The Origin of Life

Index to this page

Abiotic Synthesis of Organic Molecules
Assembling Polymers
- An RNA Beginning?
Reproduction?
The First Cell?
The Last Universal Common Ancestor (LUCA)?
Creating Life?

To account for the origin of life on our earth requires solving several problems:

How the organic molecules that define life, e.g. amino acids, nucleotides, were created;
How these were assembled into macromolecules, e.g. proteins and nucleic acids, — a process requiring catalysts;
How these were able to reproduce themselves;
How these were assembled into a system delimited from its surroundings (i.e., a cell).

A number of theories address each of these problems.

Abiotic Synthesis of Organic Molecules

As for the first, three scenarios have been proposed: organic molecules

were synthesized from inorganic compounds in the atmosphere
rained down on earth from outer space
were synthesized at hydrothermal vents on the ocean floor

1. Miller's Experiment

Stanley Miller, a graduate student in biochemistry, built the apparatus shown here. He filled it with

water (H₂O
methane (CH₄)
ammonia (NH₃) and
hydrogen (H₂)
but no oxygen

He hypothesized that this mixture resembled the atmosphere of the early earth. (Some are not so sure.) The mixture was kept circulating by continuously boiling and then condensing the water.

The gases passed through a chamber containing two electrodes with a spark passing between them.

At the end of a week, Miller used paper chromatography to show that the flask now contained several amino acids as well as some other organic molecules.

In the years since Miller's work, many variants of his procedure have been tried. Virtually all the small molecules that are associated with life have been formed:

17 of the 20 amino acids used in protein synthesis, and
all the purines and pyrimidines used in nucleic acid synthesis.
But abiotic synthesis of ribose — and thus of nucleotides — has been much more difficult. However, success in synthesizing pyrimidine ribonucleotides under conditions that might have existed in the early earth has recently (Nature 14 May 2009) been reported.

One difficulty with the primeval soup theory is that it is now thought that the atmosphere of the early earth was not rich in methane and ammonia — essential ingredients in Miller's experiments.

2. Molecules from outer space?

The Murchison Meteorite

Representative amino acids found in the Murchison meteorite. Six of the amino acids (blue) are found in all living things, but the others (yellow) are not normally found in living matter here on earth. The same amino acids are produced in discharge experiments like Miller's.
Glycine	Glutamic acid
Alanine	Isovaline
Valine	Norvaline
Proline	N-methylalanine
Aspartic acid	N-ethylglycine

This meteorite, that fell near Murchison, Australia on 28 September 1969, turned out to contain a variety of organic molecules including:

purines and pyrimidines
polyols — compounds with hydroxyl groups on a backbone of 3 to 6 carbons such as glycerol and glyceric acid. Sugars are polyols.
the amino acids listed here. The amino acids and their relative proportions were quite similar to the products formed in Miller's experiments.

The question is: were these molecules simply terrestrial contaminants that got into the meteorite after it fell to earth.

Probably not:

Some of the samples were collected on the same day it fell and subsequently handled with great care to avoid contamination.
The polyols contained the isotopes carbon-13 and hydrogen-2 (deuterium) in greater amounts than found here on earth.
The samples lacked certain amino acids that are found in all earthly proteins.
Only L amino acids occur in earthly proteins, but the amino acids in the meteorite contain both D and L forms (although L forms were slightly more prevalent).

The ALH84001 meteorite

This meteorite arrived here from Mars. It contained not only a variety of organic molecules, including polycyclic aromatic hydrocarbons, but — some claim — evidence of microorganisms as well.

Furthermore, there is evidence that its interior never rose about 40° C during its fiery trip through the earth's atmosphere. Live bacteria could easily survive such a trip.

Link to a discussion of the possibility of life on Mars and more on the ALH84001 meteorite.

Organic molecules in interstellar space

Astronomers, using infrared spectroscopy, have identified a variety of organic molecules in interstellar space, including

methane (CH₄),
methanol (CH₃OH),
formaldehyde (HCHO),
cyanoacetylene (HC₃N) (which in spark-discharge experiments is a precursor to the pyrimidine cytosine).
polycyclic aromatic hydrocarbons
as well as such inorganic building blocks as carbon dioxide (CO₂), carbon monoxide (CO), ammonia (NH₃), hydrogen sulfide (H₂S), and hydrogen cyanide (HCN).

Laboratory Synthesis of Organic Molecules Under Conditions Mimicking Outer Space

There have been several reports of producing amino acids and other organic molecules by taking a mixture of molecules known to be present in interstellar space such as:

ammonia (NH₃)
carbon monoxide (CO)
methanol (CH₃OH) and
water (H₂O)
hydrogen cyanide (HCN)

and exposing it to

a temperature close to that of space (near absolute zero)
intense ultraviolet (uv) radiation.

Whether or not the molecules that formed terrestrial life arrived here from space, there is little doubt that organic matter continuously rains down on the earth (estimated at 30 tons per day).

3. Deep-Sea Hydrothermal Vents

Some deep-sea hydrothermal vents discharge copious amounts of hydrogen, hydrogen sulfide, and carbon dioxide at temperatures around 100°C. (These are not "black smokers".) These gases bubble up through chambers rich in iron sulfides (FeS, FeS₂). These can catalyze the formation of simple organic molecules like acetate. (And life today depends on enzymes that have Fe and S atoms in their active sites.)

Assembling Polymers

Another problem is how polymers — the basis of life itself — could be assembled.

In solution, hydrolysis of a growing polymer would soon limit the size it could reach.
Abiotic synthesis produces a mixture of L and D enantiomers. Each inhibits the polymerization of the other. (So, for example, the presence of D amino acids inhibits the polymerization of L amino acids (the ones that make up proteins here on earth).

Link to a discussion of enantiomers.

This has led to a theory that early polymers were assembled on solid, mineral surfaces that protected them from degradation, and in the laboratory polypeptides and polynucleotides (RNA molecules) containing about ~50 units have been synthesized on mineral (e.g., clay) surfaces.

An RNA Beginning?

All metabolism depends on enzymes and, until recently, every enzyme has turned out to be a protein. But proteins are synthesized from information encoded in DNA and translated into mRNA. So here is a chicken-and-egg dilemma. The synthesis of DNA and RNA requires proteins. So

proteins cannot be made without nucleic acids and
nucleic acids cannot be made without proteins.

The discovery that certain RNA molecules have enzymatic activity provides a possible solution. These RNA molecules — called ribozymes — incorporate both the features required of life:

storage of information
the ability to act as catalysts

Link to a discussion of ribozymes.

While no ribozyme in nature has yet been found that can replicate itself, ribozymes have been synthesized in the laboratory that can catalyze the assembly of short oligonucleotides into exact complements of themselves. The ribozyme serves as both

the template on which short lengths of RNA ("oligonucleotides" are assembled following the rules of base pairing and
the catalyst for covalently linking these oligonucleotides.

(The figure is based on the work of Green and Szostak, Science 258:1910, 1992.)

In principal, the minimal functions of life might have begun with RNA and only later did

proteins take over the catalytic machinery of metabolism and
DNA take over as the repository of the genetic code.

Several other bits of evidence support this notion of an original "RNA world":

Many of the cofactors that play so many roles in life are based on ribose; for example:
- ATP
- NAD
- FAD
- coenzyme A
- cyclic AMP
- GTP
In the cell, all deoxyribonucleotides are synthesized from ribonucleotide precursors.
Many bacteria control the transcription and/or translation of certain genes with RNA molecules (Link to "riboswitches") , not protein molecules.

Reproduction?

Perhaps the earliest form of reproduction was a simple fission of the growing aggregate into two parts — each with identical metabolic and genetic systems intact.

The First Cell?

To function, the machinery of life must be separated from its surroundings — some form of extracellular fluid (ECF). This function is provided by the plasma membrane.

Today's plasma membranes are made of a double layer of phospholipids. They are only permeable to small, uncharged molecules like H₂O, CO₂, and O₂. Specialized transmembrane transporters are needed for ions, hydrophilic, and charged organic molecules (e.g., amino acids and nucleotides) to pass into and out of the cell.

However, the same Szostak lab that produced the finding described above reported in the 3 July 2008 issue of Nature that fatty acids, fatty alcohols, and monoglycerides — all molecules that can be synthesized under prebiotic conditions — can also form lipid bilayers and these can spontaneously assemble into enclosed vesicles.

Unlike phospholipid vesicles, these

admit from the external medium charged molecules like nucleotides
admit from the external medium hydrophilic molecules like ribose
grow by self-assembly
are impermeable to, and thus retain, polymers like oligonucleotides.

These workers loaded their synthetic vesicles with a short single strand of deoxyguanosine (dC) structured to provide a template for its replication. When the vesicles were placed in a medium containing (chemically modified) dG, these nucleotides entered the vesicles and assembled into a strand of Gs complementary to the template strand of Cs.

Here, then, is a simple system that is a plausible model for the creation of the first cells from the primeval "soup" of organic molecules.

The Last Universal Common Ancestor (LUCA)?

The 3 kingdoms of contemporary life — archaea, bacteria, and eukaryotes — all share many similarities of their metabolic and genetic systems [Link]. Presumably these were present in an organism (or organisms) that were ancestral to these groups: the "LUCA". Although there are not enough data at present to describe LUCA, comparative genomics and proteomics reveal a closer relationship between archaea and eukaryotes than either shares with the bacteria. (Except, of course, for the mitochondria and chloroplasts that eukaryotes gained later from bacterial endosymbionts [Link].)

Creating Life?

When I headed off to college (in 1949), I wrote an essay speculating on the possibility that some day we would be able to create a living organism from nonliving ingredients. By the time I finished my formal studies in biology — having learned of the incredible complexity of even the simplest organism — I concluded that such a feat could never be accomplished.

Now I'm not so sure.

Several recent advances suggest that we may be getting close to creating life. (But note that these examples represent laboratory manipulations that do not necessarily reflect what may have happened when life first appeared.)

Examples:

The ability to created membrane-enclosed vesicles that can take in small molecules and assemble them into polymers which remain within the "cell" (as described above).
The ability to assemble functional ribosomes — the structures that convert the information encoded in the genome into the proteins that run life — from their components.
Assembling and Swapping Genomes.
In 2008, scientists at the J. Craig Venter Institute (JCVI) reported (in Science 29 February 2008) that they had succeeded in synthesizing a complete bacterial chromosome — containing 582,970 base pairs — starting from single deoxynucleotides. The entire sequence of the genome of Mycoplasma genitalium was already known [Link]. Using this information, they synthesized some 10,000 short oligonucleotides (each about 50 bp long) representing the entire genitalium genome and then — step by step — assembled these into longer and longer fragments until finally they had made the entire circular DNA molecule that is the genome.

Could this be placed in the cytoplasm of a living cell and run it?

The same team showed in the previous year (see Science 3 August 2007) that they could insert an entire chromosome from one species of mycoplasma into the cytoplasm of a related species and, in due course, the recipient lost its own chromosome (perhaps destroyed by restriction enzymes encoded by the donor chromosome) and began expressing the phenotype of the donor. In short, they had changed one species into another. But the donor chromosome was made by the donor bacterium, not synthesized in the laboratory. However, there should be no serious obstacle to achieving the same genome transplantation with a chemically-synthesized chromosome and we may hear about this soon.

So stay tuned!

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27 May 2009