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Thursday, October 18, 2018

The role of chance in evolution

I highly recommend this brief editorial by Naruya Saitou: "Chance, Finiteness, and History" (Saitou, 2018). Saitou is a strong proponent of Neutral Theory and the importance of random genetic drift. Together these influences, along with the "random" nature of mutation, introduce a major element of chance and accident into evolution.

Saitou was a student of Masatochi Nei and he recounts how he was influenced by Nei's 1987 book "Molecular Evolutionary Genetics." I remember reading that book 30 years ago and being very impressed with Nei's case for mutationism. Dan Graur also studied with Nei and he was kind enough to introduce me to Nei a few years ago in Chicago.

I think it's very clear that the role of chance in evolution, especially in molecular evolution, is very much underappreciated by the average scientist and by almost all non-scientists who are interested in the field. I doubt they will be convinced by a short essay but at least it will alert them to a different way of thinking.

Here's an example from Saitou's essay of that way of thinking ...
This world is finite. Our earth is just a 40,000-km circumference sphere. Life evolved on this tiny planet. We have to face the finiteness of the living world when we think about evolution. Random fluctuation of DNA copies (allele frequencies in classic sense) is a logical consequence of this finiteness. Because evolution follows time, evolution is historical. And chance played an important role in evolutionary history, as already noted by Darwin (1859). This is why I often mention three words—chance, finiteness, and history—in my talks and books as well as the title for this perspective.
Saitou is using "evolution" in two different senses. First, there's the ongoing process involving changes in allele frequencies and then there's the history of life. I think it's best to avoid using the word "evolution" as a stand-in for the history of life but that's just a quibble. The idea behind the history of life is that the pathway that each extant lineage has followed over the past three billion years is very much due to chance and accident. It's like Gould's idea that the tape of life can't be replayed.

The essay contains a sentence about junk DNA ...
From direct comparison of protein or RNA coding gene regions with noncoding regions of many genomes, it became clear that the majority of intergenic regions and introns are in fact “junk” DNA, as predicted by Ohno (1972).
This is about all the comment that's needed if you're a population geneticist. From their perspective, the debate is over and junk DNA won decisively over the speculation that most of our genome is functional. I wish more scientists, journalists, and philosophers would realize that the leading experts have reached a consensus on this subject.1

1. Let me repeat what I've said many times before: you don't have to agree with the views of these experts but you do have to acknowledge what you are up against when you argue for function. Do not mislead your audience by ignoring the experts in order to make your own opinion seem more reasonable.

Saitou, N. (2018) Chance, finiteness, and history. Molecular Biology and Evolution, 35(6), 1556-1557. [doi: 10.1093/molbev/msy087]

Tuesday, October 16, 2018

John Mattick's latest attack on junk DNA

John Mattick is the most prominent defender of the idea that the human genome is full of functional sequences. In fact, he is just about the only scientist of any prominence who's on that side of the debate. His main "evidence" is the fact that genomes are pervasively transcribed and that most of the transcripts are functional. Let's look at his latest review paper to see how well this argument stands up to close scrutiny (Mattick, 2018).1

As you read this post, keep in mind that in 2012 John Mattick was awarded a prize by the Human Genome Organization for proving his hypothesis [John Mattick Wins Chen Award for Distinguished Academic Achievement in Human Genetic and Genomic Research].
The Award Reviewing Committee commented that Professor Mattick’s “work on long non-coding RNA has dramatically changed our concept of 95% of our genome”, and that he has been a “true visionary in his field; he has demonstrated an extraordinary degree of perseverance and ingenuity in gradually proving his hypothesis over the course of 18 years.”
Mattick follows his usual format by giving us his version of history. He has argued for the past 15 years that the scientific community has been reluctant to accept the evidence of massive amounts of regulatory RNA genes because it conflicts with the standard paradigm of the supremacy of proteins. In the past he has claimed that this paradigm is based on the Central Dogma which states, according to him, that the only real function of DNA is to make proteins [How Much Junk in the Human Genome?]. As we shall see, he hasn't abandoned that argument but at least he no longer refers to the Central Dogma for support

Saturday, October 13, 2018

The great junk DNA debate

I've been talking to philosophers lately about the true state of the junk DNA controversy. I imagine what it would be like to stage a great debate on the topic. It's easy to come up with names for the pro-junk side; Dan Graur, Ford Doolittle, Sean Eddy, Ryan Gregory etc. It's hard to think of any experts who could defend the idea that most of our genome is functional. The only scientist I can think of who would accept such a challenge is John Mattick but let's imagine that he could find three others to join him in the great debate.

I claim that the debate would be a rout for the pro-junk side. The data and the theories are all on the side of those who would argue that 90% of our genome is junk. I don't think the functionalists could possibly defend the idea that most of our genome is functional. What do you think?

Assuming that I'm right, why is it that the average scientist doesn't know this? Why do they still believe there's a good case for function when none of the arguments stand up to close scrutiny? And why are philosophers not conveying the true state of the controversy to their readers? I'm told that anti-junk philosophers like Evelyn Fox Keller are held in high regard even though her arguments are easy to refute [When philosophers talk about genomes]. I'm told that John Mattick is highly respected in philosophy circles even though knowledgeable scientists have little use for his writings.

Can readers help me identify papers by philosophers of science that come down on the side of junk DNA and conclude that experts like Graur, Doolittle, etc are almost certainly correct?

Image Credit: The cartoon is by Tom Gauld and it was published online at the The New York Times Magazine website. I hope they will consider it fair use on an educational blog. See: Junk DNA comments in the New York Times Magazine.

Tuesday, October 09, 2018

Alternative splicing and the gene concept

I just learned about a workshop scheduled for the end of this month. The topic is: Evolutionary Roles of Transposable Elements and Non-coding DNA: The Science and the Philosophy.

I'd love to attend but it's a just small workshop designed to encourage dialogue between scientists and philosophers who are interested in the topic. Here's a list of the speakers ...
  • Ryan Gregory: Junk DNA, genome size, and the onion test.
  • Stefan Linquist: Four decades debating junk DNA and the Phenotype Paradigm is (somehow) alive and well.
  • Chris Ponting: 92.9% of the human genome evolved neutrally.
  • Paul Griffiths: Both adaptation and adaptivity are relevant to diagnosing function.
  • Ford Doolittle: Selfish genes and selfish DNA: is there a difference?
  • Justin Garson: Biological functions, the liberality problem, and transposable elements.
  • Joyce Havstad: Evolutionary Thinking about Critique of Function Talk.
  • Guillame Bourque: Impact of transposable elements on human gene regulatory networks.
  • Ulrich Stegman: On parity, genetic causation and coding.
  • Steven Downes: Understanding non-coding variants as disease risk alleles.
  • Alexander Palazzo: How nuclear retention and cytoplasmic export of RNAs reduces the deleteriousness of junk DNA.
  • David Haig: Pax somatica
  • Cedric Feschotte: Transposable elements as catalysts of genome evolution.