Chemistry Rules! (RJS)

Chemistry Rules! (RJS) December 6, 2018

Denis Alexander is a molecular biologist and it is to the molecular basis of life that he turns in Chapter 3 of his book “Is There Purpose in Biology?” As a chemist, I find this chapter fascinating. Biology is nothing without chemistry. To set the stage: in chapter 1 Denis introduced a historical perspective on the discussion of purpose in biology, in chapter 2 he outlined the Grand Narrative of biology. The increase in complexity in undeniable, from early single-cell organisms to the biodiversity that characterizes life today. The development of this biodiversity is characterized by convergence. Similar structures developed from very different directions. The eye provides one well known example of such convergence. Evolution is not a random process operating in a flat landscape. Rather there are physical constraints and optimal solutions.

There are chemical constraints as well. The cell is a complex bag of chemicals with proteins providing structure, transporting molecules, generating signals, sensing stimuli, and catalyzing critical chemical reactions. These proteins are composed of various arrangements of 20 common amino acids (although chemical modification can provide some additional variation exploited in the cell) along with various metals and other cofactors. The self-replicating DNA chains found in the chromosomes store the information that allows the production of the various proteins and other biological molecules required for life. Four nucleobases labeled A, C, T, and G are arranged in triplets code for the common amino acids. These are paired via hydrogen bonds in the well known double helix of DNA (Image credit).

Stephen Meyer (Signature in the Cell) suggested that the specificity of the DNA code was evidence for an intelligent designer. Denis does not refer directly to Meyer’s book, but offers a counterpoint to this argument. Although it is possible that the specific genetic code used by life on earth is a “frozen accident,” evidence is accumulating that this code has been shaped by chemical factors and preferences. There are clear patterns in the relationship of the triplets to the chemical properties of amino acids (their affinity for water, their size, and so forth).  A combination of stereochemical factors, error minimization, and coevolution may well have shaped the specific code we find.  The code was chemically optimized as it developed. Denis concludes:

But there appear to be good reasons why the code we now have appears to function so well in all living things today on planet Earth: physical and chemical constraints ensured that its generation was shaped by the needs of optimum functionality. If we find life on another planet, as seems very likely (and assuming we don’t contaminate it with Earthly molecules), it also seems a reasonable expectation that information-containing molecules like RNA and DNA will be present in its life-forms, and it would not be at all surprising to find a genetic code if not the same, at least similar, to the one we have on planet Earth. (p. 114)

Physico-chemical constraints also act on RNA – the transfer/messenger element that “reads” DNA and “writes” proteins and on proteins themselves. The chemistry is not random, but follows increasingly well understood patterns and rules. The specific amino acids are optimal for function – enabled by the way the proteins fold-up into three dimensional structures. Proteins with the same or similar functions in different species often have very similar structures or “folds” – even when the amino acid sequence differs substantially. Denis continues:

… it is that particular ensemble of folds that together specifies a protein’s function. Over the years, many classification schemes have been established and the three-dimensional structures of more than 100,000 proteins have now been published. The number of folds in all these proteins is estimated in the range 1,000-10,000. But even if the true number is 10,000, this is still a tiny number compared to 20100. In other words, all living things are united, not only by having the same genetic code, but also by possessing an elegant and highly restricted set of protein structures. Only this particular set, presumably, will carry out all the various functions that are required for proteins to organize the biochemical processes of life. (p. 119)

Proteins, especially enzymes, provide another example of evolutionary convergence. Similar mutations at specific locations have occurred multiple times in response to external stimuli. Denis writes: “Convergent evolution also applies just as much to proteins as to other components of living things. … The specific amino acid sequences of proteins that bestow upon them specific enzymatic activities is no accident This again contrasts sharply with what biologists initially thought would be the case before structural studies began.” (p. 121) Several examples are outlined  … echolocation, photosynthesis, chirpless crickets, and viral resistance in insects among others. (Read the book – Denis gives a highly readable summary.) The bottom line is that evolution converts randomness into purpose, and a common selective agent (say viral threat) can lead to the same common solution at different times and places. Chemistry constrains the possible, the efficient, and the effective.

More broadly, the observations on the sophisticated structure of the genetic code; the elegant selection of a limited repertoire of protein structures out of possible field of trillions; the “arrival of the frequent” due to the physical constraints on the structure of molecules such as RNA so that the material “presented” to natural selection is already heavily preselected and far from merely random; the way in which genomic systems are set up to facilitate evolvability; and the ubiquitous phenomena of convergence – all these facets of the molecules that make life possible point to a high degree of organization and constraint in which molecular mechanisms are “steered” along certain channels defined by the needs and challenges of being alive (and reproducing) on planet Earth. All this does render somewhat implausible the claim that the molecular systems involved, taken in their entirety, are necessarily Purposeless. (p. 139)

This isn’t an argument for a designer … rather it is an argument against unrestrained randomness and chance. The chemistry that permits and powers life is highly constrained by a wide range of factors. It is simply not true that life is a random and lucky accident, or that many other forms of life are equally likely. Using atoms arranged into molecules, there are only so many ways to achieve the necessary functions for life. Biochemistry/molecular biology reveals an elegant and coherent chemical story we are only beginning to understand.

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