François Jacob has died

Jacob and Jacques Monod, who won the Nobel Prize in 1965 for their work on the lac operon, were the fellows who really put gene regulation on the map, working out the mechanisms behind switching genes off and on in response to environmental cues. I always talk about their work on day one of my developmental biology courses; everything else in molecular genetics and development are built on the foundation they laid down.

And now Le prix Nobel et résistant François Jacob est mort (Monod died in 1976).

By the way, in addition to being a great scientist, Jacob was also a great atheist. This is a loss to all of us.

Carl Zimmer has written a lovely tribute to Jacob’s work.

Coelacanths are unexceptional products of evolution

The coelacanth genome has been sequenced, which is good news all around…except that I found a few of the comments in the article announcing it disconcerting. They keep calling it a “living fossil” — and you know what I think of that term — and they keep referring to it as evolving slowly

The slowly evolving coelacanth

The morphological resemblance of the modern coelacanth to its fossil ancestors has resulted in it being nicknamed ‘the living fossil’. This invites the question of whether the genome of the coelacanth is as slowly evolving as its outward appearance suggests. Earlier work showed that a few gene families, such as Hox and protocadherins, have comparatively slower protein-coding evolution in coelacanth than in other vertebrate lineages.

Honestly, that’s just weird. How can you say its outward appearance suggests it is slowly evolving? The two modern species are remnants of a diverse group — it looks different than forms found in the fossil record.

And then for a real WTF? moment, there’s this from Nature’s News section.

It is impossible to say for sure, but the slow rate of coelacanth evolution could be due to a lack of natural-selection pressure, Lindblad-Toh says. Modern coelacanths, like their ancestors, “live far down in the ocean, where life is pretty stable”, she says. “We can hypothesize that there has been very little reason to change.” And it is possible that the slow genetic change explains why the fish show such a striking resemblance to their fossilized ancestors.

Snorble-garble-ptang-ptang-CLUNK. Reset. Does not compute. Must recalibrate brain.

None of that makes sense. The modern fish do not show a “striking resemblance” to their fossilize ancestors — they retain skeletal elements that link them to a clade thought to be extinct. This assumption that Actinistian infraclass has been unchanging undermines their conclusions — the modern species are different enough that they’ve been placed in a unique genus not shared with any fossil form.

Then the argument that they must live in a stable environment with a lack of natural-selection pressure is absurd. Selection is generally a conservative process: removing selection pressures from a population should lead to an increase in the accumulation of variability. Do they mean there has been increased selection in a very narrowly delimited but stable environment?

But even that makes no sense. We should still be seeing the accumulation of neutral alleles. Increased selection is only going to remove variability in functional elements, and most of the genome isn’t. I suppose one alternative to explain slow molecular evolution would be extremely high fidelity replication, but even that would require specific selection constraints to evolve.

This article broke my poor brain. I couldn’t see how any of this could work — it ignored the fossil evidence and also seemed to be in defiance of evolutionary theory. It left me so confused.

Fortunately, though, the journal BioEssays came to my rescue with an excellent review of this and past efforts to shoehorn coelacanths into the “living fossil” fantasy, and that also explained the molecular data. And it does it plainly and clearly! It’s titled, “Why coelacanths are not ‘living fossils’”, and you can’t get much plainer and clearer than that.

First, let’s dismiss that myth of the unchanging Actinistian. Here’s a phylogeny of the coelacanth-like fossils and their one surviving species.

coelacanth_fossils
Comparison of extant and selected extinct actinistians, commonly known as coelacanths. A phylogeny of Actinistia; schematic sketches of body outlines and approximate body length (given in metre) illustrate the morphological diversity of extinct coelacanths: some had a short, round body (Hadronector), some had a long, slender body (Rebellatrix), some were eel-like (Holopterygius) whereas others resembled trout (Rhabdoderma), or even piranha (Allenypterus). Note that the body shape of Latimeria chalumnae differs significantly from that of its closest relative, Macropoma lewesiensis.

Love it. I’ve been looking for a diagram like this for a long time; creationists often trot out this claim that coelacanths haven’t changed in hundreds of millions of years, and there you can see — divergence and variation and evolution, for hundreds of millions of years.

In addition, we can look in more detail at the skull and limbs of these animals. This drawing is comparing modern Latimeria with its closest fossil relative, and even here there are dramatic differences in structure.

actinistian_bones

Comparison of the skeleton of extant and selected extinct coelacanths. A–D: Latimeria and its sister group Macropoma show numerous skeletal differences. A, B: Overall view of the skeletal organisation of the extant coelacanth and of its closest relative. A: Latimeria chalumnae. B: Macropoma lewesiensis. Relative to the body length, in L. chalumnae the vertebrae are smaller, the truncal region of the vertebral column is longer and the post anal region is shorter than in M. lewesiensis. In the latter region, the hemal arches (ventral spines) extend more ventrally in M. lewesiensis than in L. chalumnae. In addition, the swim bladder is ossified in Macropoma but not in Latimeria, and the basal bone of the first dorsal fin is characteristic of each genus. C, D: Comparison of the skulls of L. chalumnae and M. lewesiensis. C: In L. chalumnae, the mouth opens upward, the articular bone (yellow) is long and narrow, the parietonasal shield (red) is short, the premaxillary bone (orange) is devoid of denticle ornamentation, the dorsal part of the cleithum (light brown) is spiny, and the scapulocoracoid (green) is located on the ventral side. D: In contrast, in M. Lewesiensis, the mouth opens forward, the angular bone (yellow) is triangular, the parieto-nasal shield (red) is long, the premaxillary (orange) protrudes and forms a hemispherical snout which is ornamented with prominent denticles, the dorsal part of the cleithrum (light brown) is thick, and the scapulocoracoid, (green) is located more medially. Modified from [3]. E: Pectoral fin skeleton of L. chalumnae (above) and Shoshonia arctopteryx (below). The three first preaxial radials are numbered from proximal to distal. In L. chalumnae the fin appears nearly symmetrical because radial bones (orange) are arranged nearly symmetrically about the fin axis. The proximal preaxial radials 1-2 are extremely short and bear no fin ray, and the preaxial radial 3 is short and fractionated. In contrast, in S. arctopteryx the fin is strongly asymmetrical chiefly because proximal preaxial radials are long and all bear fin rays.

The authors make it clear that this idea of morphological conservation of the Actinistians is simply bogus.

In addition, an examination of the skeleton of the fossil genus Macropoma (approximately 70 Ma), the sister group of Latimeria and the only known fossil actinistian record from the Cretaceous to the present, shows some interesting differences. Not only are the extant coelacanths three times larger than their closest extinct relatives (about one and a half metres vs. half a metre), but there are also numerous structural differences. The swim bladder is ossified in Macropoma but filled with oil in Latimeria, indicating they were probably found in different types of environments. There are also noticeable differences in the vertebral column (the post anal region is shorter and ventral spines extend less ventrally in M. Lewesiensis compared with L. chalumnae), and in the attachment bones of the fins. In addition, Macropoma and Latimeria have distinctly dissimilar skull anatomies, resulting in noticeable differences in head morphology.

Finally, it should not be forgotten that external morphological resemblances can be based on a very different internal anatomical organisation. The most often emphasised resemblance between coelacanths is that they all have four fleshy-lobed-fins. Until recently, the anatomy of the lobed fins of coelacanths was only known in Latimeria, in which the pectoral fin endoskeleton is short and symmetrical. In 2007, Friedman et al. described the endoskeleton of the pectoral fin of Shoshonia arctopteryx, a coelacanth species from the mid Devonian, and therefore contemporary with Miguashaia. They showed that this earliest known coelacanth fin endoskeleton is highly asymmetrical, a characteristic that is probably ancestral since it resembles the condition found in early sarcopterygians such as Eusthenopteron, Rhizodopsis or Gogonasus. This result is additional support, if needed, that extant coelacanths have not remained morphologically static since the Devonian.

Well, so, you may be wondering, what about the molecular/genomic data? Doesn’t that clearly show that they’ve had a reduced substitution rate? No, it turns out that that isn’t the case. Some genes seem to be more conserved, but others show an expected amount of variation.

However, a closer look at the data challenges this interpretation [of slow evolution]: depending on the analysed sequence, the coelacanth branch is not systematically shorter than the branches leading to other species. In addition, most phylogenetic analyses – including analysis of Hox sequences – do not support the hypothesis that the Latimeria genome is slow evolving, i.e. they do not place coelacanth sequences on short branches nor do they detect low substitution rates. The clearest example, which involves the largest number of genes, is a phylogeny based study of forty-four nuclear genes that does not show a dramatic decrease, if any, in the rate of molecular evolution in the coelacanth lineage. What we know about the biology of coelacanths does not suggest any obvious reason why the coelacanth genome should be evolving particularly slowly.

So why is this claim persisting in the literature? The authors of the BioEssays article made an interesting, and troubling analysis: it depends on the authors’ theoretical priors. They examined 12 relevant papers on coelacanth genes published since 2010, and discovered a correlation: if the paper uncritically assumed the “living fossil” hypothesis (which I’ve told you is bunk), the results in 4 out of 5 cases concluded that the genome was “slowly evolving”; in 7 out of 7 cases in which the work was critical of the “living fossil” hypothesis or did not even acknowledge it, they found that coelacanth genes were evolving at a perfectly ordinary rate.

Research does not occur in a theoretical vacuum. Still, it’s disturbing that somehow authors with an ill-formed hypothetical framework were able to do their research without noting data that contradicted their ideas.

Maybe a start to correcting this particular instance of a problem is to throw out the bad ideas that are leading people astray. The authors strongly urge us to purge this garbage from our thinking.

Latimeria was first labelled as a ‘living fossil’ because the fossil genera were known before the extant species was discovered, and erroneous biological interpretations have grown and reports still show little morphological and molecular evolution. A closer look at the available molecular and morphological data has allowed us to show that most of the available studies do not show low substitution rates in the Latimeria genome, and furthermore, as pointed out by Forey [3] long before us, the supposed morphological stability of coelacanths from the Devonian until the present is not based on real data. As a consequence, the idea that the coelacanth is a biological ‘living fossil’ is a long held but false belief which should not bias the interpretation of molecular data in extant Latimeria populations. The same reasoning could be generalised to other extant species (such as hagfish, lamprey, shark, lungfish and tatuara, to cite few examples of vertebrates) that for various reasons are often presented as ‘ancient’, ‘primitive’, or ‘ancestral’ even if a lot of recent data has shown that they have many derived traits [58–64]. We hope that this review will contribute to dispelling the myth of the coelacanth as a ‘living fossil’ and help biologists keep in mind that actual fossils are dead.

But of course we also shouldn’t let that color our data. If analyses showed a significantly reduced substitution rate in the evolution of a species, it ought to get published. If nothing else, it would be an interesting problem for evolutionary theory. Coelacanths, though, don’t represent that problem.

Amemiya CT, Alföldi J, Lee AP, Fan S, Philippe H, Maccallum I, Braasch I, Manousaki T, Schneider I, Rohner N, Organ C, Chalopin D, Smith JJ, Robinson M, Dorrington RA, Gerdol M, Aken B, Biscotti MA, Barucca M, Baurain D, Berlin AM, Blatch GL, Buonocore F, Burmester T, Campbell MS, Canapa A, Cannon JP, Christoffels A, De Moro G, Edkins AL, Fan L, Fausto AM, Feiner N, Forconi M, Gamieldien J, Gnerre S, Gnirke A, Goldstone JV, Haerty W, Hahn ME, Hesse U, Hoffmann S, Johnson J, Karchner SI, Kuraku S, Lara M, Levin JZ, Litman GW, Mauceli E, Miyake T, Mueller MG, Nelson DR, Nitsche A, Olmo E, Ota T, Pallavicini A, Panji S, Picone B, Ponting CP, Prohaska SJ, Przybylski D, Saha NR, Ravi V, Ribeiro FJ, Sauka-Spengler T, Scapigliati G, Searle SM, Sharpe T, Simakov O, Stadler PF, Stegeman JJ, Sumiyama K, Tabbaa D, Tafer H, Turner-Maier J, van Heusden P, White S, Williams L, Yandell M, Brinkmann H, Volff JN, Tabin CJ, Shubin N, Schartl M, Jaffe DB, Postlethwait JH, Venkatesh B, Di Palma F, Lander ES, Meyer A, Lindblad-Toh K. (2013) The African coelacanth genome provides insights into tetrapod evolution. Nature 496(7445):311-316.

Casane D, Laurenti P (2013) Why coelacanths are not ‘living fossils’: A review of molecular and morphological data. Bioessays 35: 332–338.

Larry Moran beat me to it!

Oh god yes yes

Oliver Knevitt has compiled his Top 5 Most Irritating Terms In Evolution Reporting. Read it, science journalists! They are:

  1. “Survival of the fittest.” Up yours, Herbert Spencer!

  2. “Living fossil.” What does that even mean? Do you really think modern coelacanths look anything like the ones from 100 million years ago?

  3. “Missing link.” It assumes a chain, and implies it’s broken. And worse, it’s always getting used when a scientist discovers a new transitional form!

  4. “More evolved/less evolved.” Darwin himself rejected this view, and it’s also one that makes no sense. A clam is as “evolved” as I am.

  5. “Adaptation.” Ooh, interesting choice. Adaptation is real and important, but journalists do tend to overuse it and apply it inappropriately. There are people who’d call male impotence an adaptation.

I’d add “Darwinism”. We aren’t using Darwin’s model anymore; he had no accurate notion of how inheritance worked, for instance — genes and alleles, the stuff of most modern theory, are not present anywhere in his works.

“Darwinian” is also problematic. It does have a specific, technical meaning, but it’s often applied thoughtlessly to every process in evolution.

Let’s also add the usual yellow journalistic trait of turning everything into a “revolution” or a complete disproof of all that has gone before. Asking the question, “Was Darwin Wrong?” is stupid and misleading. Claiming that evo-devo or epigenetics or genomics or molecular biology will completely “revolutionize” or overturn antiquated notions or throw the entire field of evolutionary biology into complete chaos are also nonsense — so far those sub-disciplines have reinforced and modified appropriately an understanding of evolution that was forged in the 1930s. If something really revolutionary comes up, you’ll know it because the mobs of excited scientists flocking to the new idea and turning it into significant advances in our understanding will make it obvious.

No more Dan Markingsons

A few weeks ago I gave a talk in Seattle in which I pointed out that science is not sufficient to define moral behavior. A substantial part of that talk was a catalog of atrocities, such as the Tuskegee syphilis experiment. I said that in purely scientific terms, that was a good experiment; if the subjects had been mice, for instance, setting aside an untreated control group to study the progression of the disease would have been considered an essential part of smart experimental design. One could still argue that the needs of the many outweigh the needs of the few…if one were willing to distance oneself from the humanity of the subjects.

Yes, one can always retreat to the excuse that these were cases of bad science, where the scientists violated the rules of their own profession. But where do the ethical guidelines come from? Not science.

Dan_Markingson

I missed a trick, though. I talked mainly about old cases, when there’s a clear case of the conflict between ethics and science playing out right now, right at my home university: the case of Dan Markingson, the young man who was enrolled in an experimental pharmaceutical study and kept there, even as his mental illness worsened, and who eventually committed suicide.

There’s a new article by a bioethicist on this case.

markingson2

The research abuse in this case is so stunning that when I first learned about it I could scarcely imagine it happening anywhere, much less at the university where I work. In late 2003, psychiatric researchers at the University of Minnesota recruited a mentally ill young man named Dan Markingson into a profitable, industry-funded research study of antipsychotic drugs. The researchers signed him up over the objections of his mother, Mary Weiss, who did not want him in the study, and despite the fact that he could not give proper informed consent. Dan was acutely psychotic, plagued by delusions about demons, and he had repeatedly been judged incapable of making his own medical decisions. Even worse, he had been placed under an involuntary commitment order that legally compelled him to obey the recommendations of the psychiatrist who recruited him into the study.

For months, Mary tried desperately to get Dan out of the study, warning that he was getting worse and that he was in danger of committing suicide. But her warnings were ignored. On April 23, 2004, she left a voice message with the study coordinator, asking, “Do we have to wait for him to kill himself or someone else before anyone does anything?” Three weeks later, Dan committed suicide in the most violent way imaginable. His body was discovered in the shower of a halfway house, his throat slit so severely that he was nearly decapitated, along with a note that said, “I went through this experience smiling.”

You know, I’ve been impressed with my university on many occasions: their commitment to academic freedom has been exemplary, my interactions with the university’s lawyers (I’ve had a few of them…) has always left me satisfied that they are fair and pragmatic. But this is a failure not just of the scientists involved, but the administration of the university. It’s an embarrassment.

Yet for three years the University of Minnesota has managed to bluster and stonewall its way through all the criticism, insisting that it has already been exonerated. Even when the state Legislature passed “Dan’s Law” in 2009, banning psychiatrists from recruiting mentally ill patients under an involuntary commitment order into drug studies, the university continued to insist it had done nothing wrong.

I suspect that the stonewalling is out of fear of opening the door to legal action against a university that is already struggling with constantly dwindling support from the legislature. But it’s necessary that they confront this issue and deal with it honestly — it’s the only way to restore confidence with UM’s ethical culture, and it’s the only way to make sure there are no future Dan Markingsons.

And it’s that last bit that is the important concern.

Mary’s Monday Metazoan: Ol’ Three-Eyes

It’s a frog tadpole with an eye surgically grafted to its trunk!

ol3eyes

Wait, this is an old story — similar experiments were done at least 20 years ago. You can transplant developing eyes to the tadpole, but the cool thing is that the donor optic nerves will grow into the sensory tracts of the dorsal spinal cord and grow anteriorly to the optic tectum, where they will make functional connections. Not, as I recall, adequate for image formation, but at least good enough that the tadpole will startle if a light is flashed at the eye in its tail.

I did kind of go “ugh” at the spin the story put on it, though: that it could lead to a medical breakthrough that would allow blind people to see! Nope. Frogs already readily accept eye grafts and regrow the connections; there are lots of experiments where, for instance, you cut out the adult frog eye, severing the optic nerve, and reinsert it upside down, and the nerves grow back and build new, functional connections. That’s the hard part, getting operational regrowth. Planting ectopic eyes is trivial.

More lies from the Discovery Institute

Oh, christ. Another book is coming from those frauds at the DI, Darwin’s Doubt: The Explosive Origin of Animal Life and the Case for Intelligent Design. It’s Stephen Meyer’s unqualified, incompetent take on the Cambrian explosion.

Casey Luskin has already given us three reasons we’re supposed to buy it. 1) It’s going to contain the best arguments for intelligent design creationism EVAR; 2) it’s going to be packed full of reviews of the work of the “ID research community”; and 3) we’re living in a “post-Darwinian world”, where all the evolutionary biologists are already deserting the sinking ship of neo-Darwinism. Those aren’t reasons to buy the book; those are reasons the book is going to be total crap.

And why should you read it anyway? You want to know about the Cambrian, read books by real scientists. They’re out there already. One excellent resource is James Valentine’s On the Origin of Phyla; it is not light reading, but if you want to know about the paleontology and systematics of the invertebrate phyla of the Ediacaran and Cambrian, it really is the book to read.

And then to my surprise, while I was digging up the link to that book, I discovered that Douglas Erwin and James Valentine have a new book out as of January: The Cambrian Explosion: The Construction of Animal Biodiversity, which the reviews say is less technical than the Phyla text, but highly rated as an excellent overview. I can’t say I’ve read it yet, but I instantly ordered it.

I think it might be an interesting summer project to compare Erwin & Valentine side-by-side with Meyer. Well, “interesting” in a Bambi Meets Godzilla sort of amusing sense.

But if you want to know what caused the Cambrian explosion, I can give you the short answer. Not intelligent design; that doesn’t even make sense. What it was was environmental changes, in particular the bioturbation revolution caused by the evolution of worms that released buried nutrients, and the steadily increasing oxygen content of the atmosphere that allowed those nutrients to fuel growth; ecological competition, or a kind of arms race, that gave a distinct selective advantage to novelties that allowed species to occupy new niches; and the evolution of developmental mechanisms that enabled multicellular organisms to generate new morphotypes readily. Read the real books if you want to know more, and ignore the uninformed babble the charlatans of the DI will try to sell you.

By the way, Joe Felsenstein is asking for help: he’d like suggestions for what Stephen Meyer ought to have in his book.