About 4.8 Gigayears (Giga = 109) B.P. (= before present) a huge but very thin cloud of dust and gas condensed under the influence of gravitation into a large ball of gas (the sun) surrounded by smaller lumps of denser matter (planets). Heat was released by the gravitational collapse and also by the radioactivity of some elements present in the original dust. This heat raised the temperature of the planets, including Earth, far above their present values.

Elemental Composition of the Universe & Earth

Atoms per 100,000

Element Universe Earth Crust Life

H 92,700 120 2,900 60,600

He 7,200 <0.1 <0.1 0

O 50 48,900 60,400 26,700

Ne 20 <0.1 <0.1 0

N 15 0.3 7 2,400

C 8 99 55 10,700

Si 2.3 14,000 20,500 <1

Mg 2.1 12,500 1,800 11

Fe 1.4 18,900 1,900 <1

The universe consists mostly of H plus He. The heavier elements together comprise about 0.1% of the total. Planets such as the earth are composed of trace impurities in the universe which have concentrated at one point. The Earth is mostly Fe, Mg, Si, and O, with the other elements contributing 5% of the total. Life originated as a result of chemical reactions occurring (largely) in the atmosphere followed by reactions in the primeval oceans and lakes.

The Lithosphere of the Earth

The lithosphere consists of the core, the mantle and the crust. The crust consists mostly of the silicates of Fe, Al, Ca, Mg, Na, and K. The mantle is mostly Fe and Mg silicate with a small amount of Fe and heavy metal sulfides. The core is mostly a molten mixture of Fe and Ni.

The Primitive Hydrosphere

Most of the present ocean water (possible up to 90%) derives from outgassing by volcanic activity, hot springs, etc. the primitive earth thus had much less surface water. During the first few hundred million years of the Earth's existence, the water was in the form of stream, condensing later as the Earth cooled off.

Ancient Atmospheres

Primary Atmosphere

Originally Earth had an atmosphere mostly of H2 plus He. However, the mass of the Earth was too small to hold these light gases and they were lost into space.

Secondary Atmosphere

The Earth then accumulated a secondary atmosphere, due partly to outgassing from volcanoes, and partly to the reaction of condensing water vapor (formed as the Earth cooled) with minerals such as nitrides (hence NH3), carbides (hence CH4, CO, etc.) and sulfides (hence H2S). There was no free oxygen (any free O2 would have reacted with P, Si and metals such as molten iron to give minerals e.g. iron oxides, silicates, phosphates, etc.).

Volcanic Outgassing

Volcanic activity was much greater on the hotter primitive Earth. Volcanic gas consists mostly of steam (95%) and variable amounts of CO2, N2, SO2, H2S, S, HCl, B2O3, and smaller quantities of H2, CH4, SO3, NH3 and HF but no O2. Carbon dioxide is always the second major component (up to 4%).

Tertiary Atmosphere

The present atmosphere is of biological origin. Reactive gases such as NH3, CH4, etc., have been consumed. The inert components (N2, traces of Ar, Xe, etc.) remained unchanged and large amounts of oxygen have been produced by photosynthesis. This change did not occur until the evolution of the O2 evolving variant of photosynthesis, first seen in the cyanobacteria, about 2.5 Gyr B.P. The O2 content of the atmosphere reached 1% about 800 Myr B.P. and 10% about 400 Myr B.P. Today it is about 20%.

Evidence for the increase in O2 content of the atmosphere comes partly from the finding that rocks of different ages are oxidized to different extents. Thus rocks of age 1,800-2,500 Myr are found to contain UO2, FeS, ZnS and PbS and FeO, all of which are unstable in the presence of even small amouts of O2. Later rocks contain mostly Fe3+ rather than Fe2+, and more oxidized ores of U, Zn and Pb etc.

Time Scale for Origin of Planets and Life

Millions of Years Ago What Happened

Atmospheric Reactions

The primitive (secondary) atmosphere contained N2, H2O (vapor), NH3, H2S, CO and CO2. These reacted to give such small organic molecules as HCN and HCHO:

2CH4 + N2 ===> 2HCN +3H2

CO + NH3 ===> HCN +H2O

The HCN and HCHO continued to react and further products were formed e.g. in the atmosphere:

HCHO + NH3 ===> H2N-CH2OH ===> HN=CH2 + H2O

HN=CH2 + HCN ===> H2NCH2CN

In the primeval ocean:

H2NCH2-CN + 2H2O ===> H2NCH2COOH + NH3

This sequence of reactions (the Strecker synthesis) has formed glycine, the simplest amino acid. More complex reactions form more complex amino acids from other substrates. Replacement of NH3 with H2O vapor in the above reactions gives hydroxy acids (e.g. lactic acid) instead of amino acids.

These atmospheric reactions need a source of energy to drive them. On the primeval Earth there were a variety of possible energy sources.

Relative Energy Source of Energy

1000 a) Sunlight. 98% of sunlight photons are visible and of insufficient energy to promote chemical reactions. Of the ultraviolet-photons (<300 nm wavelength) only about 1% (those <200nm) would be highly effective. Today most of the ultraviolet is screened out by the ozone (O3) layer. In primeval times there was no ozone and UV rays penetrated freely.

100 b) Electric discharges (corona discharges, lightning).

70 c) Natural radioactivity. Most of the high energy radiation (i.e. more energetic than UV) comes from the interior of the earth. Uranium-238 and -235 and Thorium-232 give off alpha and gamma radiation. Potassium 40 is a gamma and beta emitter only. 4000 Myr ago there was about 4 times the amount of Uranium-238 and the overall radioactivity was perhaps three times the present level.

25 d) Shock waves in the atmosphere (from thunder and meteorite impact).

5 e) Solar wind.

5 f) Volcanic heat. Important locally.

1. g) Cosmic rays.

The relative energy is per unit surface area of the earth per year. (Ultraviolet is set to 1000). It is important to realize that molecular O2 would have destroyed the products of primitive atmospheric reactions. As regards the origin of life O2 is a highly toxic molecule whereas HCN, H2S, CO, and HCHO are life promoting.

The Miller Experiment

The theory of the origin of life was put forward by the Russian biochemist Alexandr Oparin in the 1920's. In the 1950's, Miller mimicked the primitive Earth atmospheric reactions. A mixture of methane, ammonia and water vapor was subjected to a high voltage discharge (to simulate lightning). Organic compounds were formed and dissolved in a flask of water, where further reaction is possible. There are many variants of this experiment (different gas compositions, different energy sources, etc.). As long as oxygen is excluded the results are similar. First aldehydes (e.g. HCHO, CH3CHO) and cyanides (HCN, NC-CN) are formed and later a large variety of organic compounds, mostly acids. Note that genuine biological compounds are formed together with isomers which are not found in living cells. For example, sarcosine and beta-alanine are both isomers of alanine. About 15% of the methane is converted to soluble organic molecules and quite a lot more is converted to un-analysable organic tar. Typical products are:

Molecule Name Relative Yield

H-COOH formic acid 1000

H2N-CH2-COOH glycine 275

HO-CH2-COOH glycolic acid 240

H2N-CH(CH3)-COOH alanine 150

HO-CH(CH3)-COOH lactic acid 135

H2N-CH2CH2-COOH beta-alanine 65

CH3-COOH acetic acid 65

CH3-CH2-COOH propionic acid 55

CH3-NH-CH2-COOH sarcosine 20

HOOC-CH2CH2-COOH succinic acid 17

H2N-CO-NH2 urea 9

HOOC-CH2CH2CH(NH2)-COOH glutamic acid 2.5

HOOC-CH2CH(NH2)-COOH aspartic acid 1.7

Originally it was thought that the primitive secondary atmosphere contained mostly NH3 and CH4. However, it is likely that most of the atmospheric carbon was CO2 with perhaps some CO and the nitrogen mostly N2. The reasons for this are (a) volcanic gas has more CO2, CO and N2 than CH4 and NH3 and (b) UV radiation destroys NH3 and CH4 so that these molecules would have been short-lived. UV light photolyses H2O to H· and ·OH radicals. These then attack methane, giving eventually CO2 and releasing H2 which would be lost into space.

In practice gas mixtures containing CO, CO2, N2, etc. give much the same products as those containing CH4 and NH3 so long as there is no O2. The H atoms come mostly from water vapor. In fact, in order to generate aromatic amino acids under primitive earth conditions it is necessary to use less hydrogen-rich gaseous mixtures. Most of the natural amino acids, hydroxyacids, purines, pyrimidines, and sugars have been produced in variants of the Miller experiment.

Some differences worth noting are:

Phosphorus

One of the major problems of pre-biotic chemistry is how phosphorus could have entered into reactions. There is plenty of phosphorus available, but it is found as insoluble phosphate minerals.

a) Phosphates of Ca and other divalent metals are very insoluble, hence most of the phosphorus would precipitate as Ca phosphate derivatives e.g. fluoro-apatite Ca10(PO4)6F2

b) Most phosphorus experiments have used high concentrations of pyrophosphate or polyphosphoric acid and are therefore geologically implausible.

Synthesis and Destruction

Note that the same energy sources that produce organic molecules are also very effective at destroying them. Accumulation of organic material therefore requires removal of products from the reaction region - hence the imitation primeval ocean in the Miller experiment. Water shields molecules from UV and electric discharges. The survival of organic molecules on the primitive earth would have depended on their escape from UV radiation etc either by dissolution in seas or lakes or by adsorption to minerals. Organic molecules formed in the upper regions of the atmosphere would mostly have been destroyed again very quickly. Note that organic acids and in particular amino acids are ionic and therefore nonvolatile. Consequently once synthesized and safely in aqueous solution there is little tendency for such molecules to return to the atmosphere. The intermediates, such as aldehydes and cyanides are not only reactive but also volatile. Consequently these molecules do not accumulate as final products.

Primitive Earth Syntheses

Even today photochemical formation of HCHO occurs in the atmosphere and can be detected in rain. Condensation of formaldehyde under mildly alkaline conditions produces a vast variety of polymeric materials - the Formose reaction. Isomers of (CH2O)5 and (CH2O)6 are most frequent with tetramers and heptamers in smaller amounts. Most common biological sugars such as ribose, glucose etc. are found as products of the formose reaction, together with a wide range of isomers and derivatives.

c) Synthesis of Purines Adenine = C5H5N5 = (HCN)5

Adenine is a pentamer of hydrogen cyanide. Adenine is manufactured industrially in Japan by heat-polymerizing HCN. On the primitive earth a tetramer of HCN probably formed by successive condensations. This then rearranged under the influence of ultraviolet light to form one ring. A fifth HCN then condensed with this precursor to form the second ring. When HCN is heated in solution with NH3 a black tar is formed together with adenine as the major soluble aromatic product. The thermal mechanism shown below is probably slightly different from the UV promoted pathway. Note that ammonia is needed as a catalyst. It takes part in the reaction but an equal number of ammonia molecules are released as are incorporated. Smaller amounts of guanine and other purine derivatives are also formed.

Extraterrestrial Biomolecules

a) Interstellar space. Radio frequency spectroscopy has found H2O, NH3, and organic molecules in interstellar dust clouds, i.e. in the type of material from which the solar system condensed. Representative molecules are HCHO, CO, HCN, HCOOH, CH3OH, HCHS (thioformaldehyde), CH3CN, HCC-CN (cyanoacetylene). In addition many ions and radicals are found e.g. OH, CH+, and CN. Silicon monoxide (SiO), which is not stable on Earth, and tiny grains of Silica are also found.

Note that interstellar dust clouds have a density about 10-14 of the Earth's atmosphere (at sea level). Two points of importance:

1) Interstellar concentrations of organic molecules are very low, consequently reactive molecules and unstable molecular fragments collide extremely rarely and so can survive

2) Interstellar space is heavily irradiated by UV which tends to produce radicals/ions from molecules. Thus complex molecules tend to be destroyed unless they are shaded by a large enough accumulation of interstellar dust.

b) Meteorites. There are two major classes - stony meteorites and metallic (iron) meteorites. The stony meteorites contain mostly silicates of Mg and Fe. A sub-class of these, the carbonaceous chondrites, contain in addition from 0.2 to 5% carbon, 1.8 to 6.7% sulfur and 0.1 to 22% water. Hydrocarbons, fatty acids, malonic acid, succinic acid, fumaric acid and amino acids have been found. The amino acids are a racemic D, L mixture and contain non-protein amino acids. These organic compounds are therefore probably extraterrestrial in origin.

c) Panspermia. Panspermia is the theory that the earth was seeded with primitive life forms from other planets where life actually arose. This merely puts the origin of life backwards to another earth-like planet. It might be possible for very small, radiation resistant spores to travel around the universe under light pressure or for contamination by space travel to occur.

Polymerization and the Primitive Soup

The molecules formed above would dissolve in the primeval ocean, so forming the "primitive soup." Estimates suggest that the primeval oceans may have contained as much as 5-10% organic materials. Other estimates are much lower and suggest that organic material was concentrated by evaporation in tidal basins or in inland lakes etc.

Polymerization to give biological macromolecules usually requires the removal of H2O. Clearly, H2O was in excess in the oceans and removal of H2O from molecules was therefore unfavorable. This leads to a requirement for condensing agents which withdraw water. Several possible primeval condensing agents have been proposed:

a) Cyanides including HCN itself and derivatives such as cyanogen (NC-CN), hydrogen cyanate (HCNO) and cyanoacetylene (HCºC-CN).

Consider the reaction: A-OH + H-B ===> A-B + HO

This can be pulled over by reaction with a cyanide derivative R-CN:

A-OH + R-CºN ===> A-O-C=NH ===> A-B + H2N-CO-R
|
R + B-H

b) Condensing agents derived from phosphate. Inorganic polyphosphates would have been present in primeval times (formed by volcanic heat from phosphates for example). Polyphosphates can react with many organic molecules to give organic phosphates. Amino acids give two possible products. Acyl phosphates have the phosphate group attached to the carboxyl group of the amino acid (NH2CHRCO-OPO3H2) Phosphoramidates have it attached to the amino group of the amino acid (H2O3P-NH-CHR-COOH).

Gentle heating or irradiation will then give polypeptides. Modern life uses acyl phosphate derivatives during protein synthesis. However, laboratory synthesis of DNA uses phosphoramidates. Analogous reactions can give AMP from adenine and polynucleotides can then form by polymerization.

c) Clay and apatite minerals. Absorption of monomers to catalytic minerals promotes many reactions. Montmorillonite clay will condense aminoacids to form polypeptides up to 200 residues long. Note that whereas biological proteins are bonded using only the alpha-NH2 and alpha-COOH groups of amino acids these "primeval polypeptides" contain substantial numbers of bonds involving side chain residues.

d) Dry heat. Proteinoids can be formed by heating amino acid mixtures at around 150°C for a few hours. Dry heat would have occurred when pools left behind by a changing coastline evaporated, or near volcanoes. These primeval proteinoids contain up to 250 amino acids and can be partially digested by some proteolytic enzymes. Several enzymatic activities have been detected in thermal proteinoids, although not anywhere near as efficient as modern enzymes. Such activities include esterase (versus nitrophenyl acetate) which shows Michaelis-Menten kinetics and a pH optimum, and only occurs if histidine residues are present. Proteinoids containing heme can be made by including heme in the mixture before heating and exhibit peroxidase activity. Zinc containing proteinoids show ATPase activity.

Reaction Special Characteristics Substrate

esterase histidine p-nitrophenyl-phosphate

ATPase Zn2+ ATP

amination and Cu2+ alpha-ketoglutarate

deamination ´glutamate

peroxidase and heme, basic proteinoids H2O2 and H-donors e.g.

catalase hydroquinone, NADH

decarboxylation basic proteinoids oxaloacetate

acidic proteinoids pyruvate

Informational Macromolecules

Biological information is passed on by template-specific polymerization of nucleotides. A mixture of polyphosphate, purine and pyrimidines will produce random nucleic acid chains if ribose or deoxyribose is included. One problem, not yet solved is that life uses 3', 5' linked nucleic acid whereas primeval type syntheses give RNA molecules with a mixture of linkages, but mostly 2', 5'. (Deoxyribose has no 2'-OH so cannot give 2', 5' links).

When an RNA template is incubated with a mixture of nucleotides, plus a primeval condensing agent, a conplementary piece of RNA is synthesized. This nonenzymatic reaction is catalyzed by lead ions, with an error rate of about 1 wrong base in 10. With zinc ions, a great improvement is seen and lengths of up to 40 bases are produce with an error rate of about 1 in 200. All modern day RNA and DNA polymerases contain zinc. If a 3', 5' linked RNA template is used about 75% of the newly formed RNA is 3', 5' linked. However, this does not surmount the problem that the original formation of RNA type polymers favors the non-biological 2', 5' linkage very heavily. It is thought that RNA probably provided the first informational molecule and that DNA is a later invention designed to store information in a more stable and more accurate form.

The appearance of informational macromolecules has given rise to three alternative theories:

Asymmetry

Life uses only L-amino acids to make proteins and mostly D-sugars. Primeval mixtures were racemic. Proteins could form from D-amino acids just as well as from L-amino acids. What is important is that a stable protein structure (in particular alpha-helices, beta-sheets) requires amino acids all of one configuration NOT a mixture. Although assymetry was therefore required, the choice of L- over D- for amino acids (and vice versa for sugars) was most likely quite arbitrary. Once the choice had been made, life was committed to the chosen isomer.

Coacervates, Proteinoid Microspheres & Liposomes

Oparin, who first outlined the theory of the chemical origin of life, worked on coacervates. Coacervation is a process occurring in aqueous solutions of highly hydrated polymers. Two phases separate spontaneously and one of these may consist of hollow, polymer-rich, microscopic droplets suspended in the surrounding medium. Gums are anionic polysaccharides from plants and bind well to positive or neutral proteins. Protein plus polysaccharide or RNA will often form coacervates and enzymes can be trapped inside the droplets when they form.

Materials diam (mM) mass (picog) % polymer in droplets

Albumin plus Gum 3 to 6 5 to12 20 to 35

Histone plus Gum 3 to 7 3 to 20 8 to 15

Histone plus RNA 1 to 15 2 to 100 4 to 50

For example, when Oparin made coacervates with NADH dehydrogenase trapped inside they would catalyse the reduction of methyl red by NADH. The substrates diffused in and the products diffused out. Coacervates with glycogen phosphorylase trapped inside convert glucose-1-phosphate (from the aqueous medium) into starch (=glycogen) which accumulates inside the coacervate droplets. The starch merges with the wall of the droplet which therefore increases in size and eventually divides into two. This continues until the enzyme is too dilute to produce further growth by making starch. If both glycogen phosphorylase and amylase are trapped inside the same vesicle, starch is made by the glycogen phosphorylase and degraded to maltose by the amylase. The net result is a steady state in which no growth of the droplet occurs but glucose-1-phosphate is converted to maltose.

If hot solutions of thermal proteinoids are cooled under the correct conditions they produce microspheres, about 2 microns in diameter. These are sometimes hollow and have outer membranes of protein. Basic (i.e. positively charged) proteinoids selectively associate with RNA. When protein/RNA microspheres are incubated with amino acid adenylates they produce short polypeptide chains i.e. they act like primeval ribosomes.

Similar experiments can be done with vesicles made of lipids. When liposomes are made with lipids whose fatty acids are 10-12 carbons long they are leaky to small proteins and oligonucleotides. If the fatty acids are 14 carbons long they will allow small molecules (nucleotides etc) in or out, but small proteins and oligonucleotides cannot cross. When the fatty acids are 16-18 carbons long, the liposomes are impermeable even to small solutes. Polynucleotide phosphorylase can be trapped in liposomes. When lipids with C14 chains were used, and ATP was added it crossed the membrane. The enzyme converted it into oligonucleotides which were trapped inside the vesicle.