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Monday, December 12, 2022

Did molecular biology make any contribution to evolutionary theory?

Some evolutionary biologists think—incorrectly, in my opinion—that molecular biology has made no contributions to our understanding of evolution.

PNAS published a series of articles on Gregor Mendel and one of them caught my eye. Here's what Nicholas Barton wrote in his article The "New Synthesis".

During the 1960s and 1970s, there were further conceptual developments—largely independent of the birth of molecular biology during the previous two decades (15). First, there was an understanding that adaptations cannot be explained simply as being “for the good of the species” (16, 17). One must explain how the genetic system (including sexual reproduction, recombination, and a fair meiosis, with each copy of a gene propagating with the same probability) is maintained through selection on individual genes, and remains stable despite mutations that would disrupt the system (17, 19, 20). Second, and related to this, there was an increased awareness of genetic conflicts that arise through sexual reproduction; selfish elements may spread through biased inheritance, even if they reduce individual fitness (19, 21, 22). In the decade following the discovery that DNA carries genetic information, all the fundamental principles of molecular biology were established: the flow of information from sequences of DNA through RNA to protein, the regulation of genes by binding to specific sequences in promoters, and the importance of allostery in allowing arbitrary regulatory networks (23, 24). Yet, the extraordinary achievements of molecular biology had little effect on the conceptual development of evolutionary biology. Conversely, although evolutionary arguments were crucial in the founding of molecular biology, they have had rather little influence in the half-century since (e.g., ref. 25). Of course, molecular biology has revealed an astonishing range of adaptations that demand explanation—for example, the diversity of biochemical pathways, that allow exploitation of almost any conceivable resource, or the efficiency of molecular machines such as the ribosome, which translates the genetic code. Technical advances have brought an accelerating flood of data, most recently, giving us complete genome sequences and expression patterns from any species. Yet, arguably, no fundamentally new principles have been established in molecular biology, and, in evolutionary biology, despite sophisticated theoretical advances and abundant data, we still grapple with the same questions as a century or more ago.

This does not seem fair to me. I think that neutral theory, nearly neutral theory, and the importance of random genetic drift relied heavily on work done by molecular biologists. Similarly, the development of dating techniques using DNA and protein sequences is largely the work of molecular biologists. It wasn't the adaptationists or the paleontologists who discovered that humans and chimpanzees shared a common ancestor 5-7 million years ago and it wasn't either of those groups who discovered the origin of mitochondria.

And some of us are grappling with the idea that most of our genome is junk DNA, a question that never would have occurred to evolutionary biologists from a century ago.

Barton knows all about modern population genetics and the importance of neutral theory because later on he says,

If we consider a single allele, then we can see it as “effectively neutral” if its effect on fitness is less than ∼1/2Ne. This idea was used by Ohta (54) in a modification of the neutral theory, to suggest why larger populations might be less diverse than expected (because a smaller fraction of mutations would be effectively neutral), and why rates of substitution might be constant per year rather than per generation (because species with shorter generation times might tend to have large populations, and have a smaller fraction of effectively neutral mutations that contribute to long-term evolution). Lynch (21) has applied this concept to argue that molecular adaptations that are under weak selection cannot be established or maintained in (relatively) smaller populations, imposing a “drift barrier” to adaptation. Along the same lines, Kondrashov (55) has argued that deleterious mutations with Nes ≈ 1 will accumulate, steadily degrading the population. Both ideas seem problematic if we view adaptation as due to optimization of polygenic traits: Organisms can be well adapted even if drift dominates selection on individual alleles, and, under a model of stabilizing selection on very many traits, any change that degrades fitness can be compensated.

Barton may think that the drift-barrier hypothesis is "problematic" but it certainly seems like a significant advance that owes something to molecular biology.

What do you think? Do you agree with Barton that, "... the extraordinary achievements of molecular biology had little effect on the conceptual development of evolutionary biology."


Joe Felsenstein said...

Nick's comment that the drift barrier is "problematic" invokes the case of a polygenic phenotype whose value is affected by the sum of effects of a large number of loci that contribute roughly additively to the trait. In such as case he is right: the overall phenotype can be under strong selection for an optimum value while individual loci can drift, subject to the sum of their effects not changing much." But the cases for which Michael Lynch has invoked the drift barrier are not sums of effects of single loci, but large chromosome rearrangements in single events. These two cases need to be distinguished.

Larry Moran said...


I was under the impression that the drift-barrier also applies to a single locus with a small selection coefficient. I don’t see much of a difference between nearly neutral theory and the drift barrier hypothesis.

But that’s a minor issue in Barton’s article. The main issue is his focus on adaptation in large animals. This narrow focus leads to a great deal of confusion over the meaning of evolution and it explains why few people understand molecular evolution. It also explains why Barton isn’t interested in molecular evolution and doesn’t recognize the contributions of biochemists and molecular biologists.

It’s unfortunate that undergraduate education in evolution is mostly taught by ecology & evolution professors.

John Harshman said...

One very prominent way in which molecular biology has affected evolutionary biology, which you only briefly and obliquely hint at, is molecular phylogenetics and all the additional insights that come from mapping data onto the resulting phylogenies. The human-chimp relationship is an infinitesimal piece of all that.

Jonathan Badger said...

Besides molecular phylogenetics, genomics has added a lot to our knowledge of evolution. For example, the time of the human genome project there were assertions that the human genome had a lot of recent transfer from bacteria, as they had up to that time only been identified in bacteria, but most of those have since been seen in the genomes of many other eukaryotes as well. And conversely many genes thought to be animal only have been seen in bacteria.

Donald Forsdyke said...


Shortly after Nick Barton's "New Synthesis" article in PNAS (July 2022), his group submitted a paper on "What is reproductive isolation?" to the Journal of Evolutionary Biology (Westram et al. 2023). I have addressed his synthesis viewpoint (and much more) in a paper that is presently under review (see SSRN preprint).

The latter paper raises historic issues that Nick's group seems to have overlooked. Their JEB paper gave some support to this conclusion, since it dated the first emergence of the term "reproductive isolation" in an evolutionary context to Emerson (1935) at the University of Chicago.

Happily, following consultation with the Editor and the authors, I am informed by the Editor that Wiley is attaching a correction to the date (actually, at least 1888) to their final published version.

Robert Byers said...

Molecular biology affect on evolutionary biology is simply confiming the original error or lack of imagination for other options for why biology is as it is. Molecular biology follows the same line of reasoning that it can not change suddeenly or rather it has nothing in it to allow sudden changes. if these changes coul;d suddenly happen it would make worthless any extrapolation backwards from the present. Its a complex thing and who says they know it only works in straight lines. i say it does't. molecular biology is useless to explain origins until one has proven the simple idea of slow acting mutations on populations. Any other option makes it useless as a tool for the past.

Joe Felsenstein said...

It’s unfortunate that undergraduate education in evolution is mostly taught by ecology & evolution professors. That seems to be saying that instead it should be taught my molecular biology, cell biology, or genomics professors. You know, the ones who have overwhelmingly been convinced that there is little or no junk DNA. Wasn't someone in their own field writing a book to try to change their minds about that?

Joe Felsenstein said...

The first sentence of my comment today should have been in quotes, as it quotes Larry's comment in this thread. I made the mistake of using HTML "em" tags to try to put it in italic.

Joe Felsenstein said...

... and now the italics reappeared. Whatever.

Larry Moran said...


I think that evolution should be taught by teachers who are familiar with ALL aspects of evolution, including molecular evolution. The best evolutionary biologists should be able to teach population genetics as one of the fundamental parts of evolution. Instead, students are mostly exposed to teachers whose major interest is adaptation to the environment in large animals.

If the course uses a textbook like Futuyma's then all chapters should be covered in a good course on evolution. However, students should not rely on the accuracy of everything in Futuyma's book. I have the 2nd edition (2009) and it contains a lot of misinformation and misleading statements about genomes including, "Most of this noncoding DNA is no longer considered to be the "junk" it was postulated to be in the early 1970s" (p. 525).

popgen wannabe said...

Joe Felsenstein wrote 'In such as case he is right: the overall phenotype can be under strong selection for an optimum value while individual loci can drift, subject to the sum of their effects not changing much.'

This is fascinating, but I don't think I fully understand it. Each locus is itself effectively neutral. Or are they still under the tiniest bit of selection, so that their sum follows something like a normal distribution whose mean does not drift as much as the individual loci? Is this something that has been mathematically modelled?

Joe Felsenstein said...

Yes, under the tiniest bit of selection. Russ Lande pointed this out in a paper in the 1970s: if we have n loci whose effects add up to make a phenotype, and all are segregating for two alleles, there is an n-1-dimensional subspace of gene frequencies in which the phenotypes are all at the same value, say the optimal value. They can genetically drift in that subspace without selection influencing where they go: selection will just act to push them into that subspace.

popgen wannabe said...

Thanks Joe, very helpful.

The part I still don't understand is 'molecular adaptations that are under weak selection cannot be established or maintained in (relatively) smaller populations' (quote from the article).

If the adaptation itself is under extremely weak selection, how does a polygenic basis rescue it from effective neutrality? Or is Barton's point only about adaptations that are themselves strongly selected, while individual alleles contributing to that trait might be weakly selected?

Doug said...

Hi Dr. Moran. I was reading through some of your older blog posts and came across this: "I am not a Darwinist. I prefer a modern pluralist view of evolution as I explain in Evolution by Accident." But the link to your "Evolution by Accident" post is a dead link. Any possibility you have that available to repost? Also any chance you'll post a book review of one of the books in your reading list, "A Gene's-eye View of Evolution"? I'd love to know what you think and about it and how close it is to Dawkin's arguments.

Larry Moran said...


Here's the new link to "Evolution by Accident."

I'm not going to review Agren's book because I'm way too busy right now with my own book. I doubt that I'll ever get around to it because it would take another book to review it properly. On the surface, it looks like it reflects the Dawkins view but if you look more closely you'll see that it's much more radical than Dawkins and much more focused on the molecular gene than on the Mendelian gene that Dawkins prefers.

I'm very disappointed that Agren doesn't seriously address the main objections to adaptationism and the selfish gene concept.