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Thursday, July 06, 2023

James Shapiro doesn't like junk DNA

Shapiro doubles down on his claim that junk DNA doesn't exist.

It's been a while since we've heard from James Shaprio. You might recall that James A. Shapiro is a biochemistry/microbiology professor at the University of Chicago and the author of a book promoting natural genetic engineering. I reviewed his book and didn't like it very much—Shapiro didn't like my review [James Shapiro Never Learns] [James Shapiro Responds to My Review of His Book].

Shapiro has allied himself with Denis Noble and other founders of The Third Way—a group that challenges the modern view of evolution while distancing themselves from Young Earth Creationists [The Third Fourth? Way]. The only thing that unites this group is their opposition to a particular (mostly false) view of evolutionary theory. Shapiro claims credit for predicting that most of the human genome would be found to be functional and he was delighted when ENCODE seemed to vindicate his claim back in 2012 [James Shapiro Claims Credit for Predicting That Junk DNA Is Actually Part of a "highly sophisticated information storage organelle"]. His article in the Huffington Post was titled Bob Dylan, ENCODE and Evolutionary Theory: The Times They Are A-Changin' and it began with a quote from Bob Dylan, (WARNING! Turn off your irony meters.)

And don't criticize
What you can't understand

In 2021 Shapiro resurfaced with an article in the journal Biosemiotics where he and Denis Noble promoted their bizarre views on evolution. The two authors then combined to publish an article in Progress in Biophysics & Molecular Biology where they wondered why evolutionary biologists were not teaching the "truth" about genome evolution [More illusions/delusions of James Shapiro and Denis Noble]. His latest venture into windmill jousting is an article in aeon, Evolution without accidents, where he makes the case that there's more to evolution than just random mutations and natural selection (duh!).

The important part for me is the fact that he continues to dismiss junk DNA.

The ‘central dogma of molecular biology’, first enunciated by Francis Crick in 1958 and restated in 1970, assigned to RNA molecules the primary task of serving as intermediates carrying coding sequence data from the DNA to the ribosomes, where that data is translated into the sequence of amino acids in protein chains. According to this explanation, adaptation took place only through encoded proteins, and it became a puzzle to evolutionary biologists why the protein-coding sequences of the most complex organisms make up such a small fraction of their genomes. In our own genomes, for example, more than 50 per cent of the DNA does not code proteins (our genomes contain only about 1.5-2 per cent protein-coding DNA). This gave rise to notions that genomes contained large amounts of ‘junk’ DNA, which was simply reproducing itself in the name of its own ‘selfish’ survival, as popularised by Dawkins’s The Selfish Gene.

There are many things wrong with this paragraph but the most astonishing is Shapiro's continuing misrepresentation of the central dogma. He has been told repeatedly that this is NOT what Crick said in 1958 and 1970 but that hasn't sunk in [The illusions of James Shapiro]. It's interesting that he criticizes something that he can't understand. :-)

He's also confused about the difference between selfish DNA and Dawkins' view of the selfish gene [Selfish genes and transposons] but that's not surprising since history and accuracy are not Shapiro's strong points.

Notwithstanding the central dogma that proteins execute all the business of living cells, research in molecular genomics has revealed that all cells contain many noncoding RNA molecules (ncRNAs) and, by the late 2010s, the global Encyclopedia of DNA Elements project (ENCODE) found that human cells regulated expression of ncRNAs in the same ways as protein-coding mRNAs. In other words, ncRNAs are controlled and, presumably, biologically functional. They are not ‘junk’.

The ENCODE discoveries and subsequent research on ncRNAs have revolutionised our understanding of genome coding in two important ways. Firstly, many of the copies of TEs and other repeated DNA elements found in large complex genomes contribute transcription templates for the so-called ‘noncoding’ ncRNAs, which carry out a wide variety of cellular and developmental regulatory functions. Thus, there is no ‘selfish’ or ‘junk’ repetitive DNA in genomes; all regions of the human genome code for biologically significant molecules. Secondly, while the importance of ncRNAs was completely unexpected, it turns out that they influence all levels of organismal activity. These range from scaffolding the formation of multimolecular complexes in the cytoplasm, facilitating the formation of three-dimensional genome complexes in the nucleus, to stimulating the reprogramming of terminally differentiated tissue cells with limited growth potential into pluripotent stem cells. New functionalities for ncRNAs emerge daily, telling us that this class of molecules has enormous structural and functional diversity.

As Sandwalk readers know, there was never a time when knowledgeable scientists said that all noncoding was junk and never a time when the original proponents of junk DNA were unaware of noncoding genes. Thus, the discovery of ncRNAs is not new and does not refute junk.

Presumably what Shapiro really means to say is that 90% of our genome (including introns) consists of functional genes that specify ncRNAs. This is the revolution that he's talking about but it's a ridiculous claim. There is zero evidence to support such a claim.

I wonder if Shapiro has heard of the Onion Test?


Steve Watson said...

Heads up that Shapiro's got himself an article in Aeon:

Larry Moran said...


That's the article I'm discussing. It's online title is diffferent.

Arlin said...

The fallacy behind decades of radical claims from Shapiro (as with Denis Noble) is that, if some finding X in molecular genetics or comparative genomics (e.g., lateral gene transfer, CRISPR-Cas, whatever) departs from a standard 100-year-old Mendelian conception of alleles as beads on a string that rarely and independently micro-mutate to a different color, then the reality of X necessitates a new theory of evolution. That is just not how we roll, Dr. Shapiro. If you want to play evolutionary biologist, you have to do some evolutiony stuff. First, you develop a theory T for the evolutionary implications of X, and you use a formal model of T to demonstrate behavior that contradicts familiar expectations under old-fashioned Mendelism. Next, you get some results to back up T, showing that the contradictions are real and important for things we care about in evolutionary biology, like adaptation or speciation. Then, we can have a discussion about changing how we think.

Shapiro has been trying to do an end-run around evolutionary biology for his entire career. He is trying to appeal to those outside the discipline, without doing what evolutionary biologists do, which is to pursue evolutionary hypotheses.

Joe Felsenstein said...

Quite agree with Arlin. Shapiro argues not only that there is little or no junk DNA, but that the cell has a system for "natural genetic engineering". Sure, all sorts of bizarre types of genetic alterations occur. But he's saying more than that. He's arguing that the changes are responses to the needs of the cell by coming up with the very adaptations that are needed. Now all he needs to do is to show us where exactly in the cell is this marvelous teleological machinery. So far, nothing. Just lists of lots of strange genomic changes, and implications that these magically accomplish teleology, without any need for natural selection to sort among them.

John Harshman said...

When I was a grad student at U. of Chicago during the 1990s, in the Committee on Evolutionary Biology, during my entire career I never met or saw or even heard Shapior's name mentioned. I don't think he interacts much with evolutionary biologists. Or perhaps they just don't want to interact with him.

Anonymous said...

Joe, FYI, Shapiro isn't a very disciplined or sophisticated thinker when it comes to evolution. He uses provocative language without really understanding what he is saying. I suspect that his thesis is probably considerably more modest than it seems, something about applying agency to genomes via mutation, rather than applying consciousness. But like many people talking about mutation today, he doesn't know how to use his words to express ideas. The old language of random raw materials isn't suitable, and he can't be bothered to develop a new and philosophically coherent position, so he ends up saying things that trigger Darwin's homies without offering clear and sensible alternatives.

Anyway, as an expert on mutation and evolution, I read Shapiro so that other people don't have to. Ssee my 2 Shapiro-related answers on Quora:

Is Shapiro's "natural genetic engineering" a pseudoscience?

Does CRISPR validate James Shapiro's NGE theory?

Joe Felsenstein said...

@Arlin (aka "Anonymous" above: It would seem more appropriate to call a mutational event purposive if mutants that increase resistance to high temperatures occur more frequently when the temperature has risen than when the temperature has fallen. Just having it evolved so as to do not-so-bad on average does not sound to me warranted.

Arlin said...

@Joe, you're making my point for me. There are indeed cases where critical genes are targeted for mutation, or where mutations occur more often when they are beneficial. Evolved mutation strategies are real, e.g., V(D)J recombination and hypermutation in antibody maturation. Consider CRISPR-Cas spacer acquisition. Suppose phage pA is found in environment A, pB in B, and pC in C. The rate of mutation for acquiring a CRISPR-Cas defensive spacer against pA is highest in environment A where the selection coefficient s_A (for protection against pA) is also the highest. Same for pB in B and pC in C. This general pattern also applies to the acquisition of certain kinds of genes by lateral transfer, e.g., copper-resistance cassettes are more common in environments contaminated by copper, where they are also more beneficial, so they are more likely to be acquired by lateral-transfer mutations where they are beneficial.

This kind of automatic correlation between rate of mutation and beneficiality clearly contradicts statements that evo biologists have made for generations.

What do we call this? Old ways of thinking present us with dichotomies like "purposive" vs "random".

Shapiro confronts this situation and falls short, because he just suggests over and over again, vaguely, that mutation is purposive or intentional. That is not satisfactory.

However, falling back on the old trope that mutation is "random" is also not satisfactory.

Mikkel Rumraket Rasmussen said...

We call it random, but the increase in frequency is adaptive. An adaptive increase in frequency. Why is the old frequency random, but the new one not? What is the change in frequency when it changes from random to non-random?

What is it about the old frequency that made it the correct one to call random, and the new one be non-random? Is the old one not itself also likely to be in part a result of adaptation?

judmarc said...

@Arlin - Whenever people talk about genes being targeted for mutation, I always wonder how Lenski's E. coli got to be so dumb. Thousands upon thousands of generations, and only once has citrate metabolism evolved.