1. Genetic load (this post)
The genetic load argument has been around for 50 years. It's why experts did not expect a huge number of genes when the genome sequence was published. It's why the sequence of most of our genome must be irrelevant from an evolutionary perspective.
This argument does not rule out bulk DNA hypotheses but it does rule out all those functions that require specific sequences in order to confer biological function. This includes the speculation that most transcripts have a function and it includes the speculation that there's a vast amount of regulatory sequence in our genome. Chapter 5 of The Deeper Genome is all about the importance of regulatory RNAs.
So, starting from a failed attempt top turn a petunia purple, the discovery of RNA interference has revealed a whole new network of gene regulation mediated by RNAs and operating in parallel to the more established one of protein regulatory factors. ... Studies have revealed that a surprising 60 per cent of miRNAs turn out to be recycled introns, with the remainder being generated from the regions between genes. Yet these were parts of the genome formerly viewed as junk. Does this mean we need a reconsideration of this question? This is an issue we will discuss in Chapter 6, in particular with regard to the ENCODE project ...The implication here is that a substantial part of the genome is devoted to the production of regulatory RNAs. Presumably, the sequences of those RNAs are important. But this conflicts with the genetic load argument unless we're only talking about an insignificant fraction of the genome.
But that's only one part of Parrington's argument against junk DNA. Here's the summary from the last Chapter ("Conclusion") ...
As we've discussed in this book, a major part of the debate about the ENCODE findings has focused on the question of what proportion of the genome is functional. Given that the two sides of this debate use quite different criteria to assess functionality it is likely that it will be some time before we have a clearer idea about who is the most correct in this debate. Yet, in framing the debate in this quantitative way, there is a danger that we might lose sight of an exciting qualitative shift that has been taking place in biology over the past decade or so. So a previous emphasis on a linear flow of information, from DNA to RNA to protein through a genetic code, is now giving way to a much more complex picture in which multiple codes are superimposed on one another. Such a viewpoint sees the gene as more than just a protein-coding unit; instead it can equally be seen as an accumulation of chemical modifications in the DNA or its associated histones, a site for non-coding RNA synthesis, or a nexus in a 3D network. Moreover, since we now know that multiple sites in the genome outside the protein-coding regions can produce RNAs, and that even many pseudo-genes are turning out to be functional, the very question of what constitutes a gene is now being challenged. Or, as Ed Weiss at the University of Pennsylvania recently put it, 'the concept of a gene is shredding.' Such is the nature of the shift that now we face the challenge of not just recognizing the true scale of this complexity, but explaining how it all comes together to make a living, functioning, human being.I've already addressed some of the fuzzy thinking in this paragraph [The fuzzy thinking of John Parrington: The Central Dogma and The fuzzy thinking of John Parrington: pervasive transcription]. The point I want to make here is that Parrington's arguments for function in the genome require a great deal of sequence information. They all conflict with the genetic load argument.
Parrington doesn't cover the genetic load argument at all in his book. I don't know why since it seems very relevant. We could not survive as a species if the sequence of most of our genome was important for biological function.