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Friday, July 24, 2015

John Parrington discusses pseudogenes and broken genes

We are discussing Five Things You Should Know if You Want to Participate in the Junk DNA Debate and how they are described in John Parrington's book The Deeper Genome: Why there is more to the human genome than meets the eye. This is the fourth of five posts.

1. Genetic load
John Parrington and the genetic load argument
2. C-Value paradox
John Parrington and the c-value paradox
3. Modern evolutionary theory
John Parrington and modern evolutionary theory
4. Pseudogenes and broken genes are junk (this post)
John Parrington discusses pseudogenes and broken genes
5. Most of the genome is not conserved
John Parrington discusses genome sequence conservation

4. Pseudogenes and broken genes are junk

Parrington discusses pseudogenes at several places in the book. For example, he mentions on page 72 that both Richard Dawkins and Ken Miller have used the existence of pseudogenes as an argument against intelligent design. But, as usual, he immediately alerts his readers to other possible explanations ...
However, using the uselessness of so much of the genome for such a purpose is also risky, for what if the so-called junk DNA turns out to have an important function, but one that hasn't yet been identified.
This is a really silly argument. We know what genes look like and we know what broken genes look like. There are about 20,000 former protein-coding pseudogenes in the human genome. Some of them arose recently following a gene duplication or insertion of a cDNA copy. Some of them are ancient and similar pseudogenes are found at the same locations in other species. They accumulate mutations at a rate consistent with neutral theory and random genetic drift. (This is a demonstrated fact.)

It's ridiculous to suggest that a significant proportion of those pseudogenes might have an unknown important function. That doesn't rule out a few exceptions but, as a general rule, if it looks like a broken gene and acts like a broken gene, then chances are pretty high that it's a broken gene.

As usual, Parrington doesn't address the big picture. Instead he resorts to the standard ploy of junk DNA proponents by emphasizing the exceptions. He devotes more that two full pages (pages 143-144) to evidence that some pseudogenes have acquired a secondary function.
The potential pitfalls of writing off elements in the genome as useless or parasitical has been demonstrated by a recent consideration of the role of pseudgogenes. ... recent studies are forcing a reappraisal of the functional role of these 'duds."
Do you think his readers understand that even if every single broken gene acquired a new function that would still only account for less than 2% of the genome?

There's a whole chapter dedicated to "The Jumping Genes" (Chapter 8). Parrington notes that 45% of our genome is composed of transposons (page 119). What are they doing in our genome? They could just be parasites (selfish DNA), which he equates with junk. However, Parrrington prefers the idea that they serve as sources of new regulatory elements and they are important in controlling responses to environmental pressures. They are also important in evolution.

As usual, there's no discussion about what fraction of the genome is functional in this way but the reader is left with the impression that most of that 45% may not be junk or parasites.

Most Sandwalk readers know that almost all of the transposon-related sequences are bits and pieces of transposons that haven't bee active for millions of years. They are pseudogenes. They look like broken transposon genes, they act like broken genes, and they evolve like broken transposons. It's safe to assume that's what they are. This is junk DNA and it makes up almost half of our genome.

John Parrington never mentions this nasty little fact. He leaves his readers with the impression that 45% of our genome consists of active transposons jumping around in our genome. I assume that this is what he believes to be true. He has not read the literature.

Chapter 9 is about epigenetics. (You knew it was coming, didn't you?) Apparently, epigentic changes can make the genome more amenable to transposition. This opens up possible functional roles for transposons.
As we've seen, stress may enhance transposition and, intriguingly, this seems to be linked to changes in the chromatin state of the genome, which permits repressed transposons to become active. It would be very interesting if such a mechanism constituted a way for the environment to make a lasting, genetic mark. This would be in line with recent suggestions that an important mechanism of evolution is 'genome resetting'—the periodic reorganization of the genome by newly mobile DNA elements, which establishes new genetic programs in embryo development. New evidence suggests that such a mechanism may be a key route whereby new species arise, and may have played an important role in the evolution of humans from apes. This is very different from the traditional view of evolution being driven by the gradual accumulation of mutations.
It was at this point, on page 139, that I realized I was dealing with a scientist who was in way over his head.

Parrington returns to this argument several times in his book. For example, in Chapter 10 ("Code, Non-code, Garbage, and Junk") he says ....
These sequences [transpsons] are assumed to be useless, and therefore their rate of mutation is taken to taken to represent a 'neutral' reference; however, as John Mattick and his colleague Marcel Dinger of the Garvan Institute have pointed out, a flaw in such reasoning is 'the questionable proposition that transposable elements, which provide the major source of evolutionary plasticity and novelty, are largely non-functional. In fact, as we saw in Chapter 8, there is increasing evidence that while transposons may start off as molecular parasites, they can also play a role in the creation of new regulatory elements, non-coding RNAs, and other such important functional components of the genome. It is this that has led John Stamatoyannopoulos to conclude that 'far from being an evolutionary dustbin, transposable elements appear to be active and lively members of the genomic regulatory community, deserving of the same level of scrutiny applied to other genic or regulatory features. In fact, the emerging role for transposition in creating new regulatory mechanisms in the genome challenges the very idea that we can divide the genome into 'useful' and 'junk' coomponents.
Keep in mind that active transposons represent only a tiny percentage of the human genome. About 50% of the genome consists of transposon flotsam and jetsam—bits and pieces of broken transposons. It looks like junk to me.

Why do all opponents of junk DNA argue this way without putting their cards on the table? Why don't they give us numbers? How much of the genome consists of transposon sequences that have a biological function? Is it 50%, 20%, 5%?


John Harshman said...

He also seems to be displaying the most common caricature of arguments for junk DNA: "We don't know what it's function is, therefore it's junk". Bet he can't find anyone actually making that claim, as opposed to using it as a strawman.

Jmac said...

"We don't know why some "related" species have preserved junk DNA while others didn't. We can't figure it out. We will trust that random and unintelligent processes must have known what they were doing. What choice do we have? We have to follow the argument that suits us and not where it leads. We are not creationists". - Expert Scientists in the Field


Piotr Gąsiorowski said...

To quote Joe Felsenstein's PG handbook (Chapter III.6: Mutational load; emphasis added):

If much of the DNA is simply “spacer” DNA whose sequence is irrelevant, then there will be a far smaller mutational load. But notice that the sequence must be truly irrelevant, not just of unknown function. If the “extra” DNA has regulatory or chromosome-pairing function requiring it to have a specific base sequence, then mutations in that sequence will still cause a mutational load, even if these loci are not producing polypeptide chains.

Anonymous said...

Septic Mind,

I think that if you actually tried to put together random words you wouldn't manage to be as incoherent as you are when you're serious.

But you're no layman, right you little idiot?

Anonymous said...

"almost all of the transposon-related sequences are bits and pieces of transposons that haven't been active for millions of years"

If "haven't been active" means not jumping around in the germline, then that is defensible.

But if "haven't been active" means having no regulatory role or not jumping around in somatic cells, that may not be as defensible.

Inactivity in the germline does not preclude activity in somatic cells which is still mostly unexplored. There is evidence in neuron cells of such activity and there likely will be more discovered in the future. Evidence suggests transposition in somatic cells may be important in differentiating somatic cells.

This paper touches on the TEs in somatic cells, including the neuron cells:

"The necessary junk: new functions for transposable elements" by
Alysson R. Muotri, Maria C.N. Marchetto, in Human Molecular Genetics

Furthermore, regulatory roles for transposon continue to be proposed such as having specific nucleosome binding properties, phasing of nucleosomes, serving as enhancers, epigenetic boundaries.

2007 paper in Nature by R. Keith Slotkin and Robert Martienssen describe the regulatory roles of Transposable elements.

So what fraction of the genome? Maybe we'll find out by actually looking and that means supporting the work of ENCODE and ROADMAP rather than relying on evolutionary theory to dictate what can and cannot be functional in the cell.

Aceofspades said...

What are you taking about? Which species have conserved junk DNA?

That sentence is contradictory since if a sequence is conserved then it is functional and it is not junk

John Harshman said...


Piotr Gąsiorowski said...

Merely pointing out that the mutational load argument definitely requires the presence of a lot of "true junk" as different from "DNA of unknown function" in a genome as big as ours, so conflating the two is indeed a caricature.

John Harshman said...

This is true for each of the arguments for junk, none of which has anything to do with "DNA of unknown function".

Mikkel Rumraket Rasmussen said...

For fucks sake, put some numbers on those fucking discoveries. What fraction of transposable elements have been discovered to have regulatory roles? I'm going to guess less that 1%.

You don't get anywhere by just bringing references that say some transposable element somewhere possibly has a regulatory function. You need to look at how many there are and how many have been shown to have a function. Why doesn't this sink in with you people? It's the same stupid shit every time.

Nullifidian said...

Aceofspades, I think SM possibly is not distinguishing between mere inheritance and conservation.