Pharyngula

I was rather surprised yesterday to see so much negative reaction to my statement that there’s more to evolution than selection, and that random, not selective, changes dominate our history. It was in the context of what should be taught in our public schools, and I almost bought the line that we can only teach a simplified version of evolution in grade school, but then it sunk in that I was talking to a group of adults about the standard biological perspective, and their reactions were a mix of total bafflement, indignant rejection, and strange evasive waffling. Well, when should we talk about this stuff, then? Do I have to start making day trips to the local nursing home? Or maybe we should be honest from the very beginning about the complexity of modern evolutionary theory and how it has grown to be very different from what Darwin knew.

First thing you have to know: the revolution is over. Neutral and nearly neutral theory won. The neutral theory states that most of the variation found in evolutionary lineages is a product of random genetic drift. Nearly neutral theory is an expansion of that idea that basically says that even slightly advantageous or deleterious mutations will escape selection — they’ll be overwhelmed by effects dependent on population size. This does not in any way imply that selection is unimportant, but only that most molecular differences will not be a product of adaptive, selective changes.

These theories describe different patterns of the distribution of mutations in populations. This diagram from Bromham & Penny (2003) will help you see the difference.

Selectionist, neutral and nearly neutral theories. a | Selectionist theory: early neo-Darwinian theories assumed that all mutations would affect fitness and, therefore, would be advantageous or deleterious, but not neutral. b | Neutral theory: the neutral theory considered that, for most proteins, neutral mutations exceeded those that were advantageous, but that differences in the relative proportions of neutral sites would influence the rate of molecular evolution (that is, more neutral sites would produce a faster overall rate of change). c | Nearly neutral theory: the fate of mutations with only slight positive or negative effect on fitness will depend on how population size affects the outcome.

Selectionist, neutral and nearly neutral theories. a | Selectionist theory: early neo-Darwinian theories assumed that all mutations would affect fitness and, therefore, would be advantageous or deleterious, but not neutral. b | Neutral theory: the neutral theory considered that, for most proteins, neutral mutations exceeded those that were advantageous, but that differences in the relative proportions of neutral sites would influence the rate of molecular evolution (that is, more neutral sites would produce a faster overall rate of change). c | Nearly neutral theory: the fate of mutations with only slight positive or negative effect on fitness will depend on how population size affects the outcome.

The purple bars are mutations subject to purifying selection — that is, deleterious mutations that are culled from the population. The green bars are mutations subject to positive selection, that confer some advantage to the individual carrying them. That’s all people thought you would have under old school versions of evolution: every change would have some effect on the individual, and would be subject to selection (and then, of course, smart people started to wonder about genetic load and realizing that there were limitations to how much selection a population could tolerate).

Kimura and Ohta proposed, though, that many mutations would be neutral — that is, changes to the sequence of a gene or the protein would have no effect on fitness, and would be effectively neutral. Since the genetic code is degenerate, with most amino acids coded for by more than one triplet, you could have synonymous changes to the DNA that would produce proteins with identical amino acid sequences. Further, protein structure and function may not be as precisely dependent on specific amino acid sequences as many people assume: there are key regulatory and active sites within proteins that are extremely sensitive to small amino acid changes, but other parts of the protein may be much more fault tolerant. That means that under neutral theory, we have to recognize that beige bar, which are mutations that have no effect on fitness.

Under nearly neutral theory, the domain of selection effects shrunk further, because it was realized that quantitatively, small deleterious and advantageous mutations, that is mutations that only conferred a slight difference in reproductive success, would be invisible against a noisy background of chance variation, and therefore could not be seen by selection. That’s the blue bar; mutations that we can see might cause a slight change to the efficiency of an enzyme, for instance, but are not significant enough to cause any difference in reproductive success, or are either lost or fixed by chance.

Now you might try to salvage your faith in the ultimate power of selection by suggesting that the neutral and nearly neutral mutations are really rare and can thus be ignored as negligible, therefore returning us to the world of selection theory…with just a little fuzzy slop around the boundary between the green and blue bars. That’s untenable, though. We have molecular clocks.

When comparing the rates of change between homologous genes in different species, we had a bit of a surprise: they are very roughly, sloppily constant. That shouldn’t be true under pure selection theory, but it turns out to make a lot of sense under nearly neutral theory. There is a tradeoff in the rate of mutations occurring, and in becoming fixed in a population. A very large population size will accumulate more mutations purely by chance, but the probability of a single mutation becoming fixed in the population is reduced under large population sizes. When you do the math, you discover that population size cancels out, and the frequency of novel forms becoming fixed over time is dependent solely on the mutation rate.

Think about that. If you compare two species, the number of nucleotide differences between them is basically going to be simply the mutation rate times the number of generations separating them from their last common ancestor. That’s how we can use a molecular clock to date the time of divergence of two lineages.

Please note: this does not deny that the selection shapes specific traits in a species occurs — we do undergo evolutionary adaptation! It merely says that most of the genetic changes are random. We have to use specific analysis techniques, like the McDonald/Kreitman test, to detect the signature of selection out of the background noise of mutation.

This is just one example of an important concept that is overlooked when your education in evolution focuses solely on one simplistic version of the mechanisms of change. If you didn’t know it, it’s not your fault; I graduated from high school never having the ‘evolution’ word uttered even once by a teacher, so if you’ve heard about natural selection, you’re one up on me. But we can do better. That the high school level of instruction in evolutionary biology is stuck at around 1930 is a bug, not a feature, and we should aim to improve it.

I know, it’s hard when a significant part of the population is stuck in the first millennium BCE, but we shouldn’t use that as an excuse to dumb down education.

Now, because I so enjoyed the chaos that ensued after rejecting one small part of the Modern Synthesis, let me share with you something rather cool. It’s a table from Eugene Koonin’s The Logic of Chance, in which he summarizes some of the big changes between the Modern Synthesis that emerged in the era before molecular biology, and how most molecular biologists view evolution today. I expect an even more glorious freakout because he refers to this positively as a postmodern reassessment, and I know how much everyone loves post-modernism.

Postmodern reassessment of some central propositions of Darwin and Modern Synthesis

Proposition

Postmodern status

The material for evolution is provided primarily by random, heritable variation.

Only partly true. The repertoire of relevant random changes greatly expanded to include duplication of genes, genome regions, and entire genomes; loss of genes and generally, genetic material; HGT [horizontal gene transfer], including massive gene flux in cases of endosymbiosis; invasion of mobile selfish elements and recruitment of sequences from them; and more. More importantly, (quasi) directed (Lamarckian*) variation is recognized as a major factor of evolution.

Fixation of (rare) beneficial changes by natural selection is the main driving force of evolution.

Only partly true. Natural (positive) selection is important but is only one of several fundamental factors of evolution and is not quantitatively dominant. Neutral processes combined with purifying selection dominate evolution, and direct effects of environmental cues on the genome ([quasi] Lamarckian phenomena) are important as well.

The variations fixed by natural selection are “infinitesimally small.” Evolution adheres to gradualism.

False. Even single gene duplications and HGT of single genes are by no means “infinitesimally small,” nor are deletion or acquisition of larger regions, genome rearrangements, whole-genome duplications, and, most dramatically, endosymbiosis. Gradualism is not the principal regime of evolution. [And I would add that even point mutations can have large phenotypic effects. –pzm]

Uniformitarianism: Evolutionary processes have remained largely the same throughout the evolution of life.

Only partly true. Present-day evolutionary processes were important since the origin of replication. However, major transitions in evolution, such as the origin of eukaryotes, could be brought about by (effectively) unique events such as endosymbiosis, and the earliest stages of evolution (pre-LUCA [last universal common ancestor]) partially relied on distinct processes not involved in subsequent “normal” evolution.

Evolution by natural selection tends to produce increasingly complex adaptive features of organisms, hence progress is a general trend in evolution.

False. Genome complexity probably evolved as a “genomic syndrome” cause by weak purifying selection in small populations, not as an adaptation. There is no consistent trend toward increasing complexity in evolution, and the notion of evolutionary progress is unwarranted.

The entire evolution of life can be depicted as a single “big tree.”

False. The discovery of the fundamental contribution of HGT and mobile genetic elements to genome evolution invalidates the TOL concept in its original sense. However, trees remain essential templates to represent evolution of individual genes and many phases of evolution in groups of relatively close organisms. The possibility of salvaging the TOL as a central trend of evolution remains.

All extant cellular life forms descend from very few ancestral forms (and probably one, LUCA).

True. Comparative genomics leaves no doubt of the common ancestry of cellular life. However, it also yields indications that LUCA(s) might have been very different from modern cells.

I would add another significant distinction. Under the modern synthesis, populations are primarily seen as plastic and responsive to changes in the environment, producing species that are most strongly marked by adaptive changes. In the postmodern evolutionary view, history dominates — most of the properties of a species are a contingent product of its ancestors’ attributes. “Everything is the way it is because it got that way.” Everything you see in an organism is a consequence of its history, with the addition of a few unique adaptive fillips, and that has two significant implications: you can’t understand an organism without recognizing the impact of its phylogeny, and the modern form preserves ancestral relationships that can be analyzed to discern that history.

And that, of course, demolishes the bogus distinction between historical and observational science that Ken Ham laughably makes. When I observe a fruit fly or a zebrafish or a human being, I am seeing its history made manifest in its structure. See also John Timmer’s recent post on history and science for more.


Bromham L, Penny D (2003) The modern molecular clock. Nat Rev Genet 4(3):216-24.

Koonin EV (2011) The Logic of Chance: The Nature and Origin of Biological Evolution. FT Press.


*I’m not going to get into the evidence for quasi-Lamarckian evolution here, but I will say that there is good evidence for some of it: Koonin discusses the CRISPR-Cas system of adaptive immunity in bacteria. Maybe some other time I can write that up.

Comments

  1. #2 Robert
    February 14, 2014

    So has the ratio of neutral :: non-neutral mutations remained constant over time?

    Since most non-neutral mutations are not beneficial, I could imagine that mutation which makes a gene more robust against mutations could be beneficial (up to the point that it’s so robust it won’t be able to adapt at all.) This might imply that evolution could have started in some sort of selection theory regime, and then evolved to a more (nearly) neutral theory regime.

  2. #3 Rosie Redfield
    http://rrresearch.fieldofscience.com
    February 14, 2014

    I think the conventional/Lamarckian explanation for CRISPR (favoured by Koonin) is almost certain to be wrong. It’s full of glib assumptions and explanatory holes. (And yes, I need to write a RRResearch post explaining my concerns.)

  3. #4 David Marjanović
    Museum für Naturkunde, Berlin
    February 14, 2014

    I could imagine that mutation which makes a gene more robust against mutations could be beneficial (up to the point that it’s so robust it won’t be able to adapt at all.)

    That would be a beneficial mutation in the gene for a repair enzyme…

    Also, losing the ability to mutate is great as long as the environment is stable. Once that changes, extinction follows.

  4. #6 Brett
    February 14, 2014

    I looked up purifying selection on wikipedia, and it says the removal of harmful alleles that reduce the reproductive fitness of members of a population. Does that happen in response to environmental changes, or is it just that in general they pop up randomly and then disappear?

  5. #7 qetzal
    February 14, 2014

    “[M]ost of the variation found in evolutionary lineages is a product of random genetic drift.”

    It’s clear to me that’s true for genetic variation (at least in eukaryotes). But what about phenotypic variation? How much role does drift play in determining phenotypic differences between species?

    I’m aware of some of Lenski’s findings with E. coli, where evolving the ability to use citrate was apparently contingent on prior fixation of certain mutations that were neutral by themselves. But I’m guessing that overall, the relative contribution of drift to phenotypic change is still an open question, yes?

  6. #8 Richard Bellingham
    February 15, 2014

    That makes sense. Isn’t it the case though that a mutation that happens now and confers no benefit or flaw (thus falling in the netural or nearly neutral area and being fixed in a proportion of the population through chance) might even generations later provide a benefit if the environment changes? For example a change in cell membrane proteins that makes a particular group of organisms in the population immune to a given virus.

  7. #9 David Marjanović
    Museum für Naturkunde, Berlin
    February 15, 2014

    I looked up purifying selection on wikipedia, and it says the removal of harmful alleles that reduce the reproductive fitness of members of a population. Does that happen in response to environmental changes, or is it just that in general they pop up randomly and then disappear?

    I’m not sure what you mean. Mutations always pop up randomly. When they’re harmful in the environment the organism happens to live in, that organism’s descendants will by definition be underrepresented in the next generations, and that’s called purifying selection.

    For example a change in cell membrane proteins that makes a particular group of organisms in the population immune to a given virus.

    Yes, this happens. For an example, see the FtB version of this thread.

  8. #10 Chuck
    February 15, 2014

    In a very broad sense, isn’t still correct to say that phenotypic differences are a consequence of selection pressure? There may be a lot of neutral changes in the background, but doesn’t natural selection still account for what an organism “is”?

  9. #11 G
    February 16, 2014

    In a big-picture way, would it be correct to define evolution as non-directional changes in the heritable characteristics of organisms?

    In which case, can we account for the empirical increase in complexity and diversity of organisms as the outcome of responses to change in the environment?

    Would it be correct to say that the removal of disadvantageous mutations from an organism’s gene pool produces an effect that’s equivalent to increasing the relative prevalence of neutral and positive mutations, even if the rate of disadvantageous mutations is much higher than that of neutral and positive ones?

    And/or, to what do you attribute the increase in complexity and diversity of organisms over time?

    BTW, I too dislike postmodernism as it’s usually applied, but given your caveat, I assumed you were using the term differently to its more common use.

  10. #12 David Marjanović
    Museum für Naturkunde, Berlin
    February 16, 2014

    would it be correct to define evolution as non-directional changes in the heritable characteristics of organisms?

    Evolution = descent with heritable modification. :-)

    the empirical increase in complexity and diversity

    It’s not clear if there’s an empirical increase in diversity, though there probably is. However, by all definitions of “complexity” anyone has tried to test, there has not been an increase in complexity. Most organisms are as simple as they’ve always been; and while parasites predictably become simpler, there’s no comparable factor that would increase complexity.

    Would it be correct to say that the removal of disadvantageous mutations from an organism’s gene pool produces an effect that’s equivalent to increasing the relative prevalence of neutral and positive mutations,

    Yes.

    even if the rate of disadvantageous mutations is much higher than that of neutral and positive ones?

    It isn’t. The vast, vast majority of mutations is neutral or nearly so. That’s an empirical fact, easily understood from such things as junk DNA, synonymous mutations, and the composition of proteins.

    to what do you attribute the increase in […] and diversity of organisms over time?

    Again, be careful in your extrapolations from the fossil record! However, diversity increases when it can increase; there’s nothing to stop it, and making a new ecological niche is a great way to avoid competition.

  11. #13 Chuck
    February 16, 2014

    HTML Generator Sample Page

    "…vast majority of mutations is neutral or nearly so. That’s an empirical fact, easily understood from such things as junk DNA."

    What's the latest on "junk" DNA? Is most of it really neutral or is there the possibility that it is functional in some way that is not yet undestood?

  12. #14 An explorer
    February 17, 2014

    In the 1863 a logger was kidnapped by a female orangutan at Kinabatangan in Borneo and kept as a love toy and had to perform on her to earn his tapioca and banana! After 13 years of sexual captivity he escaped and was very sad and distressed to had to leave all his 3 progeny behind! It is rumoured that they thrived and propogated as per the rare sighting in the deep forest by the natives! It is rumored that The Malaysian Institute of Science is trying to plan an expedition to acquire a “bighand” for study on their theory of inter-species breeding and gmo for a super warrior race!

  13. #15 Michael
    Tampa
    February 17, 2014

    “What’s the latest on “junk” DNA?”

    The latest is simply that there is no such thing as “junk DNA”. Rather, the “junk” can encode what we now recognize as ‘intrinsically disordered proteins’ (IDP), whereby some percentage of disorder must be available to many proteins; in some that percentage is very high, and others very low, but it is safe to say that that every protein is dependent on some level of flexibility that previously-called “junk” DNA more often than not provides. Likewise, “junk” regions by their nature are as evolutionarily conserved as their counterparts and are every bit as necessary. The amount of functionality that IDP provide cannot be understated, as many of the most ordered proteins rely on the ability of IDPs conform to their different interfaces.

  14. #16 Neurokeen
    February 17, 2014

    Chuck:

    Check out Dan Graur et al.’s “On the immortality of television sets: “function” in the human genome according to the evolution-free gospel of ENCODE”. It’s a little over the top in terms of style, but a very good paper discussing definitions (and misused definitions) of junk DNA and functional DNA in the context of the relatively recent ENCODE project.

  15. #17 David Marjanović
    Museum für Naturkunde, Berlin
    February 17, 2014

    It’s a little over the top in terms of style

    It’s not. Really, it’s not.

  16. […] Fruit for Human WGS Why is math research important? The state of modern evolutionary theory may not be what you think it is (I noted several years ago that neutral theory is completely neglected in popular accounts of […]

  17. #19 Reno Hates Me
    United States
    February 18, 2014

    Wow. Thanks for this post. I teach evolution in my Freshmen Biology course but it’s not “my thing” and I know I’m not completely up to date on the topic. I have been teaching genetic drift as part of the discussion but I did not realize how important it seems to be. Time to make some changes to my lecture notes!

  18. #20 Min
    February 19, 2014

    Is the speed of environmental change a factor? That is, with rapid environmental change would we expect to see an increase in advantageous and deleterious mutations and a reduction in neutral and nearly neutral mutations?

    To use the hill-climbing metaphor, once the population has nearly reached the summit, few mutations are advantageous, and many more are deleterious, which keeps the population pretty much near the top, but not at it, with drift as a major factor. But when the environment changes so that the population starts to climb another hill (or out of a valley), more mutations are advantageous and there are a variety of upward paths, so that upward motion does not reduce opportunities to any extent.

    With genetic algorithms and genetic programming, you often see a regime of rapid hill-climbing followed by a long regime of drift. That’s what prompted my question.

  19. #21 Talbert
    February 20, 2014

    “I was rather surprised yesterday to see so much negative reaction to my statement that there’s more to evolution than selection, and that random, not selective, changes dominate our history. ”

    You are surprised because you are an idiot, and a dangerous one at that. You are promoting a generation of biggoted zealots to think of themselves as superior “brights” and to think of everyone with a differing opinion as dangerous, violent, and subhuman scum that needs to have their way of life suppressed and eradicated, by force if necessary as their way of raising children is “child abuse”.
    Militant atheists have already set the stage for horrors to be committed in the name of “secular humanism” in the 21st century.

    PZ, understand when people look back at your work they will not see your worthless comments and pathetic, insignificant insight into evolutionary theory. No, they will see your bigoted remarks on “religion” and even though they were made in a different and more peaceful time they will forever taint you in the eyes of posterity as giving future generations license to commit a new holocaust of the 21st century in the name of “atheism”. You probably think I’m nuts but think about the vitriol you received for merely questioning the official line, the propaganda, of evolutionary theory – realize you are being accused of heresy. I support you and every last comment you have on evolutionary theory, I fucking HATE Intelligent design, but think long and hard about the way you treat the rich variety of human belief systems, how you paint them with one long bigoted brush stroke. The next generation looks at you and your position with respect, think hard about whats coming. Islam is not the threat, it’s the bigoted brights I fear.

  20. #22 David Marjanović
    Museum für Naturkunde, Berlin
    February 20, 2014

    Is the speed of environmental change a factor? That is, with rapid environmental change would we expect to see an increase in advantageous and deleterious mutations and a reduction in neutral and nearly neutral mutations?

    Yes, pretty much as you explained – except that the number of neutral mutations remains overwhelmingly high, because most of them have no effect on the phenotype and are therefore invisible to selection altogether.

    You are promoting a generation of biggoted zealots to think of themselves as superior “brights”

    Ooh, what a beautiful strawman. It burns so bright!

    First, you’re confusing PZ with Richard Dawkins, whose bright idea “Brights” was. Second, even Dawkins has abandoned this nonsense. Third, I doubt Dawkins even noticed he was by implication calling everyone else “dim”; he’s really bad at noticing such things. He naively tried to copy the success of “gay”, not noticing that the situation is way too different for such a copy to be possible.

    to think of everyone with a differing opinion as dangerous, violent, and subhuman scum that needs to have their way of life suppressed and eradicated, by force if necessary as their way of raising children is “child abuse”.

    PZ has spoken out several times against Dawkins’s comparison of religious upbringing to child abuse because it trivializes child abuse. You should read the complete version of Pharyngula, not this biology-only one.

    PZ, understand when people look back at your work they will not see your worthless comments and pathetic, insignificant insight into evolutionary theory.

    …what, do you believe PZ is trying to get famous by explaining the theory of evolution?!?

    He’s trying to educate the public. That’s, y’know, his job as a university teacher. None of the insights in his post are his own, and he doesn’t claim they are, which is why he cites his sources! Clean your glasses once in a while.

    You probably think I’m nuts but think about the vitriol you received for merely questioning the official line, the propaganda, of evolutionary theory – realize you are being accused of heresy.

    :-D :-D :-D :-D :-D :-D :-D :-D :-D :-D :-D :-D

    I don’t even know where to begin! PZ is explaining current textbook wisdom to us, and that’s his whole point, as he has explicitly said several times!

    What are you on about? What have you smoked, and can I get it legally in the Netherlands?!? :-D

  21. #23 Min
    February 20, 2014

    Moi: “Is the speed of environmental change a factor? That is, with rapid environmental change would we expect to see an increase in advantageous and deleterious mutations and a reduction in neutral and nearly neutral mutations?”

    David Marjonović: “Yes, pretty much as you explained – except that the number of neutral mutations remains overwhelmingly high, because most of them have no effect on the phenotype and are therefore invisible to selection altogether.”

    Thank you, David. Very interesting. :)

    Question 2. Does sex have anything to do with this? Does inheriting different alleles from parents tend to make deleterious mutations less deleterious and advantageous mutations less advantageous, thus making them neutral or nearly neutral?

  22. #24 David Marjanović
    Museum für Naturkunde, Berlin
    February 21, 2014

    Depends. Some alleles are dominant (meaning they work even if only one copy is present), others are recessive (their effect only shows if there’s no other allele), yet others are intermediate (half of the effect is present when one copy is present, or something else happens entirely). This depends on the effects of the mutations on the protein level or beyond: an allele that codes for a broken, dysfunctional protein is likely recessive.

    So… mutations that cause recessive alleles are invisible to selection for some time; they only have an effect when two such alleles meet in the same organism. In short, sexual reproduction makes them stay neutral for longer.

    And there’s only one o in my name. :-)

  23. #25 Harald Striepe
    california
    February 22, 2014

    Just a (maybe dumb) question: What role do the old punctuated equilibria play in this?

  24. #26 David Marjanović
    Museum für Naturkunde, Berlin
    February 22, 2014

    They’re an effect, not a cause: an effect of stasis and changes in the environment. They’re not generated internally.

  25. #27 Min
    February 23, 2014

    Thanks again, David. :)

    Sorry for the typo in your name.

  26. #28 Louis
    @biochemistries
    February 24, 2014

    You’ve not really gone into this here, but I’m wondering whether you entirely agree with “Phylogeny: FALSE” in Koonin’s table?

    I’ve written about it on my blog, and no I’m not an entirely knee-jerk skeptic when it comes to pomo, but after looking at both sides I don’t know if the rhizome idea (“forest of trees”) is good, nor to just write off previous work as “largely obsolete” as Koonin and Raoult have (detailed in my post, below). Your opinion (or anyone else’s) on this matter would be great to hear!

    http://biochemistri.es/post/77645400118/postmodern-reassessment-of-some-central

  27. #29 David Marjanović
    Museum für Naturkunde, Berlin
    February 24, 2014

    That figure looks exaggerated to me; but it’s of course true that the tree isn’t 100 % of the story – lateral gene transfer is a thing, and once you get to sexual reproduction, you get incomplete lineage sorting and introgression.

    If you want PZ’s opinion, send him an e-mail; his address is at the complete version of Pharyngula.

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