Part of the cell · Nucleotide biosynthesis and recycling
Making DNA and RNA letters
On the cell picture: Nucleotide biosynthesis
The four letters of DNA and RNA are built here from simpler pieces. None are supplied in the medium and there is nothing to recycle.
Proteins in the model: 51
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.
| Group | Proteins |
|---|---|
| De novo purine biosynthesis | 11 |
| Purine biosynthesis - adenine pathway | 4 |
| Purine biosynthesis - guanine pathway | 5 |
| De novo pyrimidine biosynthesis | 9 |
| Uracil biosynthesis | 6 |
| Cytosine nucleotide biosynthesis | 3 |
| Thymine biosynthesis | 4 |
| Nucleotide phosphorylation | 2 |
| Nucleotide Salvage | 4 |
| RNA processing and degradation | 3 |
Its pathways
- Purine biosynthesisatlas pathway10
- Pyrimidine biosynthesisatlas pathway9
- Interconversion and salvageatlas pathway8
- Deoxyribonucleotide supplyatlas pathway3
- Aromatic amino acidsatlas pathway2
- Purine metabolismKEGG map5
- Pyrimidine metabolismKEGG map4
- Histidine metabolismKEGG map2
- Not yet placed in a pathwayto sort4
If it fails
The pool of nucleotides runs down, and both copying DNA and reading genes stop.
Starves of a building block · 1–2 generations
What it depends on
- Building carbon into moleculesCarbon precursors supply the ribose and ring-building substrates needed for nucleotide synthesis.Book pp. 499–500
- Making the twenty amino acidsAmino acids donate nitrogen and other atoms to purine and pyrimidine biosynthesis.Book pp. 499–500
- Manufacturing cofactors and vitaminsSelected nucleotide reactions require one-carbon or redox cofactors.Book pp. 498–500
- Turning hydrogen into usable energyEnergy investment supports nucleotide synthesis and phosphorylation.Book pp. 499–500
What it supplies
- Copying and repairing the genomeDeoxyribonucleotides are the monomers used to replicate and repair DNA.Book pp. 499–501
- Reading genes into RNA, Building proteins and folding themRibonucleotides supply RNA synthesis; ATP and GTP also serve as substrates in translation-related reactions.Book pp. 499–502
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
None of this group’s proteins appear in the information, signaling, regulation, machine-signal or assembly lists.
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 were activated nucleotides produced with suitable stereochemistry, selectivity and compatibility with polymer copying?
What needs explaining. Explain precursor production, polymer-compatible nucleotide chemistry and supply or salvage before the complete modern network existed.
Hurdles
- H-NUC-1Feedstocks and synthesisThe problem. A nucleotide is a base, a ribose sugar and a phosphate joined in a fixed way. Cells make them through about forty enzymes.Why it is hard. Laboratory routes reach them from different starting chemicals in separate, purified steps carried out in sequence by the chemist; those conditions are not found together in one natural setting.Chemistry before lifeStage 2: One step shown on its ownShown: Separate laboratory routes give pyrimidine and purine nucleotides from simple starting materials, with steps carried out one after another by the chemist.In the books: 130 open problems on nucleotide metabolism ↗
- H-NUC-2Correct connectionsThe problem. Only one of many possible linkages is used: the base on carbon 1 of ribose in the β-furanose form, and phosphate links between carbons 3 and 5.Why it is hard. Chemical mixtures give many alternative linkages and ring forms, and the wrong ones are produced alongside the right one.Chemistry before lifeStage 2: One step shown on its ownShown: Some routes favour the correct sugar–base attachment (Becker et al. 2016).In the books: 130 open problems on nucleotide metabolism ↗
- H-NUC-3One-handednessThe problem. RNA and DNA use only D-ribose.Why it is hard. Synthesis gives both hands. Mixed-hand nucleotides interfere with template copying, so purity is needed before copying works well (Joyce et al. 1984).Chemistry before lifeStage 1: Ingredients made under plausible early-Earth conditionsIn the books: 130 open problems on nucleotide metabolism ↗
- H-NUC-4Activation and stabilityThe problem. Nucleotides must be activated before they join; cells make triphosphates (ATP, GTP, CTP, UTP) with kinases.Why it is hard. Activated nucleotides break down in water within hours to days, and RNA itself hydrolyses faster at the high temperatures where Aquifex lives.Molecular machinesStage 2: One step shown on its ownShown: Activated cyclic phosphates appear in the 2009 pyrimidine route.In the books: 130 open problems on nucleotide metabolism ↗
- H-NUC-5CopyingThe problem. Copying a sequence needs activated monomers, a template, a start, strand separation and continuous resupply.Why it is hard. Copying without enzymes has worked only for short stretches, and the copies stay bound to their templates.Information and controlStage 2: One step shown on its ownShown: Short RNA templates have been copied without enzymes, but not over repeated rounds.In the books: 130 open problems on nucleotide metabolism ↗
Scope. A nucleotide is not a genetic instruction by itself. The sequence, copying behavior, and functional consequences of polymers must also be explained.
Experimental progress. Experiments in Bacillus show that the nucleotide signal (p)ppGpp binds the regulator PurR and changes control of purine biosynthesis during amino acid starvation.
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.
Observations. Carbon and nitrogen precursors supply RNA, DNA and energy-carrier synthesis. Salvage routes can recover material from nucleotide turnover where those pathways are present.
Hallmarks that apply.
- H24 Metabolic integration: Carbon and nitrogen precursors supply RNA, DNA and energy-carrier synthesis.
- H35 Recycling and waste management: Salvage routes can recover material from nucleotide turnover where those pathways are present.
- H27 Material selection: Specific catalysts distinguish substrates in nucleotide precursor chemistry.
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 Nucleotide Metabolism, with its scientific references.
How it was discovered
- 1869Friedrich Miescher isolates “nuclein”, later known as DNA, from white blood cells.Miescher, Hoppe-Seyler’s Medicinisch-chemische Untersuchungen 4:441–460 (1871)
- 1953Watson and Crick propose the double-helix structure of DNA.Watson & Crick, Nature 171:737–738 (1953)
- 1960Joan Oró makes adenine, one of the bases of DNA and RNA, from ammonium cyanide.Oró, Biochemical and Biophysical Research Communications 2:407–412 (1960)
- 2009Powner, Gerland and Sutherland make activated pyrimidine nucleotides from simple starting materials by a new route.Powner, Gerland & Sutherland, Nature 459:239–242 (2009)
- 2016Becker and colleagues report a route that joins purine bases to ribose at the correct position.Becker et al., Science 352:833–836 (2016)
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:
- Nucleotide Metabolism: system page · full description · origins