This article in the Guardian, “Do we need a new theory of evolution?” has it’s moments, but I hated the title and didn’t care at all for the opening. It’s true, scientists don’t know everything, but we know more than the author thinks.

Strange as it sounds, scientists still do not know the answers to some of the most basic questions about how life on Earth evolved. Take eyes, for instance. Where do they come from, exactly? The usual explanation of how we got these stupendously complex organs rests upon the theory of natural selection.

You may recall the gist from school biology lessons. If a creature with poor eyesight happens to produce offspring with slightly better eyesight, thanks to random mutations, then that tiny bit more vision gives them more chance of survival. The longer they survive, the more chance they have to reproduce and pass on the genes that equipped them with slightly better eyesight. Some of their offspring might, in turn, have better eyesight than their parents, making it likelier that they, too, will reproduce. And so on. Generation by generation, over unfathomably long periods of time, tiny advantages add up. Eventually, after a few hundred million years, you have creatures who can see as well as humans, or cats, or owls.

This is the basic story of evolution, as recounted in countless textbooks and pop-science bestsellers. The problem, according to a growing number of scientists, is that it is absurdly crude and misleading.

For one thing, it starts midway through the story, taking for granted the existence of light-sensitive cells, lenses and irises, without explaining where they came from in the first place. Nor does it adequately explain how such delicate and easily disrupted components meshed together to form a single organ. And it isn’t just eyes that the traditional theory struggles with. “The first eye, the first wing, the first placenta. How they emerge. Explaining these is the foundational motivation of evolutionary biology,” says Armin Moczek, a biologist at the University of Indiana. “And yet, we still do not have a good answer. This classic idea of gradual change, one happy accident at a time, has so far fallen flat.”

But we don’t take the existence of light sensitive cells for granted at all! It’s biochemistry. There are organic molecules that can absorb the energy of a photon and undergo a conformational change; there are single-celled organisms that can recognize the impact of light and change their behavior or biochemistry. We don’t need to explain any stepwise change in the properties of abiological materials, because that’s just physics or organic chemistry. Is evolutionary biology incomplete if it doesn’t argue that physics evolved? Are we allowed to understand that chemistry existed long before life?

The article spends a lot of time on the Extended Evolutionary Synthesis, giving it more credibility than it deserves, and plays up the drama of evolutionary theory changing, as if that wasn’t a normal scientific response to new evidence and ideas. Stuff like this doesn’t help.

Then came a devastating series of new findings that called into question the theory’s foundations. These discoveries, which began in the late 60s, came from molecular biologists. While the modern synthesists looked at life as if through a telescope, studying the development of huge populations over immense chunks of time, the molecular biologists looked through a microscope, focusing on individual molecules. And when they looked, they found that natural selection was not the all-powerful force that many had assumed it to be.

They found that the molecules in our cells – and thus the sequences of the genes behind them – were mutating at a very high rate. This was unexpected, but not necessarily a threat to mainstream evolutionary theory. According to the modern synthesis, even if mutations turned out to be common, natural selection would, over time, still be the primary cause of change, preserving the useful mutations and junking the useless ones. But that isn’t what was happening. The genes were changing – that is, evolving – but natural selection wasn’t playing a part. Some genetic changes were being preserved for no reason apart from pure chance. Natural selection seemed to be asleep at the wheel.

Evolutionary biologists were stunned.

“Devastating.” “Stunned.” Nah. There’s an ongoing argument about the relative importance of various processes, but no one was emotionally wrecked by the discovery that evolution is complicated. There are conservative scientists who refuse to budge or even acknowledge the existence of stuff like neutral theory, but they’re not particularly interesting. On the other side, there are wacky extremists with their hair on fire screaming that the existence of developmental plasticity means that we have to throw away everything. Most scientists see new phenomena and say, “Cool. Now how does this fit with that?”

The article links to a Nature article, “Does evolutionary theory need a rethink?”, and it takes an odd angle. It only mentions the EES side, but the Nature article had two sides, one answering the question with “YES, URGENTLY,” the other saying “NO, ALL IS WELL.” So the EES side sets everything up as deeply in opposition to the Standard Evolutionary Theory (SET) side.

In our view, this ‘gene-centric’ focus fails to capture the full gamut of processes that direct evolution. Missing pieces include how physical development influences the generation of variation (developmental bias); how the environment directly shapes organisms’ traits (plasticity); how organisms modify environments (niche construction); and how organisms transmit more than genes across generations (extra-genetic inheritance). For SET, these phenomena are just outcomes of evolution. For the EES, they are also causes.

Valuable insight into the causes of adaptation and the appearance of new traits comes from the field of evolutionary developmental biology (‘evo-devo’). Some of its experimental findings are proving tricky to assimilate into SET. Particularly thorny is the observation that much variation is not random because developmental processes generate certain forms more readily than others. For example, among one group of centipedes, each of the more than 1,000 species has an odd number of leg-bearing segments, because of the mechanisms of segment development.

Maybe I’m an oddball, but nothing there is in conflict. I learned about plasticity, niche construction, and epigenetics and just took them on as part of the process of evolution, working alongside familiar older ideas about changes in allele frequency. How can anyone think evo-devo is some radical competitor to evolutionary theory? It’s got “evolution” in the name! I’ve been following evo-devo for forty years now, and certainly in the early days some were over-enthusiastic, calling it revolutionary, but really, it’s simply part of evolution. I don’t need to chant slogans or demand wild changes in the textbooks, they’ve all been steadily bringing more and more content about these crazy ideas about mechanisms other than selection into the fold. Nusslein-Volhard and Wieschaus are in freshman college biology texts now!

But the EES fanatics are not satisfied.

The case for EES rests on a simple claim: in the past few decades, we have learned many remarkable things about the natural world – and these things should be given space in biology’s core theory. One of the most fascinating recent areas of research is known as plasticity, which has shown that some organisms have the potential to adapt more rapidly and more radically than was once thought. Descriptions of plasticity are startling, bringing to mind the kinds of wild transformations you might expect to find in comic books and science fiction movies.

Yes, plasticity exists, it’s really neat-o, I’ve read lots of papers on it, and I’m a big fan of Mary Jane West-Eberhard’s work. So? What does it mean, “given space in biology’s core theory”? I don’t understand. I open up an evolutionary biology textbook, and it takes hundreds of pages to explain how evolution works, and it includes plasticity, and punctuated equilibrium, and nearly neutral theory, and lots of ideas that explain a complex process. What is this “core theory”? They talk as if there is some tidy concise kernel that everything is derived from, and they want to wedge in some detail. That’s not how it works. That’s not how anything works. Maybe they should step back and explain accurately what this “core theory” is.

The Guardian article sort of redeems itself at the end by pointing out the obvious: what is this single “core theory” they want to modify? There isn’t one!

The computational biologist Eugene Koonin thinks people should get used to theories not fitting together. Unification is a mirage. “In my view there is no – can be no – single theory of evolution,” he told me. “There cannot be a single theory of everything. Even physicists do not have a theory of everything.”

This is true. Physicists agree that the theory of quantum mechanics applies to very tiny particles, and Einstein’s theory of general relativity applies to larger ones. Yet the two theories appear incompatible. Late in life, Einstein hoped to find a way to unify them. He died unsuccessful. In the next few decades, other physicists took up the same task, but progress stalled, and many came to believe it might be impossible. If you ask a physicist today about whether we need a unifying theory, they would probably look at you with puzzlement. What’s the point, they might ask. The field works, the work continues.

I’m not thrilled with bringing physics into the story. Most people don’t understand evolutionary theory, so trying to compare it to another complex field that most people don’t understand (including myself) is not helpful at all. I agree with Koonin on the evolution part, though: there are a lot of messy moving parts to evolution, why even try to claim that it’s all unified in one simple, clear principle? Embrace diversity and complexity. You’ll never get anywhere trying to claim ownership of the “core theory”.

That might be the real issue here. In 1859, one man, Darwin, could say “This is my theory,” (with a little nod to Wallace). In the mid-20th century, a massive mob of scientists could come up with something called the Neo-Darwinian Synthesis, but no one person could lay claim to it. It was too big and sprawling and crossed multiple sub-disciplines. Now a handful of people want credit for some half-assed idea they call the EES…sorry, people, it’s just some more tasty ingredients for the stew, it’s not replacing anything.

But mostly accurate.

In the Index to Creationist Claims, rebutting the claim by Henry Morris that No new species have been observed, it is written:

New species have arisen in historical times. For example:

A new species of mosquito, isolated in London’s Underground, has speciated from Culex pipiens (Byrne and Nichols 1999; Nuttall 1998).

This claim that a new species arose since the London Underground was built has been widely reported.

In 1999, an English researcher named Katharyne Byrne went underground to investigate further. When she compared Underground mosquitoes and compared them to others found in London houses, she learned that they were a distinct subspecies.

After ruling out migration from elsewhere in the continent, Byrne concluded that the London Underground was colonized by mosquitoes a single time, then achieved “reproductive isolation,” or barriers to reproduction with different species, in the subway tunnels.

“In the continent” is the critical phrase here. As it turns out, they didn’t look far enough afield — they needed to look at species in North Africa. The London Underground mosquito has a deeper history than the London Underground!

The northern house mosquito Culex pipiens sensu stricto is one of the most important disease vector mosquitoes in temperate zones across the northern hemisphere, responsible for the emergence of West Nile Virus over the last two decades. It comprises two ecologically distinct forms — an aboveground form, pipiens, diapauses in winter and primarily bites birds, while a belowground form, molestus, thrives year-round in subways, basements and other human-made, belowground habitats, bites mammals, and can even lay eggs without a blood meal. The two forms hybridize in some but not all places, leading to a complex ecological mosaic that complicates predictions of vectorial capacity. Moreover, the origin of the belowground molestus is contentious, with iconic populations from the London Underground subway system being held up by evolutionary biologists as a preeminent example of rapid, in situ, urban adaptation and speciation. We review the recent and historical literature on the origin and ecology of this important mosquito and its enigmatic forms. A synthesis of genetic and ecological studies spanning 100+ years clarifies a striking latitudinal gradient — behaviorally divergent and reproductively isolated forms in northern Europe gradually break down into what appear to be well-mixed, intermediate populations in North Africa. Moreover, a continuous narrative thread dating back to the original description of form molestus in Egypt in 1775 refutes the popular idea that belowground mosquitoes in London evolved in situ from their aboveground counterparts. These enigmatic mosquitoes are more likely derived from populations in the Middle East, where human-biting and other adaptations to human environments may have evolved on the timescale of millennia rather than centuries. We outline several areas for future work and discuss the implications of these patterns for public health and for our understanding of urban adaptation in the Anthropocene.

It’s still evolution, just evolution over millennia rather than less than a century.

If you’re bored and feel like exploring all of life, try the One Zoom explorer. It’s a graphical interface to a collection of data about phylogeny.

It’s interesting and useful at the top level, but as you dig down into the twigs and leaves, it starts to fall apart, lacking in detail. That’s what you’d expect if you’re trying to track about 1.5 million documented species (somewhere over 10 million species total). It does help communicate the diversity and complexity of life, though.

OK, so atheists shouldn’t take credit for a decline in religion, but I think science communicators and educators (which is not synonymous with atheism, I’m sure you know) have accomplished something: the gradual decline of creationism. More people are accepting evolution!

In the early years of this blog, way back in the 2000s, I felt a bit of frustration and despair because when I looked at the surveys, all I saw then was a flat line: less than half the population accepted a well-supported scientific fact, and 40% openly rejected it in favor of nonsense contradicted by all the evidence. And the statistics were flat-lined back into the 1960s, when the surveys began! It was all very discouraging, but also motivated a lot of us to get out there and do public science communication. It seems to have worked.

At least, I think educating the public helped. Another factor is that evolution has also become a tribal marker. If you’re a True Republican, you believe in bullshit and the American way; if you’re a True Democrat, you believe in evolution and science. Part of the reason for the growing disparity is simply growing polarization.

Antievolutionism remains a political force. The Republican party often panders to religious fundamentalism, and attitudes toward evolution are politicized as a result. Miller and his collaborators found that 34% of conservative Republicans accepted evolution in 2019, as compared to 83% of liberal Democrats. There is evidence that the politicization is increasing: in 2009, 54% of Republicans and 64% of Democrats accepted human evolution, but by 2013, the ten-point gap widened to a twenty-four-point gap, according to the Pew Research Center.

That tells me it’s just as important as ever to work to make sure citizens accept evolution for the right reasons. Because that’s what the evidence supports.

Nice image to illustrate a basic cladistic principle. I still get whines from creationists complaining that I said we humans are fish — but that’s just a bigger circle enclosing everyone in this image.

For the Lisowicia book, number 4 of the Extinct series, we wanted to show the reader how we mammals are related to Lisowicia and other synapsids. It was important for us that the reader understood, in a visual way, that once you are in a group, you never leave the group. pic.twitter.com/6uwMXNGxav

— Gabriel N. U. (@SerpenIllus) October 22, 2021

I have no illusions that this will ever sink into the brains of the people who deny it.

Brachyury (Greek for “short tail”) is an important protein in animal development — it’s found in all chordates and is expressed along the midline, and sets up the anterior-posterior axis. It seems to play an essential role in defining tissues along the length of the animal, and many mutations have been found in the gene TBXT for it that cause defects in the spinal cord. In addition to the short tail phenotype it’s named for, different variants affect other regions as well. For instance, you probably know that almost all mammals have precisely 7 cervical vertebrae, but there is a mutation in TBXT that reduces that number to 6.

So, basically, if you want to profoundly muck up the developing vertebrae and spinal cord, mutating TBXT is a way to do it, as long as you don’t mind inducing neural tube defects, like say, spina bifida. It’s a dangerously significant gene to tinker with, and most of the outcomes would not be good. But note — humans and other hominoids have an inherited, ubiquitous spinal cord defect. We don’t have tails, unlike other mammals. Could we be carrying a mutation in our TBXT gene? Could that be what caused all us apes to lose our tails? Maybe we should look and compare our TBXT to that of other animals. Huh, what do you know…we do have a curiously broken TBXT.

A little background first. Eukaryotic genes are broken up into segments called exons alternating with other segments called introns. To make a functional gene product, like Brachyury, the cell has enzymes that cut out the introns from the RNA and splice together the exons. The intronic RNA is then generally allowed to be broken down and recycled. So TBXT has 7 exons, E1, E2, E3, E4, E5, E6, and E7, with intervening introns which must be snipped out and the exons spliced together to make a final, complete RNA, E1-E2-E3-E4-E5-E6-E7, which will be translated to make the Brachyury protein.

Another complication: there are these short bits of selfish DNA called Alus which are scattered throughout the genome. We have over a million Alu elements sprinkled throughout, and usually they do nothing, although if an Alu gets inserted into an exon of a gene, it can disrupt the function of that gene. The good news: there is no Alu stuck in the exons of TBXT. There are a couple of them in the introns of TBXT, but remember, the introns get chopped out and thrown away, so they shouldn’t matter. Except that in this case, they do.

In us hominoids, there is one Alu, AluSx1, in intron 5. There is another Alu, AluY, in intron 6. They happen to complement each other in reverse, so in the TBXT RNA, before the introns are edited out, the RNA folds over to make a loop that allows the two Alus to bind to each other. This messes up the editing, because the cell then snips out the introns and the loop, throwing away exon 6. Uh-oh. That means that instead of producing the full length TBXT, we make a shortened version lacking exon 6, called TBXT-Δexon6.

This observation was tested with a couple of nifty experiments. First question: is it really the Alus that are causing this error in splicing? Yes. Doing a little gene editing and knocking out either Alu in human embryonic stem cells causes them to generate full length TBXT transcripts. These are just single cells in a dish, and while you might be curious to know if deleting those specific Alus in a human embryo would lead to it developing a tail, that would be unethical. In a sense, you’d be generating a neural tube defect, never a desired outcome, and we don’t know what other compensatory or cooperative genes to our, for us, normal TBXT-Δexon6 exist.

But hey, good news, we don’t have the same ethical restrictions when working with mouse embryos! Let’s dive into the mouse genome and insert Alus, just like ours, into the introns of the mouse TBXT gene! And so it was done, producing mice that made TBXT-Δexon6, and lo, they had little stumpy tails, or no tails at all.

There are a few complications. Mice that were homozygous for TBXT-Δexon6 died embryonically with substantial neural tube defects. Heterozygotes for TBXT-Δexon6 survived, and exhibited the tailless phenotype with variable penetrance, that is some mice were lacking the whole shebang, missing sacral vertebrae (sv) and all caudal vertebrae (cv), and others lost variable numbers of caudal vertebrae.

It’s lovely work, but I still have to disagree a little bit with their interpretation. Their model of hominoid evolution puts the tail-loss mutation right at the base of the progression.

That’s too simple. The lethality of the homozygous mutant in mice, while we homozygous mutants are fine, tells me that there are a lot of other genes that work together with TBXT to make a viable embryo — that we have a suite of supporting genes that can compensate for the lethal effects of TBXT-Δexon6. This model assumes that all those supporting roles evolved after the TBXT-Δexon6 mutation occurred. There is no reason to think that. Why not consider that our ancestral hominoid had a few exaptations that made it slightly more fault-tolerant in axis formation? Put those additional mutations ahead of the AluY insertion. Then have additional mutations afterwards. Our ancestors were not mice, so there’s no reason to think they’d have had the same response (that is, the lethality) to TBXT-Δexon6 as do modern mice.

Also, now I’m really interested in those additional mutations. TBXT isn’t the whole story.

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Xia, b, Zhang W, Wudzinska A, Huang E, Brosh R, Pour M, Miller A, Dasen JS, Maurano MT, Kim SY, Boeke JD, Yanai I (2021) The genetic basis of tail-loss evolution in humans and apes. https://www.biorxiv.org/content/10.1101/2021.09.14.460388v1