Challenges facing the Origin of Life:
The Genetic Code
The Genetic Code
Given that current biological systems are based on the interdependence of proteins and nucleic acids then, whichever might have come first – or even something different - at some stage a link would need to have arisen between them. This link now requires many biochemical components - involved in DNA replication, transcription and translation - and at the heart of it is the genetic code: the way in which triplets of nucleotides (called codons) in DNA specify amino acids in the resulting proteins (Figure 1).
The origin of the genetic code is acknowledged to be a major hurdle in the origin of life, and I shall mention just one or two of the main problems. Calling it a ‘code’ can be misleading because of associating it with humanly invented codes which at their core usually involve some sort of pre-conceived algorithm; whereas the genetic code is implemented entirely mechanistically - through the action of biological macromolecules. This emphasises that, to have arisen naturally - e.g. through random mutation and natural selection - no forethought is allowed: all of the components would need to have arisen in an opportunistic manner.
Crucial role of the tRNA activating enzymes
To try to explain the source of the code various researchers have sought some sort of chemical affinity between amino acids and their corresponding codons. But this approach is misguided:
- First of all, the code is mediated by tRNAs which carry the anti-codon (in the mRNA) rather than the codon itself (in the DNA). So, if the code were based on affinities between amino acids and anti-codons, it implies that the process of translation via transcription cannot have arisen as a second stage or improvement on a simpler direct system - the complex two-step process would need to have arisen right from the start.
- Second, the amino acid has no role in identifying the tRNA or the codon . This association is done by an activating enzyme (see Figure 2) which attaches each amino acid to its appropriate tRNA (clearly requiring the enzyme to correctly identify both components). There are 20 different activating enzymes - one for each type of amino acid.
- Interestingly, the end of the tRNA to which the amino acid attaches has the same nucleotide sequence for all amino acids - which constitutes a third reason.
Interest in the genetic code tends to focus on the role of the tRNAs, but as just indicated that is only one half of implementing the code. Just as important as the codon-anticodon pairing (between mRNA and tRNA) is the ability of each activating enzyme to bring together an amino acid with its appropriate tRNA. It is evident that implementation of the code requires two sets of intermediary molecules: the tRNAs which interact with the ribosomes and recognise the appropriate codon on mRNA, and the activating enzymes which attach the right amino acid to its tRNA. This is the sort of complexity that pervades biological systems, and which poses such a formidable challenge to an evolutionary explanation for its origin. It would be improbable enough if the code were implemented by only the tRNAs which have 70 to 80 nucleotides; but the equally crucial and complementary role of the activating enzymes, which are hundreds of amino acids long, excludes any realistic possibility that this sort of arrangement could have arisen opportunistically.
Progressive development of the genetic code is not realistic
In view of the many components involved in implementing the genetic code, origin-of-life researchers have tried to see how it might have arisen in a gradual, evolutionary, manner. For example, it is usually suggested that to begin with the code applied to only a few amino acids, which then gradually increased in number. But this sort of scenario encounters all sorts of difficulties with something as fundamental as the genetic code.
- First, it would seem that the early codons need have used only two bases (which could code for up to 16 amino acids); but a subsequent change to three bases (to accommodate 20) would seriously disrupt the code. Recognising this difficulty, most researchers assume that the code used 3-base codons from the outset; which was remarkably fortuitous or implies some measure of foresight on the part of evolution (which, of course, is not allowed).
- Much more serious are the implications for proteins based on a severely limited set of amino acids. In particular, if the code was limited to only a few amino acids, then it must be presumed that early activating enzymes comprised only that limited set of amino acids, and yet had the necessary level of specificity for reliable implementation of the code. There is no evidence of this; and subsequent reorganization of the enzymes as they made use of newly available amino acids would require highly improbable changes in their configuration. Similar limitations would apply to the protein components of the ribosomes which have an equally essential role in translation.
- Further, tRNAs tend to have atypical bases which are synthesized in the usual way but subsequently modified. These modifications are carried out by enzymes, so these enzymes too would need to have started life based on a limited number of amino acids; or it has to be assumed that these modifications are later refinements - even though they appear to be necessary for reliable implementation of the code.
- Finally, what is going to motivate the addition of new amino acids to the genetic code? They would have little if any utility until incorporated into proteins - but that will not happen until they are included in the genetic code. So the new amino acids must be synthesised and somehow incorporated into useful proteins (by enzymes that lack them), and all of the necessary machinery for including them in the code (dedicated tRNAs and activating enzymes) put in place – and all done opportunistically! Totally incredible!
In view of these fundamental and insurmountable problems, it is no wonder that more than half a century after Miller’s first experiments, rather than solving the riddle of life’s origin, researchers have become far more aware of the difficulties. Yet the belief persists - or at least is promulgated - that life arose in a naturalistic way. It certainly seems that this view is based far more on commitment to a naturalistic ideology than on empirical science.
Notes display in the main text when the cursor is on the Note number.
1. This can be seen from an experiment in which the amino acid cysteine was bound to its appropriate tRNA in the normal way – using the relevant activating enzyme, and then it was chemically modified to alanine. When the altered aminoacyl-tRNA was used in an in vitro protein synthesizing system (including mRNA, ribosomes etc.), the resulting polypeptide contained alanine (instead of the usual cysteine) corresponding to wherever the codon UGU occurred in the mRNA. This clearly shows that it is the tRNA alone (with no role for the amino acid) with its appropriate anticodon that matches the codon on the mRNA.