in the cell?

Part of the cell · Necessary gene regulation

Switching genes on and off

On the cell picture: Signal transduction

The small amount of regulation the cell cannot do without — starting its housekeeping genes and keeping iron from running loose.

Proteins in the model: 79

Part of the model's 1051 proteins. Each group below is a book group, counted in the working count after the repeats and non-first-cell groups were removed. The proteins are not yet matched gene by gene.

GroupProteins
Protein dephosphorylation code4
Post-translational modification code3
PhoR-PhoB signaling system3
Quorum sensing system2
LuxPQ-LuxU-LuxO system3
Signaling metabolites3
ATP/ADP Energy Balance Code5
Redox Code pathway5
Energy sensing and adaptation4
Nutrient sensing and adaptation44
Gene regulators3

Its pathways

  1. Transcription controlatlas pathway2
  2. Not yet placed in a pathwayto sort2

If it fails

The basic gene programme never starts, or free iron drives damaging chemistry unchecked.

Dies at once · within the current generation

What it depends on

What it supplies

None listed in the curated set.

Dependencies are curated from the book at the level of the map’s systems and are not measured protein contacts. See all systems together.

How it is built and controlled

Counts from UniProt annotations of this group’s proteins.

Its place in the control layer

Signaling pathways

Gene regulatory network

From the control-layer pages. Which genes a regulator controls is mostly inferred from related bacteria, because Aquifex has no genetic system for testing it directly.

Origins

What needs to be explained

How did a detectable change become linked to a useful response and an inheritable regulatory architecture?

What needs explaining. Explain how sensing and response became linked to a useful physiological outcome rather than merely to chemical reactivity.

Hurdles

  1. H-REG-1Signal–response couplingThe problem. Responding to a change means linking a sensor (for example a histidine kinase) to a regulator and to the genes it controls.Why it is hard. Each link is a specific molecular interaction; the sensor, the regulator and the DNA binding site must all match.Information and controlStage 2: One step shown on its ownShown: Laboratory-selected RNAs can change their activity when they bind a small molecule.In the books: 270 open problems on codes, signaling, regulation and adaptation ↗
  2. H-REG-2SpecificityThe problem. Each sensor must respond to its own signal and talk only to its own partner, although many similar systems exist side by side.Why it is hard. Cross-talk between similar sensors and regulators would trigger the wrong responses.Information and controlStage 0: Not yet addressed by experimentShown: not yet addressed by experiment.In the books: 270 open problems on codes, signaling, regulation and adaptation ↗
  3. H-REG-3TimingThe problem. Responses must be fast enough to follow environmental change and stable enough not to switch back and forth.Why it is hard. Achieving both needs feedback and finely set binding strengths.Information and controlStage 0: Not yet addressed by experimentShown: not yet addressed by experiment.In the books: 270 open problems on codes, signaling, regulation and adaptation ↗
  4. H-REG-4CostThe problem. Regulators are proteins that must be made and maintained even while the condition they respond to is absent.Why it is hard. Their material and energy costs come out of the same budget as growth.The integrated cellStage 0: Not yet addressed by experimentShown: not yet addressed by experiment.In the books: 270 open problems on codes, signaling, regulation and adaptation ↗
  5. H-REG-5Encoded responsesThe problem. The link between signal and response must be written in genes (regulator sequences and binding sites) so every daughter cell responds the same way.Why it is hard. Regulation is information: it has to be stored, copied and read like the rest of the genome.Information and controlStage 0: Not yet addressed by experimentShown: not yet addressed by experiment.In the books: 270 open problems on codes, signaling, regulation and adaptation ↗
Naturalistic proposal

Scope. Present regulatory interdependence does not establish that every named modern signaling pathway existed in the first cells. Each proposed precursor network needs its own mechanism and evidence.

Experimental progress. Genetic and structural analyses connect phosphate transport-associated proteins with PhoR–PhoB signaling in Escherichia coli. This investigates a particular regulatory mechanism, rather than every bacterial phosphate response.

What would strengthen a natural account. Steps shown to work together under plausible early-Earth conditions, without a chemist choosing the reagents, purifying the products or changing conditions between steps, would strengthen a natural account of origins in proportion to what they explain. Loss of a claimed dependency or discovery of functional alternatives would weaken the corresponding design argument. Gaps in the record do not supply a numerical likelihood for either explanation.

Design analysis

Observations. Production can change with physiological demand. Regulatory feedback links activity to later activity through identifiable signals.

Hallmarks that apply.

The author’s conclusion. The coordinated features give the author a positive reason to consider design within the wider cellular architecture. For this local system alone, they do not establish that design is uniquely the best historical explanation. The conservative inference is that the system contributes to a cumulative design case, with its weight conditional on the comparative evidence and on how much plausible natural pathways explain.

From the book article Codes, Signaling, Regulation and Adaptation Systems, with its scientific references.

How it was discovered

  1. 1961Jacob and Monod propose the operon: genes switched on and off together by a repressor (Nobel Prize 1965).Jacob & Monod, Journal of Molecular Biology 3:318–356 (1961)
  2. 1966Gilbert and Müller-Hill isolate the lac repressor, the first gene-regulating protein to be purified.Gilbert & Müller-Hill, PNAS 56:1891–1898 (1966)
  3. 1969Cashel and Gallant find the “magic spot” (p)ppGpp, the alarm signal of starving bacteria.Cashel & Gallant, Nature 221:838–841 (1969)
  4. 1986Two-component systems, in which a sensor protein passes a signal to a response protein, are recognised as a family.Nixon, Ronson & Ausubel, PNAS 83:7850–7854 (1986)
  5. 2002Riboswitches are discovered: messenger RNAs that switch genes on or off by binding a small molecule directly.Winkler, Nahvi & Breaker, Nature 419:952–956 (2002)

Each hurdle above is sorted by kind and by how far experiments have got (see “How hurdles are sorted” at the top).

All parts of the cell side by side: origins hub. The book articles:

Sources