Challenges facing the Origin of Life:
Multiple layers of complexity
The complexity of life
We have come to realise that even the simplest forms of life are complex on at least two different levels.
1. The interdependence of biological macromolecules
First, life depends on the interdependence of many different biological macromolecules, typified by the replication of DNA and the synthesis of proteins.
- Despite the conceptual simplicity with which double stranded DNA can duplicate – each strand acting as a template to build the other – DNA cannot copy itself, but requires many proteins (mostly enzymes, but also others) to carry out the process (Figure 1). (A summary of the process can be found in textbooks of molecular biology, or at many sites on the internet, such as http://en.wikipedia.org/wiki/DNA_replication .)
- But neither can proteins replicate themselves: that requires DNA to specify the sequences of amino acids in the proteins, and various RNAs (also coded by DNA) that are part of the molecular machinery used to implement the genetic code (Figure 2). The major types of RNA are messenger RNA (mRNA) which carries a copy of the relevant gene; transfer RNA (tRNA) which mediates the genetic code; and ribosomal RNA (rRNA) which is a key component of ribosomes where the protein synthesis actually takes place. (A summary of protein synthesis can be found at http://en.wikipedia.org/wiki/Protein_biosynthesis .)
As Karl Popper said,
What makes the origin of life and the genetic code a disturbing riddle is this: the code cannot be translated except by using certain products of its translation. 
And there is an intriguing twist to this: not only are proteins and nucleic acids necessarily involved in biosynthesis of the other, each actually synthesises the other. It’s not surprising that nucleic acids (both DNA and RNA) are synthesised by protein enzymes; but what was surprising was to find that, although ribosomes (where proteins are synthesised) comprise both proteins and RNA, the chemical groups actually involved in catalysing formation of peptide bonds are exclusively part of the RNA. 
2. The individual macromolecules are complex
Importantly, the complex interaction of biological macromolecules is only one aspect of the problem facing the origin of life. What compounds the enigma is that the individual macromolecular components are themselves complex, in the sense that their sequences – of ribonucleotides in the case of RNA, or amino acids for proteins – are very specific.
The linear amino acid sequence of a protein is specific because it must (a) be able to fold into a discrete 3-dimensional structure, and (b) have the right amino acids in the right positions in the linear sequence so that, when folded, they are in exactly the right positions in relation to each other to form the active site(s) of the protein.
For more on this see proteins need to fold.
(And similar considerations apply to RNAs.)
Sequences that meet these criteria are exceedingly rare compared with the astronomical number of possible sequences of a suitable length. For example Douglas Axe has estimated that only 1 in about 1074 possible sequences will have biological function . So it is totally unrealistic to think that such sequences could have arisen by chance. How much less a suite of mutually dependent macromolecules?
If the components themselves were not so improbable then it might be realistic to think that a complex combination of components could arise by chance; but the extreme improbability of the individual components is such that they are very unlikely to arise individually, and hence there is no chance whatever of an interdependent system.
Where even just two macromolecules are required to perform a function, then it would be necessary for both components to arise together: Because natural selection does not have foresight: if one component arises alone it will not be retained for potential future usefulness (when the second component is available), but will almost certainly degrade by mutation. And, it should be noted, if the probability of getting one component is 1 in 1074 then the probability of getting two together is 1 in 10148 (not 1 in 2 x 1074); and so on for multi-component systems. This is why the obligatory mutual dependence of many macromolecules in even basic biological systems completely defies any hope of an evolutionary origin.
In summary, the crux of the problem is that even a basic biological replicating system requires (a) several macromolecules with complementary functions with (b) each having a highly improbable sequence. And this combination of complexities presents an insurmountable challenge to a naturalistic origin of life.
Notes display in the main text when the cursor is on the Note number.
1. Popper K R, Scientific reduction and the essential incompleteness of all science, Chapter 16 in Studies in the philosophy of biology, Eds Ayala and Dobzhansky, University of California Press, 1974.
2. Rodnina M, Beringer M, and Wintermeyer W. ‘How ribosomes make peptide bonds’, TRENDS in Biochemical Sciences, 32(1), 20-26 (2007).
3. Axe D, Estimating the prevalence of protein sequences adopting functional enzyme folds, in J. Mol. Biol., 2004 Aug 27; 341(5):1295-315.
4. Image from http://www.wehi.edu.au/wehi-tv/molecular-visualisations-dna