Evolution under the microscope

The Origin of Life: Some Blind Alleys

In a short article such as this I cannot deal fully with the various possibilities that have been pursued to try to circumvent the formidable challenges facing the origin of life. But I will give an indication of the fundamental difficulties, and expose some key flaws and uncritical even wishful thinking in putative scenarios – which, unfortunately, are usually completely overlooked in popular accounts of the origin of life.

Abiotic origin of monomers – but what’s needed are polymers

First it must be emphasised that producing monomers – amino acids or the bases found in nucleic acids (DNA and RNA) – in prebiotic soup experiments, so often portrayed as proof that life could have arisen naturally, is nothing of the sort. Because what is needed are polymers of these; and not just any polymer, but those with a sequence that confers useful biological activity; and in the context of the origin of life, that activity needs to be self-replicating, or at least contributing to a replicating system.

Yet the formation of polymers in itself (regardless of the possible usefulness of their sequence) presents several problems which for the sake of clarity I shall discuss first in the context of amino acids and proteins, and comment later on the applicability of these comments to nucleotides and nucleic acids.

  1. The most basic problem is that the amino acids must be able to join together, by linking the carboxyl group of one amino acid to the amino group of the next to form what is called a peptide bond (Figure 1). But this is a condensation reaction (involving loss of water) so it will not occur readily in an aqueous environment (such as a primeval soup); and it is significantly endothermic (energetically unfavourable), so it will not occur at all without the input of energy. This is why in the cell (a) ribosomes limit access of water to the active site where peptide bonds are formed [1], and (b) peptide bond formation is linked to the breaking of high-energy phosphate bonds so that the energy released in the latter can be used to enable the former. [2]
peptide bond

Figure 1. Formation of a peptide bond.

  1. But forming the peptide bonds is only half of the problem. Because any scenario to try to generate biologically active proteins would require a plentiful supply of amino acids (not the meagre yield found in soup experiments) and some means of trying out different amino acid sequences (to try to find one with biological activity). That is, there needs to be means for breaking peptide bonds, to separate the amino acids, and then recombining them in a different sequence.
  2. Abiotically, it requires many hours in hot mineral acid to hydrolyse peptide bonds (which is why proteins are so stable, and suitable for building biological tissues), but biologically this reaction is achieved readily with appropriate enzymes (e.g. the digestive enzyme trypsin).

    So the point I am making here is that the conditions required to make and break peptide bonds are very different. That is, prebiotic scenarios would require transfer of the nascent polypeptides from one sort of environment to a chemically very different one, or some means of radically changing the conditions in the same environment (but without flushing out the polypeptides).

    Whilst it is not too difficult to envisage possible situations (e.g. using ocean vents) that might have given the required different or changing conditions, at the very least this means that the volume where such ‘experiments’ might have taken place would have been severely limited – we certainly cannot envisage oceans of productive primeval soup.

    As indicated here, a simple calculation shows that even with a virtually unlimited supply of amino acids and enzymatic production of proteins, the odds of producing a biologically active protein are practically hopeless. So how much more hopeless is the situation where prebiotic conditions are taken into account?

  3. Finally, in the discussion so far I assumed that only the desired peptide bond formation (i.e. between the carboxyl group of one amino acid with the amino group of the next) would take place under abiotic conditions. However, origin-of-life researchers are well aware that this is anything but the case: in reality, all sorts of undesired chemical reactions take place as well – mostly resulting in an ill-defined tar, rather than a polypeptide. Biologically, of course, enzymes ensure that only the desired peptide bond formation takes place.

So the few points mentioned above illustrate how a little thought readily exposes fatal flaws in the simplistic origin-of-life scenarios which are so often advanced in evolutionary texts.

RNA World?

Interest in the possible role of RNA as the earliest macromolecules arose in the 1980s when it was realised that RNA not only has an information-mediating role within cells (e.g. as mRNA and tRNA), but is also involved in carrying out catalytic functions. For example, RNA comprises about 60% of ribosomes and evidence emerged indicating that the RNA has a primary role in the synthesis of peptide bonds. (This is an intriguing facet of the chicken-and-egg relationship of proteins and nucleic acids, with each actually synthesizing the other.)

However, just as there are severe problems with an abiotic origin of polypeptides, similar issues apply to the production of polynucleotides, except that chemical considerations make the situation even worse.

ribonucleotide

Figure 2. Example of a ribonucleotide – guanosine monophosphate

This is because the nucleotides themselves each comprise a base, sugar, and phosphate (Figure 2) which need to be joined together correctly – involving two endothermic condensation reactions (with all the problems that means) to make a nucleotide in addition to the endothermic condensation reaction involved in joining the nucleotides. In other words, compared with polypeptides, nucleotides are even harder to synthesise and easier to destroy; in fact, to date, there are no reports of nucleotides arising from inorganic compounds in primeval soup experiments.

The other extremely important issue is of course that, just as a polypeptide must be long enough and have the right sequence to be able to fold and have a useful biological function, the same is true of RNA.

Which brings us back to the key problem facing the origin of life: how did the information content of the protein and RNA sequences arise? Popular views would have us believe that it was through random production and association of amino acids and/or nucleotides; but we have seen that such an explanation is totally untenable.

Starting with a poor replicator doesn’t work

It is of course widely recognised that even basic replication systems as we know them are complex and could not possibly have arisen spontaneously. And the response to this is to assume (uncritically) that life could have got started with much simpler systems e.g. with short polymers which gradually improved their activity through the action of natural selection.

But there are some fundamental objections to this sort of scenario.

  1. First, as mentioned elsewhere, a protein must be able to fold, into a specific 3-dimensional shape in order to have biological activity. But the forces holding the folded protein in shape are so weak that many amino acids need to be involved – imposing a minimum length on their sequence of about 70 [3], and maybe 50 for nucleic acids. So trying to improve the odds of finding a biologically active macromolecule by starting with short ones, just will not work.
  2. A similar misperception is that the first replicator need only have had poor replicating ability, which could gradually have improved (by mutation and selection of improved versions). But it is important to note that a poor replicator is more likely to degrade through miscopying than to improve its performance, and this poses a dilemma for the production of a primitive replicator. Although the common presumption is that a crude replicator can gradually improve its performance through a natural selection sort of process, in fact there is a threshold before that could take place. That is, a replicator must already have a reasonably good performance in order to be able to improve on that performance.
  3. In other words, natural selection cannot take place until there is a reasonably reliable replicating system.

    So the first replicating system would need to have arisen exclusively by chance.

 


Notes

Notes display in the main text when the cursor is on the Note number.

1. Rodnina M, Beringer M, and Wintermeyer W. ‘How ribosomes make peptide bonds’, TRENDS in Biochemical Sciences, 32(1), 20-26 (2007).

2. The formation of each peptide bond is powered by 4 high-energy phosphate bonds. See Wikipedia article ‘Translation_(biology)’, accessed on 25/1/2017.

3. Kyte J, Structure in protein chemistry, Garland Publishing, 1995, p243.