The Adaptive Ratchet to Irreversibility

A new paper [1] published in Nature experimentally explores the mechanisms that may generally underpin Dollo's law. With a flurry of recent papers, which exclusively rely on phylogenetic approaches (often demonstrably flawed) to challenge one of the soundest principles of character evolution [2], this original approach to an age-old problem is a stand-out.

The group, led by Joe Thornton at the University of Oregon, previously dissected the genetic basis of a shift in function of the glucocorticoid receptor (a DNA transcription factor), using statistical phylogenetics, functional assays, and X-ray crystallography [3]. They found that a once-promiscuous binding receptor--activated by aldosterone, deoxycorticosterone, and to the lesser extent, cortisol--in the common ancestor of jawed vertebrates, became highly cortisol-specific in the lineage leading to ray-finned fishes and tetrapods.

The key substitutions took place in the receptor ligand-binding domain, with two changes necessary and sufficient to shift preference, and several other changes that restrict receptor sensitivity further and stabilize its structure [3]. The experimental reversal of these same changes in the derived receptor surprisingly renders it useless. It cannot activate transcription in the presence of any ligand. In other words, the forward changes cannot be reversed through the same direct path, because it is unsuccessful in the derived background.

Bridgham and colleagues have now identified the group of mutations that comprise this background, the order in which the groups of changes would have to proceed for a reversal of function to take place, and reveal the underlying mechanism.

The initial sequence of mutations fixed in ligand preference switching is largely unconstrained. Any number of them could improve cortisol binding. However, once a particular evolutionary path is taken, it is unlikely that selection can replay the highly specific sequence of events to revert to the ancestral state.

The process is akin to an evolutionary ratchet, making the receptor intolerant of ancestral features present immediately preceding the present form.

The paper convincingly shows that the initial stages of the reversal must follow a very particular sequence, as well as take steps that do not yield a measurable advantage in either the derived or ancestral function. The reversal paths would thus have to pass through adaptive troughs, even if the selective environment favored the ancestral form. Paraphrasing Günther Wagner in the accompanying news commentary, the receptor's path effectively burns bridges that it just went over, thus making the reverse path exceedingly implausible.

[1] Bridgham, J. T., Ortlund, E. A. & J. W. Thornton. 2006. An epistatic ratchet constrains the direction of glucocorticoid receptor evolution. Nature 461, 515-519.

[2] Gould, S. J. 1970. Dollo on Dollo's law: irreversibility and the status of evolutionary laws. J. Hist. Biol. 3:189–212.

[3] Bridgham, J. T., Carroll, S. M. & J. W. Thornton. 2006. Evolution of hormone-receptor complexity by molecular exploitation. Science 312: 97–101; Ortlund, E. A., Bridgham, J. T., Redinbo, M. R. & J. W. Thornton. 2007. Crystal structure of an ancient protein: evolution by conformational epistasis. Science 317:1544–1548.

A New Holiday

Apparently, today is the First Annual Postdoc Appreciation day. Events have been planned around the country (and Canada and Australia). If you don't see one in your area, perhaps take your postdoc(s) out for a beer at least.

Echidnas, duckbills, and evolutionary rates

I just returned from a two-month trip to Australia, where – for all you twitchers out there – I had a ‘clean sweep’ of Australia’s living monotremes: the platypus and the short-beaked echidna. These are truly bizarre mammals: in addition to obvious modifications of their trophic morphology (duck-bills and “beaks”), they lay eggs and possess a cloaca (on that last subject, we can all be thankful that it was the therian lineage that gave rise to modern humans). Given the phylogenetic and phenotypic distinctiveness of these strange beasts, it is hard to avoid viewing monotremes as “living fossils”, characterized by a long history of low but stable diversity and minimal morphological change. But in this week’s early edition of PNAS, Phillips et al. make the curious claim that terrestrial echidnas are recently derived from aquatic or semi-aquatic ancestors.

The evidence in Phillips et al. hinges on a reinterpretation of the fossil record in conjunction with molecular clock analyses of the echidna-platypus split. Knowing nothing about the cranio-mandibular morphology of monotremes, I am in no position to evaluate much of this work. Still, I found this to be a plausible conclusion and one that seems to make sense: under the new date for the platypus-echidna split (~32 Ma), rates of molecular evolution on both the stem monotreme and subsequent branches are well within the distribution of rates seen in other vertebrates. If, however, the split occurred at least 112.5 Ma, as was proposed previously by Rowe et al. , rates on the monotreme stem would be among the highest reported for vertebrates, and rates after the split would be among the slowest! If Phillips et al. are correct, this is a fascinating bit of natural and evolutionary history. Despite the grumbling of a small but vociferous group of aquatic ape enthusiasts , there are very few well-supported cases of secondarily derived terrestriality from aquatic/semi-aquatic ancestors. So finding that a proto-platypus ecomorph gave rise to Australia’s famous ant-loving “porcupine” is an interesting one indeed.

I think this work challenges some of our assumptions about old, species-poor lineages. Often, such groups are described as “living fossils.” Groups like coelacanths, lungfishes, tuataras, bowfins, and more have persisted for hundreds of millions of years with what appear to be very slow rates of diversification and morphological evolution. Paleontologists have even used the word “inert” to describe the nature of evolution in groups like these. But here we have what appears to be a major adaptive transition between fundamentally different morphologies in one of these living fossil lineages. Why has this group undergone such a radical ecological shift? And conversely, why do so many other groups seem to be inert?

Snake with a Foot?

The Telegraph ran a piece two days ago about the discovery of a snake with a foot in China, including a photo of the animal. Although the photo is too poorly done to permit a real scientific evaluation, a few red flags suggest a possible alternative explanation - that the foot belongs to a prey item. First, the snake's body is obviously bulged in the vicinity of the foot indicating the snake likely just ingested a large prey item. Second, the foot is facing backwards - the direction we'd expect given the snakes tend to consume their prey head first. Third, the foot is really an entire limb complete with digits: although elegant developmental studies have shown that snakes are capable of producing rudimentary limbs, they don't produce the sort of fully formed feature we see in this photo. The Telegraph article suggests that the snake is being studied by the Life Sciences Department at China's West Normal University in Nanchang. My guess is that this study came to an abrupt end when they cut the snake open and found a partially digested lizard in its belly.

Given the quality of the evidence, this story has gotten far more attention than it deserves (1, 2, 3).

UPDATE: I'm not the first to propose that this limb is from a prey item. Comments at Pharyngula suggested the same explanation earlier today.

More on Patents

This is a partial transcript from J.E.M. Supply v. Pioneer Hi-Bred International (U.S. Supreme Court, 1996)

Justice Souter: [A previous case,] Chakrabarty probably should have come out the other way because you had a specific statute, the PPA [Plant Protection Act], which covered this asexually reproducing plant, a bacterium, and yet the Court did not say that the coverage of [patent law section] 101 was thereby defeated.
Attorney: I don't believe that the Chakrabarty Court viewed the bacterium as a plant.
Justice Souter: Well, what else could it view it as? I mean, [...] I wasn't sure myself, and I went to the dictionary, and the dictionary says it's a plant.
Attorney: --I... the Chakrabarty Court spoke of it as a microorganism.
Justice Souter: Which is a generic term. [...] I take it then on... on your position, if we assume that the bacterium is a plant and it asexually reproduces, the decision in Chakrabarty should have been that it's covered by the PPA and there's no 101 patent.

***

One of our previous post topics (inspired by Elizabeth Pennisi's Science news article), on Microsoft's attempt to patent some commonly used phylogenetic methods, spurred some unlikely side reading. Sidelined by an injury, I picked up Robert B. Laughlin's excellent book on excesses of patenting, The Crime of Reason, and perused some entertaining law texts.

Pennisi cites an obviously frustrated Bill Piel whose comment: "Microsoft might as well patent the multiplication tables," is funnier still because they tried something very similar. Microsoft previously tried to patent verb conjugation! (Patent App# 20060195313, Voetberg et al. 08/31/2006; cannot be accessed online.)

It seems to be very important in biology-related lawsuits whether or not some process, method, etc., can receive protection under patent law section 101. While the U.S. Supreme Court decisions state that, "An algorithm, or mathematical formula, is like a law of nature, which cannot be subject to a patent." But section 101 of the patent law reads, "Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefore, subject to the conditions and requirements of this title." Additionally, section 100 defines process as, "process, art, or method, and includes a new use of a known process, machine, manufacture, composition of matter, or material."

The interpretation of these laws and statutes is ultimately up to the Patent Office and the courts. Both have erred in the past, and judging by the above-cited patently pedestrian exchange in the U.S. Supreme Court over the case involving my two favorite topics, phylogenetics and plant sex, I am not optimistic.

Butterfly Sex and Wild Science: The Curious Tale of Caterpillars and Velvet Worms

Lots of people have peculiar ideas. For example, belief in the Loch Ness monster, alien abduction, and the chupacabra, are widespread. However, most rational scientists don’t expect that their as yet unsupported wild notion will find its way into the pages of a highly prestigious international scientific journal. In fact, many of us are conscious or unconscious adherents to the concept (popularized by Carl Sagan, but perhaps traceable to something called ‘Hume’s maxim’) that “Extraordinary claims require extraordinary evidence.” Or if not extraordinary evidence, at least some evidence. . . . right?

Not so in the pages of the latest issue of the Proceedings of the National Academy of Sciences (PNAS) in which Donald Williamson has recently published his notion that the larval stage of lepidopterans (known to most of us as the caterpillar), arose as a consequence of hybridization between insects and the Burgess Shale living fossil onychophorans (aka. velvet worms, see previous blog post). Although this hypothesis would be very interesting if found to be true, the author provides us with absolutely no evidence to support his claim (aside from observing the superficial similarity between adult velvet worms and larval moths and butterflies, which he illustrates in some very poorly reproduced line drawings that really need to be seen to be believed).

Discussed extensively by Jerry Coyne in his blog post entitled “Worst paper of the year?”, this article has already received more press attention (most of it, unfortunately, negative) than many of us will receive in our lifetimes. Of particular note was a lengthy article on the paper published in “Scientific American” which unflatteringly likens PNAS to the “National Enquirer,” although the analogy might be better suited to the “Weekly World News,” a more frequent purveyor of stories on strange hybrids (such as this gem on a purported goldfish–piranha cross). Much of both Coyne’s blog entry and Scientific American article focus on the very undemocratic review process in place at PNAS that is unique among high-tiered scientific journals in the U. S. At PNAS, candidate articles can be submitted to the journal directly and subject to normal scientific peer review (a process known as “direct submission”), or they can be “communicated” by a National Academy member. In the case of communicated submissions, the communicating member selects referees to review the submitted manuscript. For Williamson’s paper the communicating NAS member was Lynn Margulis, most famous for her revolutionary but now widely accepted theory for the endosymbiotic origin of mitochondria in eukaryotes. (As a point of irony with regard to the Sagan quote, above, Margulis is also a former wife of Carl Sagan.) Margulis admits in the “Scientific American” article that it took six or seven reviews to find the “‘2 or 3’ necessary to make a case for its publication” and is described as having a “fondness for weird theories.”

Scorn has been ladled on a review process that is designed this way (notably, here), but does it also have some merit if it allows the seasoned and respected scientists that mostly compose the National Academy a means of facilitating the publication of potentially revolutionary ideas that might otherwise never land in such a prestigious journal? The Williamson article seems to provide evidence that this merit comes at a cost, but then there’s no such thing as a free lunch is there?

A Velvet Worm!

What better way to celebrate the 100 year anniversary of the Burgess Shale's discovery than by finding one the coolest surviving relatives of the Cambrian explosion? I found the onychophoran pictured to the right while searching under rocks for dwarf geckos in the Sierra de Bahoruco in the Dominican Republic. The Burgess Shale's onychophoran representative (a.k.a. Hallucigenia) may not be as bizarre as Conway Morris or Gould once thought, but this group has no shortage of weird and wonderful habits. One of these can be seen in the form of the sticky strands projecting from this animal's mouth, which are used to subdue prey and repel predators (or the prodding finger of a photographer's assitant). Onycophorans are also known from Dominican amber (1, 2).