Saturday, November 24, 2012

55. Dyson's Proteins-First Model for the Origins of Life

In 1985 Freeman John Dyson wrote a little book Origins of Life, in which he argued that metabolic reproduction and replication are logically separable propositions, and that natural selection does not require replication, at least for simple creatures. In higher-level life as seen today, reproduction of cells and replication of molecules occur together. But there is no reason to presume that this was always the case. According to Dyson, it is more likely that life originated twice, with two separate kinds of organisms, one capable of metabolism without exact replication, and the other capable of replication without metabolism. At some stage the two features came together. When replication and metabolism occurred in the same creature, natural selection as an agent for novelty became more vigorous.

Eigen and Orgel had demonstrated (cf. Part 53), by two different experiments (one involving templates and the other involving enzymes), that a solution of nucleotide monomers can, under suitable conditions in the laboratory, give rise to a nucleic-acid polymer molecule (RNA) which replicates and mutates and competes with its progeny for survival. Living cells use both templates and enzymes for making RNA. This work pointed to a possible parasitic development of RNA-based life in an environment created by a pre-existing protein-based life.

During millions of years of chemical (and later also biological) evolution, the initial primitive but living cells diversified and refined their metabolic reaction pathways. In particular, they evolved the synthesis of ATP (adenosine triphosphate) through some autocatalytic reaction mechanisms (cf. Part 46). ATP is the main energy-carrying molecule in all present-day cells. ATP-carrying primitive cells had an evolutionary advantage over other, less efficient, cells. In time, other molecules like AMP (adenosine monophosphate) emerged; or perhaps AMP came first, and then ATP.

Although ATP and AMP have similar chemical structures; they play totally different roles in present-day cells. ATP is the universal biological currency for energy. AMP, on the other hand, is one of the nucleotides in the structure of the RNA molecule.

If ATP loses two of its three phosphate groups, it becomes AMP. Dyson argued that, although the primitive cells had no genetic apparatus to begin with, they were loaded with ATP molecules which could easily convert to AMP molecules. Accidentally, in one such cell which happened to be carrying AMP and other nucleotides (the ‘chemical cousins’ of AMP), the Eigen experiment for synthesizing RNA happened spontaneously. With some help from pre-existing enzymes, an RNA molecule got produced. Once created, it went on replicating itself because of the proclivity of base A to hydrogen-bond with base U, and of G to hydrogen-bond with C.

Thus, RNA first appeared as a parasitic disease in the cell. Although most such cells died of disease, some evolved to survive the infection, à la Lynn Margulis (cf. Part 51). In such cells, the parasite gradually became a symbiont. Further evolution resulted in a situation in which the protein-based life learnt to make use of the ability for exact replication provided by the chemical structure of RNA.

Is it really true that proteins emerged before RNA? The early evidence came from laboratory experiments done during the 1950s. The well-known experiments by Miller and others (cf. Part 53) demonstrated that amino acids form easily in a reducing atmosphere from the still simpler molecules, in the presence of ultraviolet radiation.  What about nucleotides?

They are more difficult to synthesize. A nucleotide has three parts: an organic base, a sugar, and a phosphate ion. The phosphate ion occurs naturally as a constituent of rocks and sea water.  The sugar (ribose) part can be synthesized with substantial efficiency from formaldehyde. And the synthesis of an organic base was demonstrated by Oró in 1960. He prepared a concentrated solution of ammonium cyanide in water, and just let it stand. Adenine was self-created, with a 0.5% yield. Guanine also got synthesized in a similar way. But the catch here is that it is difficult to imagine how such high degrees of concentration of ammonium cyanide could occur in Nature, although some possible scenarios have been suggested.

Dyson has given an updated version of his earlier ideas, in the book Life: What a Concept!(2008). In his updated model there are six stages in the evolution of chemical complexity, leading to the emergence of life.

Stage 1. The early cells were just little bags of some kind of cell membrane (as I have described in the lipid-first model in Part 54). This is the ‘garbage bag model’ for Stage 1. And inside the bag there was a more or less random collection of organic molecules, with the characteristic that small molecules could diffuse in through the vesicle membrane, but big molecules, once synthesized, could not diffuse out. Thus the ‘garbage bag’ situation was conducive to the conversion and retention of small molecules into large molecules. The higher concentration of organic material in the bag led to a higher efficiency of the chemical processes involved.

This evolution did not involve any replication processes. ‘When a cell became so big that it got cut in half, or shaken in half, by some rainstorm or environmental disturbance, it would then produce two cells which would be its daughters, which would inherit, more or less, but only statistically, the chemical machinery inside.’

Stage 2. Parasitic RNA appeared in some of the cells in Stage 2. ATP had appeared in one of the garbage bags by a random process in Stage 1, and the cell hosting it had a metabolic advantage over other cells. Therefore many cells with large amounts of ATP got created. Then, again by chance, ATP changed to AMP in one of the cells. In due course, AMP and its chemical cousins polymerized into a primitive form of RNA. Thus there was parasitic RNA inside these cells, forming a separate form of life, which was pure replication without metabolism. To quote Dyson: ‘Then the RNA invented viruses. RNA found a way to package itself in a little piece of cell membrane, and travel around freely and independently. Stage two of life has the garbage bags still unorganized and chemically random, but with RNA zooming around in little packages we call viruses carrying genetic information from one cell to another. That is my version of the RNA world’.

Stage 3. This stage started when the protein and the RNA systems started to collaborate. This happened after the emergence of the ribosome. Although this arrangement had the rudiments of the modern cell, the genetic information was shared mostly via viruses travelling from cell to cell. This was some kind of open-source heredity. The chemical inventions made by one cell could be shared with others. Evolution went on in parallel in many different cells. The best chemical devices could be shared between different cells and combined, so the chemical evolution was very rapid, as it occurred in parallel by many pathways.

Stage 4. Speciation and sex appeared in Stage 4, and that marked the beginning of the Darwinian era, when species appeared. ‘Some cells decided it was advantageous to keep their intellectual property private, to have sex only with themselves or with the members of their own species, thereby defining species. That was then the state of life for the next two billion years, the Archeozoic and Proterozoic eras. It was a rather stagnant phase of life, continued for two billion years without evolving fast.’

Stage 5. Multicellular organisms appeared in Stage 5, which also involved death.

Stage 6. This is the stage when we humans appeared.