A2.1 Origins of cells

The Earth formed about 4.5 billion years ago (more precisely, about 4.54). Its surface was at first molten, but within a few hundred million years it had cooled enough for liquid water to collect in oceans. The atmosphere came mainly from gases released by volcanoes. Conditions were very different from today.

Carbon compounds without life

These conditions supplied both raw materials (CO₂, CH₄, N₂, water and other small molecules) and plenty of energy (UV light, lightning, volcanic heat and hydrothermal vents). Energy breaks bonds in simple molecules and lets new ones form, so a variety of carbon compounds could have formed spontaneously by chemical processes. Dissolved in rain, these could have accumulated in seas and pools — the idea of a pre-biotic “soup” proposed by Aleksandr Oparin and J. B. S. Haldane in the 1920s.

These processes do not happen now for two reasons:

• Free oxygen in today’s atmosphere would oxidize and break down such molecules.
• Any organic molecules that did form would quickly be consumed by living organisms, mainly microbes.

UV light was a mixed blessing: it can drive useful reactions, but it also breaks molecules apart. Places shielded from UV, such as deep water, would have helped fragile molecules to survive.

Deciding exactly what counts as “living” is harder than it seems. A useful way to think about it is that living things are self-sustaining:

• They keep themselves in a highly ordered state, which needs a continual supply of energy from outside (light or chemical energy). This is metabolism.
• They take in materials (nutrition), get rid of waste (excretion), grow, respond to their surroundings and keep internal conditions within limits (homeostasis).
• They repair damage and reproduce, passing on the information needed to stay organized (heredity), so populations can evolve.

Non-living things may show some of these properties — a crystal grows, a fire uses fuel and spreads — but not all of them together.

Why the cell is the smallest unit

An individual organism is clearly alive, and so is each of its cells: a single cell can carry out all the functions of life. Unicellular organisms are whole organisms consisting of one cell (see A2.2 Cell structure). But the parts of a cell, such as a ribosome, a mitochondrion or a molecule of DNA, cannot sustain themselves if they are removed from the cell. So the cell is the smallest unit of self-sustaining life.

Why viruses are considered non-living

Viruses do have genes and they evolve, which is why some biologists argue they are on the borderline of life. But because they depend completely on a host cell for every life process, they are usually classed as non-living.

Today, cells are only ever produced by the division of pre-existing cells — one of the main ideas of cell theory. Pasteur’s experiments in the 1860s showed that microorganisms do not appear in sterile broth unless it is exposed to living cells, ending the old idea of spontaneous generation. Yet life has not always existed on Earth, so at some point the first cells must have arisen from non-living matter. Cells are so complex that this must have happened as a long series of small chemical steps, not in a single event.

Four things the first cells needed

A plausible order is: simple carbon compounds → polymers → self-replicating molecules → molecules enclosed in a membrane, giving a protocell.

Testing hypotheses about the origin of life

Scientific claims must be testable: it must be possible, at least in principle, to find evidence that would show them to be false. Hypotheses about the origin of cells are particularly hard to test:

• The exact conditions on pre-biotic Earth are unknown, so they cannot be reproduced exactly in a laboratory.
• Protocells were tiny, soft and had no hard parts, so they are very unlikely to have fossilized.
• Almost all rocks from that time have since been destroyed by erosion or altered by heat and pressure.

Scientists therefore test individual steps — can amino acids form, can a membrane assemble, can RNA catalyse a reaction — under conditions that seem plausible. A positive result shows that a step is possible, not that it is what actually happened.

In 1952 Stanley Miller, working in Harold Urey’s laboratory in Chicago, tested the hypothesis that the conditions on early Earth could produce carbon compounds without life. At the time, Urey argued that the early atmosphere was strongly reducing: rich in hydrogen-containing gases and without free oxygen.

The apparatus

• A flask of boiling water represented the oceans and supplied water vapour.
• A second, larger flask contained methane, ammonia and hydrogen, representing the atmosphere.
• Electric sparks between two electrodes represented lightning, supplying energy.
• A condenser cooled the gases so that water and dissolved products condensed, like rain.
• The liquid collected in a U-shaped trap, from which samples could be taken, and then flowed back to the boiling flask, so material circulated continuously.

Results

Within a day the water turned pink, and after a week it was deep red-brown. Analysis by chromatography showed it contained several amino acids, including glycine and alanine, as well as other organic compounds. Re-analysis of Miller’s stored samples in 2008, with much more sensitive methods, found more than 20 amino acids.

Evaluation

Organic molecules may still have formed on early Earth in places where conditions were locally reducing, such as volcanic plumes and hydrothermal vents, and some arrived in meteorites.

A cell needs a boundary. Without one, the products of any useful reactions would simply diffuse away, and molecules that worked well together could not stay together.

Fatty acids assemble themselves

A fatty acid has a long hydrocarbon chain, which is hydrophobic, with a carboxyl group (–COOH) at one end, which is hydrophilic. Molecules like this, with a hydrophilic part and a hydrophobic part, are amphipathic. In water they coalesce (come together) spontaneously, because this keeps the hydrocarbon chains away from water:

1. Above a critical concentration they form micelles: tiny spheres made of a single layer of molecules, with the carboxyl heads facing the water and the tails packed together in the centre.
2. Under suitable conditions — for example a pH close to neutral or slightly alkaline, where some carboxyl groups are ionized (–COO⁻) and some are not — they pack instead into a bilayer: two layers with the tails facing inwards.
3. A flat sheet of bilayer still has edges where tails touch water. The sheet curves and closes into a hollow sphere, so there are no edges left. The result is a vesicle: a spherical bilayer enclosing water.

No enzymes and no energy input are needed. Fatty acids can form without life — they have been found in meteorites, and laboratory simulations of hydrothermal vent conditions produce them — so vesicles could have formed in the seas and pools of pre-biotic Earth.

Why a compartment matters

• Internal chemistry can differ from outside: concentrations of molecules, and conditions such as pH, can be different inside the vesicle.
• Molecules such as RNA are kept together, so the products of one molecule can benefit the molecules near it, and they are passed on together when the vesicle divides.
• The protocell becomes a unit that natural selection can act on.

In laboratory experiments, fatty acid vesicles can grow by taking in more fatty acid molecules and divide into smaller vesicles. Their membranes are leakier than phospholipid membranes, so small molecules such as nucleotides can get in while larger RNA molecules stay trapped. Phospholipids, with two tails, form tougher, less permeable bilayers and probably replaced fatty acids later (see B2.1 Membranes and membrane transport).

In cells today, information and catalysis depend on each other. DNA holds the genes, but copying DNA and expressing its genes needs protein enzymes; proteins, in turn, can only be made using the information in DNA. Which came first? The RNA world hypothesis suggests that, before DNA and proteins, RNA did both jobs.

RNA can store and copy information

RNA is a nucleic acid (see A1.2 Nucleic acids). Its sequence of bases (A, C, G and U) can carry genetic information. A single strand can act as a template: free nucleotides pair with it by complementary base pairing (A with U, G with C) and can be joined into a new strand, so the sequence is copied. Some viruses still use RNA rather than DNA as their genetic material.

RNA can act as a catalyst

A single RNA strand can fold back on itself, held by base pairing between different parts of the strand, into a specific three-dimensional shape. Some folded RNAs have an active site and catalyse reactions; these are ribozymes. They were discovered in the early 1980s by Thomas Cech and Sidney Altman. In the laboratory, ribozymes have been evolved that can join nucleotides to copy short RNA templates, though none can yet copy itself completely.

Clues that remain in cells today

• The ribosome is still a ribozyme: during translation, peptide bonds are formed by ribosomal RNA in the large subunit, not by its proteins.
• Many coenzymes, including ATP, NAD and coenzyme A, contain ribonucleotide parts.
• Cells make DNA nucleotides by modifying RNA nucleotides, which fits RNA coming first.

Later, DNA took over information storage because it is more stable: deoxyribose lacks the reactive –OH group on carbon 2′, and the double helix protects the bases. Proteins, built from 20 different amino acids, took over most catalysis because they are more versatile catalysts. The main difficulty for the hypothesis is explaining how ribonucleotides first formed and joined, although chemists have found plausible pre-biotic routes to some of them.

All organisms alive today — bacteria, archaea and eukaryotes — are thought to be descended from a single ancestral population, the last universal common ancestor (LUCA). LUCA was already a fairly complex cell, with ribosomes, a membrane and probably DNA genes. It was not the first form of life.

Evidence for a common ancestor

Most of these features are arbitrary or complex, so it is much more likely that they were inherited from one ancestor than that they evolved separately many times. See A3.2 Classification and cladistics for how sequence comparisons are used to classify the three domains.

Other forms of life became extinct

Life may have originated more than once, or early life may have diversified into many lineages, perhaps even with different genetic codes. If so, all but one lineage became extinct, probably because they were outcompeted by LUCA and its descendants, which were better at obtaining resources. Only LUCA’s line has descendants today, which is why only one genetic code survives.

No one can observe the origin of life, so its date has to be estimated from indirect evidence. Each method has uncertainties, which is why published dates differ.

1. Fossils

Stromatolites are layered rock mounds built by mats of microorganisms that trap sediment and cause minerals to precipitate. Fossil stromatolites in the Pilbara region of Western Australia are about 3.4–3.5 billion years old and are the oldest widely accepted fossils. The rocks are dated by radiometric dating. Claims of older stromatolites and microfossils exist but are disputed, because similar structures can form without life.

2. Isotope ratios

The enzymes organisms use to fix carbon take up the lighter isotope, ¹²C, slightly faster than ¹³C. So carbon that has passed through living things has a low ¹³C/¹²C ratio compared with carbon in CO₂ or carbonate rocks. Graphite with this signature in 3.7 billion-year-old rocks from Isua, Greenland, suggests life by then. A graphite flake inside a 4.1 billion-year-old zircon from Jack Hills, Western Australia, has a similar ratio, but this single sample is disputed, as some non-living processes can also produce light carbon.

3. Molecular clock

The number of differences between the DNA or protein sequences of two groups increases with the time since they diverged. Calibrated with fossils of known age, the rate can be used to estimate when lineages split, and so to estimate the date of LUCA. Estimates have wide error margins; a large study published in 2024 suggested about 4.2 billion years ago, earlier than the oldest accepted fossils.

An immense length of time

If the whole history of the Earth were squeezed into 24 hours, the oldest accepted fossils would date from before 6 a.m., oxygen would start to build up in the atmosphere at about 11 a.m., animals with hard parts would appear after 9 p.m., and modern humans would appear about 6 seconds before midnight. Life has been evolving for most of the Earth’s history.

Hydrothermal vents are places on the seafloor where water that has seeped into the crust and been heated comes back out, carrying dissolved minerals and reduced (unoxidized) chemicals. As this fluid meets cold seawater, minerals precipitate and build chimneys.

Why alkaline vents suit the origin of LUCA

• Energy and raw materials: H₂ from the vent fluid can react with CO₂ from seawater to make organic molecules, releasing energy, without light.
• Catalysts: the early ocean was rich in dissolved iron, so the walls of proposed Hadean alkaline vents would have contained iron–sulfur (FeS) minerals, unlike modern Lost City chimneys. These minerals resemble the iron–sulfur clusters at the active sites of many ancient enzymes.
• Compartments: networks of tiny pores in the chimneys could concentrate molecules, acting as natural compartments before membranes evolved.
• Gradients: thin mineral walls separate alkaline vent fluid from more acidic ocean water, creating a natural H⁺ gradient — similar to the H⁺ gradients that all cells use to make ATP.
• Protection from UV light, deep in the ocean.

The evidence

• Fossils in vent deposits: tiny tubes and filaments of iron oxide in rocks from the Nuvvuagittuq belt in Quebec, Canada, at least 3.77 billion years old, formed in seafloor hydrothermal vent precipitates. They look like the structures made by modern iron-oxidizing bacteria at vents, although whether they are truly fossils is debated.
• Conserved genes: a 2016 study compared millions of genes from bacteria and archaea and identified 355 families of proteins likely to have been present in LUCA. They include enzymes for living anaerobically, using H₂, fixing CO₂ and N₂, and an enzyme found only in organisms living at high temperatures. This fits a hot, anaerobic, H₂-rich environment like a hydrothermal vent. Chemoautotrophs at vents today still obtain energy in this way (see C4.2 Transfers of energy and matter).

Not all scientists agree. Some favour shallow hot springs or pools on land, where repeated drying and wetting helps monomers join into polymers. Evidence that LUCA lived at vents does not prove that life began there.