Saturday, March 15, 2014

Philip Ball writes about molecular mechanisms of evolution

It's been almost a year since I commented on an Nature article by Philip Ball [see DNA: Nature Celebrates Ignorance]. Here's part of what I wrote back then ...
The main premise of the article is revealed in the short blurb under the title: "On the 60th anniversary of the double helix, we should admit that we don't fully understand how evolution works at the molecular level, suggests Philip Ball."

What nonsense! We understand a great deal about how evolution works at the molecular level.
The worst thing about the Nature article was the misuse of the Central Dogma of Molecular Biology. The second worst thing was the "revelation" that genes are regulated by regulatory sequences as if that was a new discovery. (He mentions the ENCODE results.)

The best thing about the article was that Philip Ball seemed to understand random genetic drift and Neutral Theory and seemed to realize that there is more to evolution than just natural selection. However, his main theme was that there's lots we don't know about evolution and somehow the general public isn't being told about "... doubts, debates and discussions that are leaving the putative 'age of the genome' with more questions than answers."

My own view is that we are far, far, more certain about molecular mechanisms of evolution than Philip Ball imagines. Most of what he perceives as new and controversial was actually settled many decades ago in the 1960s.

Philip Ball read the recent Science article by Rosenberg and Queitsch (2014). I've already pointed out the deficiencies in that article [How does molecular biology overthrow the Modern Synthesis?]. Let's see how Philip Ball responds to that article in light of the feedback he received when he published last year. Here's a link to his recent blog post: Molecular mechanisms of evolution.

Let's begin by reminding ourselves that the old Modern Synthesis has been substantially revised and updated with the development of Neutral Theory and the recognition that random genetic drift is a major player in evolution. Those changes to modern evolutionary theory took place over forty years ago.

Here's what Philip Ball thinks today. Keep in mind that Philip Ball is a science writer—it's part of his job to keep up with the science he writes about.
“Molecular mechanisms that generate biological diversity are rewriting ideas about how evolution proceeds”. I couldn’t help noticing how similar that sounds to what I was saying in my Nature article last spring, “Celebrate the unknowns”. Some people were affronted by that – although other responses, like this one from Adrian Bird, were much more considered. But this is the claim put forward by Susan Rosenberg and Christine Queitsch in an interesting commentary in Science this week. They point out (as I attempted to) that the “modern synthesis” so dear to some is in need of some modification.
As far as I'm concerned, there's nothing in the Rosenberg and Queitsch paper that requires modification of current evolutionary theory as described in modern textbooks. That theory, let me remind you, has already moved far beyond the 1930s version of the Modern Synthesis.

Philip Ball continues ...
“Among the cornerstone assumptions [of the modern synthesis]”, say Rosenberg and Queitsch, “were that mutations are the sole drivers of evolution; mutations occur randomly, constantly, and gradually; and the transmission of genetic information is vertical from parent to offspring, rather than horizontal (infectious) between individuals and species (as is now apparent throughout the tree of life). But discoveries of molecular mechanisms are modifying these assumptions.” Quite so.

This is all no great surprise. Why on earth should we expect that a theory drawn up 80 or so years ago will remain inviolable today?
This is the part that really makes me angry. Why in the world do Philip Ball, Susan Rosenberg and Christine Queitsch think that our 21st century view of evolution is 80 years old? It's because they haven't kept up.
As I am sure Darwin expected, evolution is complex and doesn’t have a single operative principle, although obviously natural selection is a big part of it. (I need to be careful what I say here – one ticking off I got was from a biologist who was unhappy that I had over-stressed natural selection at the molecular level, which I freely confess was a slight failure of nerve – I have found that saying such things can induce apoplexy in folks who see the shadows of creationism everywhere.) My complaint is why this seemingly obvious truth gets so little airplay in popular accounts of genetics and evolution. I’m still puzzled by that.
There are two problems here. Why has this "seemingly obvious truth" escaped the notice of some scientists, like, I suspect, Rosenberg and Queitsch, and why doesn't the general public have a better understanding of current evolutionary theory. (BTW, I suspect that I'm the "biologist" he refers to since we had an exchange of emails.)

We can blame the second problem on science writers who have not made the effort to keep up with evolutionary biology and population genetics. They don't explain it to the general public because they don't get it themselves.

The first problem is our fault. We are letting students graduate with Ph.D.s in biology without understanding evolution. It's no wonder that when they start their own research labs they perpetuate these misunderstandings of evolution among their own students.

Maybe Philip Ball has seen the light. Maybe he now realizes that the old-fashioned, 80-year-old version of the Modern Synthesis was abandoned by the experts a long time ago and that he (Philip Ball) just didn't notice. That would be nice ...
I realise now that kicking off my piece with ENCODE was something of a tactical error (even though that study was what began to raise these questions in my mind), since the opposition to that project is fervent to the point of crusading in some quarters. (My own suspicion is that the ENCODE team did somewhat overstate their undoubtedly interesting results.) Epigenetics too is now getting the backlash for some initial overselling. I wish I’d now fought harder to keep in my piece the discussion of Susan Lindquist’s work on stress-induced release of phenotypic diversity (S. Lindquist, Cold Spring Harb. Symp. Quant. Biol. 74, 103 (2009)), which is mentioned in the Science piece – but there was no room.
Doesn't look promising. The real challenges to the 80-year-old Modern Synthesis come from Neutral Theory and random genetic drift. The things that Rosenberg and Queitsch write about are not new and not significant.

If science writers really want to educate the general public, they need to stop publicizing the trivial and ridiculous claims about overthrowing the Modern Synthesis coming from scientists who don't understand that the real revolution took place before they became scientists.


Rosenberg, S.M. and C. Queitsch (2014) Combating Evolution to Fight Disease. Science 343:1088-1089. [doi: 10.1126/science.1247472]

11 comments :

  1. "Maybe he now realizes that the old-fashioned, 80-year-old version of the Modern Synthesis was abandoned by the experts a long time ago"

    Theories do change over time, but there is a bit of irony in you saying that given that is almost word-for-word what people respond when you claim that that the present Modern Synthesis has "ossified" to become selectionist.

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  2. The first problem is our fault. We are letting students graduate with Ph.D.s in biology without understanding evolution. It's no wonder that when they start their own research labs they perpetuate these misunderstandings of evolution among their own students.

    I fully agree with most of what you say, as I have said many times here. The only reason I myself am not completely ignorant of these issues is personal interest in the subject in combination with blogs like yours making me pay more attention to it. But how exactly do you envision the real-world fix for the problem?

    There is absolutely no incentive in the current system to train students in more than the hands-on technical skills necessary to do day-to-day research. And you do need that training, but you also need a lot more if your PhD is to be worth what it's supposed to be in terms of intellectual development. It is entirely up to your adviser to do that, if he/she is willing and has the time. I will not dispute the claim that there are advisers who are neither willing nor capable of doing that, but I think the largest group is the one of those who are willing but simply do not have the time and energy to engage in discussion not directly related to the specifics of the current research going on in their labs, because of all the obligations they have to meet. And with funding continually squeezed and the ever encroaching administrative duties creep, there is no escape in sight.

    It would greatly help if there was an NIH mandate to significantly beef up the first two years of PhD programs with theoretical coursework (it would help research too - some more math, statistics and computer science would not hurt anyone, and everyone having deeper understanding of evolution would open up new research directions when people put their work in a wider perspective). But that's time away from the bench, i.e. the direct return of investment goes down...

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    1. I don't have a solution. Some of us try to challenge graduate students when they give talks that reveal a lack of knowledge about evolution (and/or fundamental biochemistry). Some of us try to raise the issue during Ph.D. orals but, by then, their papers have been published in leading journals and it's difficult to convince other members of the committee that something is wrong.

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  3. In reference to abiogenesis, Dr. Szostak states that challenges remain. http://bit.ly/AbiogenesisChallengesRemain Thus, it may be appropriate to state that we do not fully understand. Next, the challenges to ENCODE are based on models of population genetics, and that is probably less reliable than directly measurable findings used by the ENCODE authors.

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    1. Next, the challenges to ENCODE are based on models of population genetics, and that is probably less reliable than directly measurable findings used by the ENCODE authors.

      The objections to ENCODE are not just based on population genetics, but also observational and experimental biochemistry and molecular genetics. If you think the ENCODE objections are purely based on pop gen then you need to do some homework.

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  4. Psoriasis: Abiogenesis is effectively unrelated to questions of contemporary evolution.

    The ENCODE results are not more reliable than pop gen. If by function you mean "having an actual effect in an organism", several basic facts prelude the ENCODE designation of function. You'll have to read a detailed post for a full discussion, but given the vast amount of "functional" variation they seem to describe, which has no discernible effect when duplicated or deleted or mutated, red flags should immediately go up. At best, the fitness effects are necessarily less than 1/2Ne, thus are selectively neutral.

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  5. It's not that our century view of evolution is 80 years old. It's that the modern synthesis is 80 years old. What the term "the modern synthesis" refers to is a matter of terminology. Some hold that it refers to what Huxley said. Others use the term in different ways. If the modern synthesis is defined as a moving target, there seems to be a lack of landmark publications updating it. Where was neutral theory incorporated into it? Where was symbiogenesis incorporated?

    The "modern synthesis" has no foundation maintaining and updating it. Maybe that's because it died many years ago and its current gyrations are merely zombie-like death throes.

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  6. The argument for keeping the name Modern Synthesis while one incorporates new phenomena is this:
    1. Otherwise every time John Blotz came along with a new phenomenon he could strut around publicizing the fact that he, the great Blotz, had invalidated the evolutionary synthesis, and now we had the (ta-da!) Blotzian Synthesis. But he would be shocked a year or two later when Jane Schmerz came along and invalidated the Blotzian Synthesis in favor of the new Schmerzian Synthesis. And so it would go, until everyone was totally confused, and most people were several syntheses behind.
    2. Meanwhile the public would be continually told that all that stuff they learned in secondary school, about mutation and natural selection and some other evolutionary forces, was all wrong, because now we had the Blotzian (er, oops, actually the Schmerzian) Synthesis instead.

    It would be great for Blotz's and Schmerz's egos (temporarily) but a disaster for everyone else.

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    1. Why not just call it "evolutionary theory"? As soon as you give it a specifc name like "Modern Synthesis" you are locking in a particular version of evolutionary theory that's peculiar to a place and time.

      The Modern Synthesis is a product of the 1940s. Scientists like Mayr, Simpson, Huxley, Haldane, and Dobzhansky would not recognize the evolutionary theory found in modern textbooks. They would be shocked to see a whole chapter on random genetic drift, for example. Even Wright wouldn't recognize his own creation.

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    2. Small disagreement: Wright would recognize his own creation -- in retirement he was in Madison, Wisconsin, where Motoo Kimura did his Ph.D. thesis with Jim Crow. Wright was frequently in touch with Crow, had his office in the same department, and had ample opportunity to hear of Kimura's advocacy of neutral mutation. Wright wrote a four-volume review of theoretical and empirical population genetics in the period 1968 - 1984, and did discuss neutral mutation as an explanation of genetic diversity. He had less chance to deal with molecular differences between species.

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    3. Why not just call it "evolutionary theory"? As soon as you give it a specifc name like "Modern Synthesis" you are locking in a particular version of evolutionary theory that's peculiar to a place and time.

      Couldn't we have a name that accommodated changes as pieces were added to the theory? "Newtonian" physics had a good long run -- it was not discarded immediately once the periodic table was understood, or once thermodynamics was invented, or statistical mechanics, or electromagnetism taken into account. Having a term like that would be desirable.

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