Tuesday, 16 September 2014

From Test Tube Baby To Test Tube Metabolism

A diagram elucidating the metabolism first and the components first approaches.
The origin of life is a thorny subject, but its study divides into two broad camps with different starting points: a components-first approach, looking at how proteins, lipids and nucleic acids could have formed in a pre-biotic environment. The other, a metabolism-first approach, looks at how an energy-generating chemical complex could have formed in the absence of the carefully controlled, enzyme directed pathways used by cells today.

A popular explanation of how things began is the RNA world hypothesis, which comes under the first camp. RNA is a molecule which could act as a precursor for DNA and as a catalyst for the synthesis of energy and proteins. A competing hypothesis is the iron-sulphur world, created by Gunter Wachtershauser, which examines how a combination of iron and sulphur catalysts, with products produced by hydrothermal vents, could create a primitive version of a metabolism. RNA has much to support its claims, but recently the iron sulphur hypothesis has gained momentum thanks to a happy accident.

A team of biologists led by Markus Ralser, from the University of Cambridge, were conducting a routine test of a bacterial growth medium. This involved running a sample of the medium through a mass spectrometer. It returned an unexpected result, the presence of the chemical signature of the molecule known as pyruvate. Pyruvate, the product of a metabolic pathway known as glycolysis, is the starting point of the energy-generating mechanism used by all cells. Yet the growth medium was devoid of living cells. So how was pyruvate present? The only possible explanation was that it had been generated in the absence of life by a series of organic reactions.

To investigate further, the researchers repeated the synthesis of the medium, incorporating compounds which simulated the conditions of the oceans in which life first evolved. The mixture was incubated at between 50 and 70 degrees Celsius to replicate temperatures found around hydrothermal vents. 'In the beginning we had hoped to find one reaction or two maybe, but the results were amazing,' said Ralser. 'We could reconstruct two metabolic pathways almost entirely.' Overall, 29 steps similar to those found in metabolic pathways were identified, in particular those involved in the glycolysis and pentose - 5 - phosphate pathways.

The former of these allowed for the formation of pyruvate, important for its role in energy generation. The latter, however, was even more intriguing as its product (pentose - 5 - phosphate) is a precursor compound needed to form RNA, which in turn could lead to the formation of DNA, an aid to the synthesis of enzymes and proteins. 'In our reconstructed version of the ancient Archean ocean, these metabolic reactions were particularly sensitive to the presence of ferrous iron which was abundant in the early oceans, and accelerated many of the chemical reactions that we observe. We were surprised by how specific these reactions were,' added Ralser.

Admittedly the reactions and reaction pathways observed were not identical to those used by cells, but they provide a highly detailed picture of how chemical systems may have acted as a precursor to true life forms. This is a massive leap forward in our understanding of the origin of life and metabolism. What makes this experiment all the more remarkable is that it was sparked by happenstance rather than direct inquiry.