Under the Microscope / Dr William Reville:One of the greatest puzzles facing science is how life spontaneously arose on Earth from lifeless molecules almost 4 billion years ago.
The conventional hypothesis proposes that life began when a sturdy, information-rich, large molecule capable of making copies of itself first arose, possibly DNA, or more likely RNA. This is called the replicator-first hypothesis. But little progress has been made in simulating how this might have happened, and such an event might be almost impossibly improbable. An alternative hypothesis, described by Robert Shapiro in Scientific American(June 2007), the metabolism-first hypothesis, proposes that life began as a collection of small molecules interacting with each other in a network driven by a source of energy. Shapiro persuasively argues that this is a far more likely scenario.
DNA, the genetic material, is a large molecule made of four different kinds of building blocks called nucleotides, denoted by letter symbols A, T, G and C. These combine together end to end to form long strings and the DNA molecule is composed of two such strings wound around each other in a double helix. The As on one strand always pair with Ts on the other strand, and the Gs always pair with Cs. The sequence on either strand automatically specifies the sequence on the other and this is at the heart of the replication mechanism. When DNA copies itself, the two strands separate and each forms a template onto which nucleotides bind to form complementary strands, thereby forming two new molecules of DNA, each identical to the parent molecule.
However, the problem is that DNA alone is incapable of copying itself. It needs the assistance of several protein molecules in order to replicate. Proteins are also large molecules made from units called amino acids, of which there are 20 different kinds. The amino acids are joined end to end in long strings. Proteins carry out most of the work of the cell and there are thousands of different kinds of proteins, the identity of each type specified by its sequence of amino acids. Probably the most important proteins are catalysts called enzymes, which speed up the chemical reactions in the cell sufficiently to underpin life. The information that specifies what proteins are made in the cell is encoded in DNA.
You can see the problem now as regards the origin of life. The existence of proteins depends on information in DNA, and DNA can't copy itself without the assistance of proteins. Which came first - the chicken or the egg?
When the cell makes proteins the information encoded in DNA is translated into an amino acid sequence, but this is not done directly. First, the information in DNA is transcribed into information in another large molecule called RNA, also made of four different nucleotides. It is the RNA information that is directly translated into amino acid sequences in proteins. In the early 1980s, ribozymes - enzymes made of RNA that can catalyse their own synthesis - were discovered. This seemed to solve the chicken/egg conundrum. It was proposed that life began when self-copying RNA molecules first arose. In other words, an "RNA world" preceded the DNA world.
A landmark in origin-of-life research happened in 1953 when Stanley Miller passed spark discharges through a mixture of gases formulated to mimic the composition of the atmosphere of the early Earth. To his great excitement he found that this caused several amino acids to form, and it has subsequently been noted that amino acids are found in some meteorites that fell to earth. Nature easily forms amino acids, and it was assumed that all other building blocks are likewise assembled with similar ease. But this does not seem to be the case.
No nucleotides are formed in Miller-type experiments, and none are found in meteorites. A nucleotide is a much more complex molecule than an amino acid and contains about 10 carbon atoms. The simplest amino acids contain only two carbon atoms. Even if nucleotides could arise spontaneously in a chemical soup, there is a huge variety of ways they could join together other than the manner in which they do in DNA and RNA, but these various other ways could not underpin life.
And so, it is possible that any conceivable replicator-first scenario might be impossibly improbable.
The living cell is basically a bag containing complex sequences of chemical reactions that are interlinked and delicately controlled. The energy needed to drive this complex chemical machine is produced by oxidising (burning) sugar. It is possible to visualise, as Shapiro outlines, how life could have started when some simple chemical reactions became segregated from their surroundings, perhaps in soap-bubble like containers, these reactions driven by the chemical energy of other oxidation reactions. These little cells would have no genetic material as we understand it now - that is, no coded instructions that specify the chemistry. Rather the working chemistry itself would be the genetic material (just as a shopping list and the actual shopping items in the trolley represent the same information). Such cells could compete with each other and evolve by Darwinian mechanisms. In this metabolism-first scenario, based on a much better probability outlook, replicator molecules, probably in the form of simple RNA, would arise later in the history of life.
The replicator-first hypothesis relies on an event of such enormous improbability that, if it is correct, means we are probably alone in the universe. The metabolism-first hypothesis relies on a much more probable scenario. If this is how life arose, we are very likely to be sharing the universe with companions elsewhere.
William Reville is Associate Professor of Biochemistry and Public Awareness of Science Officer at UCC