Clearly, evolution of organisms must begin with evolution of the molecules of which they are built.

The evidence is substantial that a universal ancestral cell arose under conditions existing on the primitive earth of approximately four billion years ago.

• Authenticated fossils have been dated from 2.85 to 3.5 billion years ago {Brocks et al., Science, 1999, 285, 1033; Furnes et al., Science, 2004, 304, 578].

• The overall story is well told by Robert Hazen, "gen.e.sis: The Scientific Quest for Life's Origins", Joseph Henry Press,Washington, 2005. "Life Ascending", by Nick Lane, Norton, 2009, also has an excellent chapter on this.

Joyce [Nature, 2002, 418, 214] suggests the timeline:

Where did the small molecules for prebiotic chemistry come from?

Some possibilities:

Stanley Miller sent electrical discharges (simulating lightning) through a mixture of NH₃, CH₄, H₂O, and H₂

• He found amino acids, purines, and pyrimidines among the products [Science, 1953, 117, 528; J. Am. Chem. Soc., 1955, 77, 2351]

• More recent experimenters have used atmospheres that include CO₂, CO, and N₂, and used much more sensitive means of detecting trace products.

• Metal ions (Cu⁺⁺, Ni⁺⁺, Zn⁺⁺) also are components of some of these mixtures. Examples of the compounds formed are shown in the Table:

  Carboxylic Acids	Purine and Pyrimidine Bases	Amino Acids	Sugars	Miscellaneous
  Formic, Acetic, Propionic, Straight and branched C4 - C10, Glycolic, Lactic, Succinic	Adenine, Guanine, Xanthine, Hypoxanthine, Cytosine, Uracil	Glycine, Alanine, 2-Aminobutryic, Valine, Leucine, Isoleucine, Proline Aspartic, Glutamic, Serine, Threonine	Pentoses (especially ribose), hexoses, both straight and branched chain	Formaldehyde, HCN

• In addition, ribonucleotides and their oligomers, and oligomers of amino acids also form. Thus, many of the chemical components of living cells can form under prebiotic conditions.

An alternative: deep sea vents, which would be protected from the meteor bombardments of the early earth.

• Originally proposed by a graduate student at Oregon State, Sarah Hoffman [Oceanologica Acta, 1981, 4, 59; Orig. Life and Evol. Biosphere, 1985, 15, 327]

• The environment provides hot water, sulfur-rich minerals, and carbon dioxide

• The formation of metabolic species can be duplicated under pressure in the lab [Cody et al., Science, 2000, 289, 1337; Geochim. Cosmochim. Acta., 2001, 65, 3557]

• In 1969, a carbonaceous meteorite of cometary origin fell near Murchison, Australia, and substantial fragments of it were recovered.

• Careful dating (uranium decay series) gave an age of 4.9 x 10⁹ years

• Chemical examination revealed the presence of amino acids, purines, and pyrimidines

Does this imply the potential evolution of life elsewhere in the universe?

• Indeed, Sagan, Orgel, and others have suggested that such cometary matter may have "seeded" the early earth.

• The amino acids found on these meteorites contain an excess of the S enantiomer

• Pizzarello and Weber [Science, 2004, 303, 1151] have shown that sugars synthesized under prebiotic conditions in the presence of such amino acids display an enantiomeric excess of the correct sign

Orgel and others have suggested that the next step was the separate development of some energy-releasing pathways and replicating systems.

• Some basic metabolic pathways could have developed from existing, uncatalyzed, reactions of components of the "soup", perhaps in fatty acid micelles.

• Miller suggests a spontaneous energy-releasing pathway might be:
  glycine + NADH + ADP + P_i = acetate + NH₄⁺ + NAD⁺ + ATP

• Hydrolysis of thioesters is another possible energy-producing pathway.

Here is the so-called "Lost City, 7100 feet under the Atlantic Ocean, pH 9-11, T = 90 ^oC:

The Mid-Atlantic Ridge	Lost City, About 20 km East of the Ridge
Pinnacles of Carbonate Rock	A "Black Smoker"
Pictures from NOAA and University of Washington

The vents in these structures are full of bacteria, happily synthesizing hydrocarbons, sterols, and other organic molecules.

Copley and coworkers [Bioorganic Chemistry, 2007, 35, 430] have suggested a simple pathway for the formation of the necessary nucleotides:

• Needed inputs are: NH₃, formate, CO₂, glyoxalate, and ATP

At some point the replicating systems must come to occupy cells or cell-like structures. Two possibilities:

• Self-assembling micelles trap nucleotides, increasing concentration to allow oligomerization [Luisi et al., Origins Life and Evol. Biosphere, 1989, 19, 633; Ber. Bunsengesellschaft Physikal. Chemie, 1994, 98, 1160].

• RNA formation on clay surfaces has been demonstrated [Ferris et al., Science, 1992, 257, 1387; J. Am. Chem. Soc., 1993, 115, 12270].

RNA world then would develop in stages:

Excellent summaries of these pathways are provided by Martin and Russell [Phil. Trans. Royal Soc. Lond., B2003, 358, 59; B2007, 362,1887]

What is being suggested by these ideas and experiments is, of course, the unity of all life: the universal common ancestor.

Carl Woese [Proc. Nat. Acad. Sci., 1990, 87, 4576; 2000, 97, 8392] sought verification of this notion by sequencing ribosomal RNA, which has persisted at least since the RNA world. His results provide a "Tree of Life":