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Saturday, May 20, 2017

Denis Noble writes about junk DNA

I have read Dance to the Tune of Life. It's a very confusing book for several reasons. Denis Noble has a very different perspective on evolution and what evolutionary theory needs to accomplish. He thinks that life is characterized by something he calls "Biological Relativity." I don't disagree. He also thinks that evolutionary theory needs to incorporate everything that has ever happened in the history of life. That's where we part company.

I'm working slowly on a book about genomes and junk DNA so I was anxious to see how Noble deals with that subject. I tend to judge the quality of books and articles by the way they interpret the controversy over junk DNA. Here's the first mention of junk DNA from page 89. He begins by saying that it's difficult to explain development and the diversity of tissues in multicellular organisms. He continues with,
Not only is that diversity difficult to explain. The diversity amongst different species is also still difficult to explain. We humans share nearly all our genome with that of a mouse. With just a few differences, virtually all the same proteins are made using the same germline genome templates. That is even more true when comparing us with a monkey species. And even comparing humans with a simple worm, like C. elegans, we find that we have similar number of 'genes' (as protein templates), which is between 20,000 and 25,000. There are plants that have more 'genes' than we do. It could be that many of the important factors responsible for the differences lie in the regions of the genome that were once once labeled as 'junk'—meaning without function—which accounts for more than 95% of the human genome. That idea of 'junk' DNA has now itself been junked as we have found that the great majority of the sequences are transcribed into RNAs. Many RNAs have function within the organism, for example in controlling the genome, and some of them are also inherited independently of DNA. This takes us into areas of modern biological science that are at the very frontier of current research. Epigenetic control of the genome will be discussed in chapter 8.
This is a remarkable passage for several reasons. It's surprising to me that after all the discoveries of the 1980s Noble still doesn't understand the basic principles of developmental biology. I think I have a pretty good idea why whales and humans look so different in spite of the fact they have similar genes. It's because of differences in the expression of those genes during development. I don't find that difficult to explain. We don't need to look for extraordinary explanations when transcription factors and regulatory sequences—known since the 1960s—are quite capable of creating diversity.

I'm also surprised that after all the public controversy over ENCODE and junk DNA, he still thinks that pervasive transcription rules out junk DNA. If he actually believes that most of our genome makes important regulatory RNAs then that's a real problem for the definition of 'gene' that he discusses at numerous points in the book. In several passages he attacks the traditional molecular definition of "gene," which he thinks is equivalent to "protein-coding DNA."1

The only other place where junk DNA comes up is on pages 228-229. He seems to acknowledge that there's more to evolution than traditional genes. Clearly ENCODE leaders must have known this. But that doesn't Denis Noble from criticizing his whipping-boy version of gene-centric evolution.
Isn't a Lot of DNA 'Selfish', 'Parasitic'?

One of the standard defenses of selfish gene theory is based on the discovery that, in humans and many other organisms, only a few percent the genome codes for proteins and can therefore be classified as 'genes' in the original molecular biological sense. The rest was described as 'junk' DNA, the ultimate example of 'selfishness' since it was seen as DNA 'hitching a ride' with no function, a bit like a virus that has become permanently resident in the body. The strong implication is that this discovery favors the selfish gene view.
In order to understand this passage, you need to know a bit about Denis Noble's view of evolution. He thinks modern evolutionary theory is based on The Selfish Gene by Richard Dawkins. He also thinks Dawkins was referring to real genes rather than metaphorical genes. That's the same kind of misunderstanding that I discussed in covering the Lu and Bourrat paper. There seems to be a widespread belief out there—a belief shared by both philosophers and biologists—that evolutionary theory is based solely on natural selection acting on traditional genes.

Noble shares another widespread misconception concerning junk DNA. He thinks the problem of junk DNA was solved in 1980 when a series of paper appeared in Nature. Those papers tried to account for extra DNA by suggesting that it was selfish DNA consisting mostly of transposons and viral DNA. These people think that the problem of excess DNA was incorporated into, and fully explained by, selfish gene theory.

The truth is very different. Less than 1% of the excess DNA in our genome consists of functional transposons and viruses.2 You can't explain junk DNA by pretending that it's selfish in the sense used by Dawkins or the authors of those Nature papers. 90% of our genome is real junk that's not "selfish" at all by any definition of the word.

Noble's view leads to confusion on many levels.
We now know that it's a confusing way of viewing genomes. There are several ways in which the confusion can be unraveled.

The words selfish junk etc. are, of course, metaphors. More importantly they are empirically empty metaphors when applied to sequences of DNA. No conceivable experiment could validate or invalidate them, as explained in chapter 5. That the metaphors are empty from the standpoint of empirical science does not mean they have no impact. On the contrary, they have had, and still have, very persuasive impact on the way in which many people think about biology.
If certain DNA sequences are junk then the best way to prove this is to remove them and see what effect they have on the organism and the population. Some of those experiments have been done. There are other ways of gathering evidence for function or for junk. It is not true that the claim of abundant junk DNA is immune to scientific investigation. That's a very strange statement.

It's true that you can think of "junk" and "selfish" as metaphors. But these words also have real meanings in some contexts. When Dawkins refers to "selfish genes" he is using both words metaphorically. He means any bit of DNA that's responsible for a phenotype that can be acted on by natural selection.

When Orgel & Crick refer to "Selfish DNA: the ultimate parasite" they are referring specifically to transposons and viruses that are "selfish" in the sense they act only for their own survival without regard to the needs of the organism. This is the same meaning used by Doolittle & Sapienza when they wrote about "Selfish genes" (Orgel and Crick, 1980; Doolittle and Sapienze, 1980). This distinction between different meanings of "selfish" and "gene" was hashed out in a series of paper back then [see, Selfish genes and transposons]. It takes a bit of work to understand what's going on but that's what you are supposed to do if you are attacking selfish genes.
A more persuasive counterargument is therefore needed. Recent experimental work has provided us with precisely that. The more we examine non-protein-coding DNA the more evidence we find that an overwhelming 80% is transcribed to form RNAs, and that around 20% of those are already known to have function. It was far too premature to dismiss the great majority of the human genome as junk.3
This is called having your cake and eating it too. First, you declare that no experiments could prove or disprove the existence of junk DNA. Then you promote an experiment that presumably does just that. The experiment confirms your bias; namely, that most of our genome is functional and that explains species diversity. Naturally, in order for this logic to work you have to ignore any experiments that support junk DNA or any criticisms of the experiment you mention. Denis Noble does that very well.
This also raises questions about what precisely is a gene. In the original sense defined by Johansson and 1919 1909 (see chapter 5) a gene is anything that contributes to inheritance. At the least, therefore, all the DNA that does that should be regarded as genes. It is too restrictive to define 'gene' as only protein-coding DNA. On a relativistic view we should, however, go even further than that. As we have seen from Waddington's and other experiments, the whole pattern of the genome is relevant to inheritance. The real problem with the gene-centered view is that it ignores the property of the genome as a whole. These overall patterns may have functional significance through the eyes of a higher-level analysis at which functional organization and processes appear.
It's amazing to me that critics of Dawkins can be so confused. When Dawkins talks about selfish "genes" he is using the word "gene" to mean exactly what Johansson meant more than one hundred years ago. Here's how Dawkins himself explains it in The Selfish Gene (p. 28).
A gene is defined as any portion of chromosomal material that potentially lasts for enough generations to serve as the unit of natural selection.
How could that be any clearer? Dawkins has no problem incorporating non-protein-coding molecular genes into selfish gene theory.

The problem with evolution critics like Denis Noble is twofold: (1) they believe that selfish gene theory is equivalent to the Modern Synthesis and that it represents the dominant view of 21st century evolutionary biologists and (2) they think the way to attack that theory is to focus on the meaning of the word "gene." In this sense, Denis Noble's thinking is not much different than that of most philosophers of biology, which leads me to believe that those philosophers are relying on popular books for their knowledge of evolutionary theory.

For the record, my view of current evolutionary theory is based on population genetics at the lowest level. This is the level of DNA and the variants that we are concerned with are alleles, not genes. Alleles can be found within genes or in other parts of the genome. This includes functional elements such as centromeres, regulatory sequences, and origins of replication that aren't "genes." It certainly includes non-protein-coding genes such as those for snRNAs, microRNAs, and tRNAs. Evolution can also occur at the lowest level by changes in allele frequencies within junk DNA. The main mechanisms of evolution are natural selection and random genetic drift.

Alleles can beneficial, detrimental, or effectively neutral. Population size is important. The selfish genes of Dawkins are just one part of evolution at the DNA level. There are many important parts of evolutionary theory that deal with higher levels such as speciation.

The current model of evolution is not gene centric as most of its opponents argue. It is based on population genetics, to be sure, but the appropriate definition of evolution is "change in allele frequency" not change in gene frequency. You could say that it's DNA centric but even that's an exaggeration because it's mostly population centric.

But the purpose of this post is not to engage in ridiculous quibbles about the meaning of evolutionary genes and molecular genes and why they aren't the same. Nor is it meant as a critique of current evolutionary theory. The purpose is to see how Denis Noble interprets the junk DNA controversy in order to get a measure of his ability to understand and explain complex issues in evolutionary biology.

I now have a good understanding of his ability.


1. Denis Noble first defines the molecular definition of a gene as, "a sequence of DNA that is transcribed to produce a functional product." That's remarkably similar to the definition I prefer, "A gene is a DNA sequence that is transcribed to produce a functional product" [What Is a Gene?]. Shortly after that he reverts to attacking the molecular definition because it's restricted to protein-coding regions.

2. A large percentage (>50%) our genome is junk DNA derived from pseudogenes, defective transposons, and defective viruses. These sequences were once functioning elements but they can no longer be referring to as "selfish" DNA in any meaningful way.

3. Noble inserted two references in this paragraph. The first was in support of his claim that 20% of RNAs are known to have function. The reference is to an article on ENCODE published in Science in 2004!!! The second reference supports his claim that it's to premature to conclude that most of our genome is junk. That reference is ... wait for it ... Nessa Carey's book "Junk DNA"!!! It's clear that Noble's knowledge of this topic is very superficial.

Doolittle, W.F., and Sapienza, C. (1980) Selfish genes, the phenotype paradigm and genome evolution. Nature, 284:601-603. [PDF]

Orgel, L.E., and Crick, F.H. (1980) Selfish DNA: the ultimate parasite. Nature, 284:604-607. [doi: 10.1038/284604a0]


19 comments :

Eric said...

1. Noble doesn't understand the cause of diversity, so he claims that diversity is caused by his favorite hobby horse.

2. Makes the false assumption that RNA transcription is a valid indicator of function.

3. Creates a strawman to beat on in order to make his ideas look important.

Those three flaws are becoming all too common in the EES fringe.

Unknown said...

You won't be able to hand wave them away for much longer. Dinis Noble is being taken more seriously, so is EES thanks to actual biological experiments.

Unknown said...

Debate Denis please, in public if can.

John Harshman said...

EES?

Paul Nelson said...

Extended Evolutionary Synthesis.

John Harshman said...

What are the actual biological experiments, and shouldn't that be capitalized?

Joe Felsenstein said...

Dennis N is so devious that he has arranged to have his last name spelled two different ways in your post!

Larry Moran said...

Thanks. Fixed.

Larry Moran said...

That would be very difficult. I've heard him speak at two different meetings and he mostly wants to talk about biological relativity and the evils of reductionism. I agree with him that selfish gene theory is inadequate but it's very difficult to explain why there's a better theory if he doesn't even recognize its existence.

He's a human physiologist and he promotes the view that you can't explain evolution unless you understand that it needs to explain tissues and organs. His idea is that cells are more than just DNA and organs are more than just a collection of cells. It would be very hard to explain to an audience why this has no bearing on evolutionary theory.

The success of EES proponents lies partially in their shotgun approach to criticizing evolutionary biology. In this sense they are very similar to creationists. Debating them is like playing whack-a-mole. The other similarity is that both groups are very good at completely ignoring any science that doesn't fit into their worldview. That's another reason why debates are so difficult.

One of the most important rules of debating is that both sides should be able to switch sides and present the best case of their opponents. I'm pretty sure I could do this with the EES side but they couldn't.

Georgi Marinov said...

He's a human physiologist and he promotes the view that you can't explain evolution unless you understand that it needs to explain tissues and organs.

Interesting that you pick on that.

This is still a point many will disagree with, but I find it quite difficult to refute, and is also in my view the most fundamental insight of the selfish gene approach to evolution -- because we are the organisms, we tend to get the relationship between organism and genetic material backwards, i.e. the relationship between the two is much more accurately described by noting that we exist in order to propagate the genetic material than by focusing on the fact that the genetic material codes for our development.

And whether you subscribe to the simplistic version of the selfish gene theory or you have a firm grasp of the sophisticated actual modern evolutionary theory, that picture does not change much.

The EES looks to me to be at its core a reaction of revulsion to that insight and an attempt to go back from a gene-centered view of evolution to an organism-centered one. They actually explicitly state that on occasions, e.g. here:

http://rspb.royalsocietypublishing.org/content/282/1813/20151019

Anyway, someone who is a physiologist would obviously be more inclined towards the organism-centered view.

txpiper said...

"he promotes the view that you can't explain evolution unless you understand that it needs to explain tissues and organs"

Well, that's the deep end of the pool. Genomes don't perpetuate themselves. Organisms do.

Anonymous said...

"Genomes don't perpetuate themselves. Organisms do."

Genomes do perpetuate themselves, by making organisms that succeed in passing on those genomes. We don't understand evolution unless we realize that it all comes back to genes and differential perpetuation of their alleles.

Although the book has often been misinterpreted because of its title, that was the point of The Selfish Gene, in my opinion.

We'd make another serious mistake if we ignored organism-level traits and events, of course. At the time it was written, though, the book was a useful correction for lay people and many scientists -- including me, from my understanding of evolution at that time. (I've learned a lot since.)

Eric said...

Bibi,

By what measure is Noble "being taken more seriously"? Devoid of any supporting info, your comment seems to be a throwaway.

CrocodileChuck said...

The histone proteins on the book cover are v unrealistic - they look like plastic buttons.

Can't he pay to use an image by Drew Berry @ WEHI, or XVIVO? ;)

http://www.nova.org.au/sites/default/files/images/people-and-medicine/epigenetics/nucleosome-Drew-Berry-animation-2.PNG

Mong H Tan, PhD said...

RE: Medical physiologist vs Molecular biochemist on “evolution”, “junk DNA”, "selfish genes", etc!?

LAM: "I now have a good understanding of his ability." -- But not his new ideas of a more dynamic evolutionary theory (ET) so as to include everything that has ever associated with the biogenesis and the history of life!?

General comment: I think LAM’s statement is exaggerated, because from the commentary above, he clearly has misconstrued DN’s definitions of “evolution” and “junk DNA”, etc; and with which LAM has refuted fundamentally the DN’s more dynamic ET as follows: “He thinks that life is characterized by something he calls "Biological Relativity."[1] I don't disagree. He also thinks that [ET] needs to incorporate everything that has ever happened in the history of life.[2] That's where we part company.” Now let me present more specific comments, as serially itemized below:

1] "Biological Relativity" [(BR)] -- I also agree to this dynamic view of ET, as it is what DN means by “evolution” -- including biogenesis -- whereby the engine of ET began to activate a cascade of “organic relativity, inter-reactivity, viability, vitality, networks, etc” namely the "Dance[s] to the Tune [or Symphony] of Life" (edits in parenthesis, mine) etc, with which DN has titled his book as his view on “life and its processes” philoscientifically from an empiricist physiologist perspective.

2] “..to incorporate everything..” -- I think by this: DN means that “everything” should also include the so-called “junk DNA”; and that this enormous junk DNA (95% of our genome) could be used as a reservoir of “backup” genetic materials in the history of our genome, otherwise its abundance could not have been endogenously incorporated and retained therein, and thereof, since the geo-biochemical formation, organization, and evolution of life (including our genome) over eons ago on Earth, probably in prior to the Precambrian period, as viewed from an evolutionary (evo) developmental (devo) geo-biochemist, geobiologist, geneticist perspective!?

3] DN: "With just a few differences, virtually all the same proteins are made using the same germline genome templates." -- I think DN has over-generalized the protein synthesis processes in multicellular organisms: As empirically we still have no comparative studies of the gene-expressions and their subsequent processes in, and between germ cells and somatic cells or even in or among different types of tissues or organs; and even in all the subsequent somatic cell lineages or tissues, their each subsequent protein synthesis processes could be diverse, dynamic, and diverged along and among their each cellular generations, differentiations, maturations, and functions in and among each cell lineages, tissues, or organs, as observed from the evo-devo embryologist, cytologist, histologist, endocrinologist, geneticist, physiologist perspectives!? -- [To be continued below] --

Mong H Tan, PhD said...

-- [Continued from above] -- RE: Medical physiologist vs Molecular biochemist on “evolution”, “junk DNA”, "selfish genes", etc!?

4] LAM: “It's because of differences in the expression of those genes during development. I don't find that difficult to explain.” -- I think this is an oversimplification of the complex dynamic "Dance[s] to the [Symphony] of Life" thesis (or BR) as commented in 1 above; thus DN has found it difficult to explain, as commented in 3 above: with which he has tried propose a more complex dynamic evo-devo mechanism of BR theory of evolution so as to redirect and replace the hierarchical physicalist, neo-darwinist, reductionist gene-centrism of ET in biology.

5] LAM: “We don't need to look for extraordinary explanations when transcription factors and regulatory sequences—known since the 1960s—are quite capable of creating diversity.” -- On the contrary, the “central dogma” theory of gene expression and regulation mechanisms does not directly concern with the recently discovery of specific epigenetic mechanisms; whereas epigenetics has already been proven efficiently so as to explain many a disease and/or health issues, especially in the biomedical discipline, a field that has clearly advanced in research and development biotechnologies as viewed from the multidisciplinary physiologist, geneticist, endocrinologist, neurologist, immunologist perspectives!?

6] LAM: “I'm also surprised that after all the public controversy over ENCODE and junk DNA, he still thinks that pervasive transcription rules out junk DNA.” -- On the contrary, DN merely states: “That idea of 'junk' DNA has now itself been junked as we have found that the great majority of the sequences [in junk DNA] are transcribed into RNAs.” This could be one of the reserve or backup functions of the junk DNA as I commented in 2 above!?

7] LAM: “When Dawkins refers to "selfish genes" he is using both words metaphorically. He means any bit of DNA that's responsible for a phenotype that can be acted on by natural selection.” -- I think LAM is arguing in and with himself from the faulty view of "selfish genes" thesis. In any scientific debates, anyone using metaphors or semantics or rhetorics is clearly a self-defeatist in one’s pursuits and inquiries of our multidisciplinary science and philosophy issues: Just as DN has refuted in his book that “[t]he words selfish junk etc. are, of course, metaphors. More importantly they are empirically empty metaphors when applied to sequences of DNA. No conceivable experiment could validate or invalidate them, as explained in chapter 5.” -- [To be continued below] --

Mong H Tan, PhD said...

-- [Continued from above] -- RE: Medical physiologist vs Molecular biochemist on “evolution”, “junk DNA”, "selfish genes", etc!?

Besides philoscientifically the term “natural selection” (NS) in and of itself is a “metaphor” (an accepted expression of the time) that Darwin had deployed but not proven as a “scientific mechanism” in his naturalist phenomenology masterpiece "On the Origin of Species" (1859) -- or more completely with even more metaphors -- "On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life". This is why at the Royal Society Meeting last November (2016) wherein no empiricists had been encouraged to utter NS as a “scientific mechanism”.

Thus philoscientifically, the Dawkinsian “selfish gene” definition as one that “any bit of DNA that's responsible for a phenotype that can be acted on by [NS]” could not be falsified or validated scientifically or empirically! On the contrary, both evo-devo biology and genetics have shown that none a phenotypes are caused by a “single gene” alone in multicelled organisms; whereas many a phenotypes or cell-types would generally involve in the expression of a multiple cooperative genes, such a multiple associative genes that eventually involve in building up or giving rise to the expression or composition of a phenotype, tissue-type, trait, or even a behavior style as commented in 3 above!? As such the BR of multiple evo-devo genetic cooperativity or inter-reactivity is IN, while the “selfish gene” the pseudogenetic self-determinist or defeatist selectivity is OUT, in the current 21st century and beyond!?

8] LAM: "[T]hat most of our genome is functional and that explains species diversity." -- I think this assumption is over simplistic (without considering that 95% junk DNA as strand-scaffolding materials) and also contradictory without further investigations in embryology and germline genetics, as commented in 2 above. Besides speciation of multicelled organisms may be observed at the somatic genome level, whereas each species may have been conceived or originated and preserved at the germ cell or gamete level, as viewed from both the evo-devo geobiologist and embryologist perspectives.

This is why we have observed the sudden outburst of diverse species or speciation phenomenon in the Cambrian period, as viewed from a paleontologist geologist perspective. Such a speciation phenomena couldn’t be explained by Darwinism alone; whereas they have certainly been misconceived, and hijacked, by neo-Darwinism par excellence of the 20th century past; even to the present days! -- Just as DN has warned: "That the metaphors are empty from the standpoint of empirical science does not mean they have no impact. On the contrary, they have had, and still have, very persuasive impact on the way in which many people think about biology [and genetics]." (See also Comment 7 above; and more below).

Further, LAM’s neo-Darwinism-biased understanding of the genome and species diversity explanations is totally overshadowed by DN’s BR in both evo-devo biology and genetics: "On a relativistic view we should, however, go even further than that. As we have seen from Waddington's and other experiments, the whole pattern of the genome is relevant to inheritance. The real problem with the gene-centered view is that it ignores the property of the genome as a whole. These overall patterns may have functional significance through the eyes of a higher-level analysis at which functional organization and processes appear [even without expression in 95% junk DNA]." (Edits in parenthesis, mine). -- [To be continued below] --

Mong H Tan, PhD said...

-- [Continued from above] -- RE: Medical physiologist vs Molecular biochemist on “evolution”, “junk DNA”, "selfish genes", etc!?

9] Dawkins: "A gene is defined as any portion of chromosomal material that potentially lasts for enough generations to serve as the unit of natural selection." -- I think LAM is fixated or “dawkinsieged” or stunted by the mid-20th-century Dawkinsian ambiguous rhetoric or the gene-centric theory of ET (gcET): One which is defined in, and confined by, metaphors and rhetorics; and which hasn’t or couldn’t be scientifically or empirically falsified nor validated at all since 1976!? LAM further adds that "Dawkins has no problem incorporating non-protein-coding molecular genes into selfish gene theory." -- Whereas Dawkins never did; even if he does, it would be totally in conflicts with his now firmly-fossilized gcET; or further metaphorizing it as the “self-replicator” gcET: the gcET that has been derived from the “central dogma” theory and neo-Darwinism, in his extreme attempt to anthropomorphize or reductively upsurge and replace the “common ancestor” hypothesis in Darwinism, the one naturalist inductive form of ET that was first speculated by Charles Darwin (1809-82) in 1859 (also see Comment 7 above)!?

10] LAM: "In this sense, Denis Noble's thinking is not much different than that of most philosophers of biology, which leads me to believe that those philosophers are relying on popular books for their knowledge of [ET]." -- I think this conclusive remark doesn’t apply to DN’s philosophy and knowledge of ET at all: As he is clearly an able, aspiring, physiologist-trained, and empiricist philosopher of science and biology; one who is well-versed so as to present and articulate a more “dynamic evo-devo genome” network of ET, the “Biological Relativity: Evo-devo Dances to the Symphony of Life” (edits mine) with more philoscientific insights, vigors, and specifics -- but certainly not with more irrelevant metaphors, semantics, or rhetorics -- than the prevailing bio-reductionist pseudoscientific gcET in neo-Darwinism, or post-Darwinism, since the late 19th-20th centuries past!? (See also Comments 8 - 9 above).

For the record” -- I think LAM has fallen hard for the fallacies of the Modern Synthesis of ET: One neo-Darwinism that was consensually misconceived and formulated in 1930s-40s and molecularized in 1960s-70s; and one ET which stipulates that "[ET can be, and still] is based on population genetics at the lowest level[;]" and that "[t]he main mechanisms of evolution are [grossly quantifiable by Darwin’s hypothetical or metaphorical means of] natural selection [since 1859] and [artificially-derived] random genetic drift [since 1920s-30s, thus giving rise to the physicalist, reductionist, and mathematically-derived Modern Synthesis of ET thereon and thereafter since 1930s-40s]." -- (Edits in parenthesis, mine; also see Comment 9 above).

Best, Mong 5/24/17usct01:27; practical public science-philosophy critic (since 2006).

Unknown said...

I’m having a difficulty and it seems to me it has to do with the approach.

If evolution is defined as changes in DNA, then evolution is what happens to DNA.
This gives us a stochastic process (due to chancy replication and replication errors) where ‘natural selection’ can be seen as a rather small (but not insignificant) feedback to the process.

Evolution is what happens to DNA and ‘natural selection’ is a feedback in that process. That makes a lot of sense and it includes any and all changes to DNA and any sort of ‘feedback’ from the environment one might want to include in the notion of ‘natural selection’.

However, if I view evolution as what happens to ‘genotypes’ or ‘phenotypes’, and I want to make ‘natural selection’ a driver instead of a feedback…

Suddenly that view of things seems rather backwards. I’m thinking it is actually incoherent.
Is it really as incoherent as it appears to me now?

A different but not disrelated paper- Apparently teaching genetics before evolution is a good idea.
https://www.sciencedaily.com/releases/2017/05/170523144131.htm

(Also— would the term ‘hobbyhorse’ be a reasonably accurate representation of the relationship Dr. Moran has with ‘junk DNA’ or not?)