Monday, June 27, 2016

LUCA, Creature of the Vent


(For part 1 of this series on the first two chapters, click here.)

Having outlined the problem in Part I of The Vital Question, Nick Lane narrows down the conditions for the origin of life in Part II. Chapter 3 is titled “Energy at life’s origin” and Chapter 4 is “The emergence of cells”.

In Chapter 3, Lane cuts straight to the chase by outlining six requirements for a cell, assumed to be the smallest “unit” of a living organism.
·      A supply of reactive carbon
·      Free energy to drive some sort of metabolism
·      Catalysts (to overcome the “right” kinetic barriers)
·      A method to excrete “waste” products
·      Compartmentalization
·      Informational material that is heritable

He skips past the details I really care about (the formation of primitive metabolic cycles involving a range of small organics), but no fault of his as we simply don’t know at this stage what might have constituted these cycles. That’s why it is an area of active research I’m engaged in. If the answers were known, this would be less interesting.

Lane’s goal is to quickly narrow the cradle of life to just one viable option (that we are aware of) – alkaline hydrothermal vents. The argument is made by quickly and effectively dismissing other possibilities suggested in the literature. First, he rules out an open primordial ocean/soup. This makes sense because concentrations of suitable organic molecules would be miniscule, and no interesting chemistry will take place. He then rules out freezing environments. Although useful for concentrating organics, a mechanism for continuous supply of the building blocks is lacking. That’s a problem.

What might the source of carbon be? Lane thinks CO2 is a good candidate (CO being too low in concentration), and there is some evidence that the amount of CO2 was significantly higher on the Hadean earth compared to today. His candidate reaction to form organics such as formate, formaldehyde, methanol, methane (this list represents increasingly reduced C1 molecules), is the reaction of CO2 and H2. The problem is that this reaction is not favorable within the same pH environment, however if there was a pH gradient then this might work. Lane calculates that the redox reaction is favorable if the oxidation of H2 took place at pH 10, and CO2 reduction to formaldehyde was at pH 6. His solution: An iron-sulfide semiconducting barrier that you might find in an alkaline hydrothermal vent. The outside of the vent has acidic waters (pH 5-7 has been suggested; I’ve even published a paper on this). The inside of the vent is alkaline.

There’s a nice vignette about the discovery of the Lost City alkaline hydrothermal vents of white smokers vindicating the predictions made by Martin Russell years before. Lane effectively argues against the black smokers (much hotter and more acidic) as the cradle of life. The higher temperatures and much more acidic conditions favor hydrolysis – it is hard to maintain any semblance of a short polymer (proteins, starches, DNA are all polymers) in this environment. Lane also enumerates characteristics of the milder white smokers that may allow both the concentration (via thermophoresis) and incubation of small organics. This could be the route to more complex molecules. He doesn’t specify details, and his group is building physical models to simulate these conditions to test his hypothesis. (That’s how science should work!) His model also ties in nicely with the proton pumps mentioned in Part 1.

Chapter 4 opens with the problem of lateral gene transfer in prokaryotes “erasing” the history that might otherwise be reconstructed through phylogenetics. (Bill Martin’s ‘amazing disappearing tree’ is used as an example.) Lane then enumerates some of the key differences between archaea and bacteria. What they share was likely present in the Last Common Universal Ancestor (LUCA). These include proteins and ribosome translational machinery, DNA and some form of transcription, and an ATP synthase – i.e. the ability to pump protons. However they differ in many other ways ranging from membrane composition to the DNA replication apparatus. Lane uses these odd similarities and dissimilarities to construct a hypothesis.

First, he narrows down fixing carbon to what may be the simplest and most ancestral pathway – the acetyl-CoA pathway – except that a simpler functional group could have initially substituted for CoA. Essentially he invokes the fundamental use of thioester chemistry in fixing CO2 and H2 into the bevy of organics required in a primitive biochemistry. He openly admits not knowing what this chemistry might look like in detail and he handwaves the formation of DNA (a gaping hole that may not be easy to solve given what we know from prebiotic syntheses). However, his picture is intriguing at the very least. The iron-sulfide cores of the hydrogenase and ferredoxin in methanogens suggest some continuity with the inorganic network that constitutes the hydrothermal vents.

LUCA may have started out lodged in the inorganic membrane between the acidic ocean and the alkaline hydrothermal liquid. The natural proton gradient results in an influx of protons from the acidic ocean into the cell. To maintain the influx requires relatively quick neutralization from the alkaline fluid, either by protons diffusing out the other side or from an influx of hydroxide. In any case, the membrane has to be leaky for this to work – this may be the case for simple fatty acids that are candidates for primitive cell membranes. (Many experiments suggest their synthesis is straightforward, and they allow for both growth and division of cell-like structures.) The problem is that LUCA is stuck where it is. Evolving a less permeable membrane kills the proton motive force to drive a primitive metabolism.

Lane thinks there might be an ingenious solution that kills two birds with one stone. The evolution of Na/H antiporters as a ‘preadaptation’ may have led to the further evolution of active pumping proteins, which would co-evolve with increasing membrane permeability. These could allow the cells increasing freedom from being stuck in the inorganic layer allowing them to ‘colonize’ other areas, be it in the vent system or possibly further afield. The bacteria and archaea may have come from two different evolutionary routes in this process. It may (in broad sweeping terms) explain the similarities and differences between the two domains of life. It certainly avoids some of the other problems that attempt to find the root to the tree of life (Lane enumerates the different possibilities, which he then argues against.)

The factoid that jumped out at me while reading this section was the amount of ‘waste’ generated compared to biomass synthesized. The ratio is 40 to 1. Methanogens spend most of their energy budget generating methane (and water) to pump protons. That’s the price to be paid in a free-living cell. In the leaky membrane of a cell attached to the wall of a hydrothermal vent, more energy may have been available in a natural proton gradient to drive a primitive (and evolving) carbon metabolism synthesizing the building blocks of proteins and nucleic acids. LUCA was a creature of the vent. Could we find LUCA now? Unfortunately not, as any other vent organisms now would devour metabolites and outcompete anything as primitive as LUCA. Could we build a LUCA under artificial conditions? Possibly. It won’t be easy, but it will be very interesting if some research group succeeds!

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