There's one post for each of the five issues that informed scientists need to address if they are going to write about the amount of junk in you genome. This is the last one.
1. Genetic load
5. Most of the genome is not conserved
There are several places in the book where Parrington address the issue of sequence conservation. The most detailed discussion is on pages 92-95 where he discusses the criticisms leveled by Dan Graur against ENCODE workers. Parrington notes that 9% of the human genome is conserved and recognizes that this is a strong argument for function. It implies that >90% of our genome is junk.
Here's how Parrington dismisses this argument ...
John Mattick and Marcel Dinger ... wrote an article for the HUGO Jounral, official journal of the Human Genome Organisation, entitled "The extent of functionality in the human genome." ... In response to the accusation that the apparent lack of sequence conservation of 90 per cent of the genome means that it has no function, Mattick and Dinger argued that regulatory elements and noncoding RNAs are much more relaxed in their link between structure and function, and therefore much harder to detect by standard measures of function. This could mean that 'conservation is relative', depending on the type of genomic structure being analyzed.In other words, a large part of our genome (~70%?) could be producing functional regulatory RNAs whose sequence is irrelevant to their biological function. Parrington then writes a full page on Mattick's idea that the genome is full of genes for regulatory RNAs.
The idea that 90% of our genome is not conserved deserves far more serious treatment. In the next chapter (Chapter 7), Parrington discusses the role of RNA in forming a "scaffold" to organize DNA in three dimensions. He notes that ...
That such RNAs, by virtue of their sequence but also their 3D shape, can bind DNA, RNA, and proteins, makes them ideal candidates for such a role.But if the genes for these RNAs make up a significant part of the genome then that means that some of their sequences are important for function. That has genetic load implications and also implications about conservation.
If it's not a "significant" fraction of the genome then Parrington should make that clear to his readers. He knows that 90% of our genome is not conserved, even between individuals (page 142), and he should know that this is consistent with genetic load arguments. However, almost all of his main arguments against junk DNA require that the extra DNA have a sequence-specific function. Those facts are not compatible. Here's how he justifies his position ...
Those proposing a higher figure [for functional DNA] believe that conservation is an imperfect measure of function for a number of reasons. One is that since many non-coding RNAs act as 3D structures, and because regulatory DNA elements are quite flexible in their sequence constraints, their easy detection by sequence conservation methods will be much more difficult than for protein-coding regions. Using such criteria, John Mattick and colleagues have come up with much higher figures for the amount of functionality in the genome. In addition, many epigenetic mechanisms that may be central for genome function will not be detectable through a DNA sequence comparison since they are mediated by chemical modifications of the DNA and its associated proteins that do not involve changes in DNA sequence. Finally, if genomes operate as 3D entities, then this may not be easily detectable in terms of sequence conservation.This book would have been much better if Parrington had put some numbers behind his speculations. How much of the genome is responsible for making functional non-coding RNAs and how much of that should be conserved in one way of another? How much of the genome is devoted to regulatory sequences and what kind of sequence conservation is required for functionality? How much of the genome is required for "epigenetic mechanisms" and how do they work if the DNA sequence is irrelevant?
You can't argue this way. More than 90% of our genomes is not conserved—not even between individuals. If a good bit of that DNA is, nevertheless, functional, then those functions must not have anything to do with the sequence of the genome at those specific sites. Thus, regions that specify non-coding RNAs, for example, must perform their function even though all the base pairs can be mutated. Same for regulatory sequences—the actual sequence of these regulatory sequences isn't conserved according to John Parrington. This requires a bit more explanation since it flies on the face of what we know about function and regulation.
Finally, if you are going to use bulk DNA arguments to get around the conflict then tell us how much of the genome you are attributing to formation of "3D entities." Is it 90%? 70%? 50%?