How can so many farm state politicians fail to understand the phrase “seed corn”?

Paul Krugman has a lovely phrase to describe Republican policies: Eat the future. They are under pressure to cut spending, any spending, but they refuse to touch anything that might cause immediate pain to the electorate…so instead, anything in the budget that affects future voters is going to get the axe.

Once you understand the imperatives Republicans face, however, it all makes sense. By slashing future-oriented programs, they can deliver the instant spending cuts Tea Partiers demand, without imposing too much immediate pain on voters. And as for the future costs — a population damaged by childhood malnutrition, an increased chance of terrorist attacks, a revenue system undermined by widespread tax evasion — well, tomorrow is another day.

He could have mentioned a few other areas that can be cut, like education, and especially science. Republican voters don’t understand science, they don’t support science, so if there’s anything in the budget that makes Republican politicians salivate in a hungry, predatory way, it’s science. So you won’t be surprised at the prospects for the NIH.

Dear Colleague,

For months the new House leadership has been promising to cut billions in federal funding in fiscal year (FY) 2011. Later this week the House will try to make the rhetoric a reality by voting on HR 1, a “continuing resolution” (CR) that would cut NIH funding by $1.6 billion (5.2%) BELOW the current level – reducing the budget for medical research to $29.4 billion!

We must rally everyone – researchers, trainees, lab personnel – in the scientific community to protest these draconian cuts. Please go to [this link] for instructions on how to call your Representative’s Washington, DC office today! Urge him/her to oppose the cuts to NIH and vote against HR 1. Once you’ve made the call, let us know how it went by sending a short email to the address provided in the call instructions and forward the alert link to your colleagues. We must explain to our Representatives how cuts to NIH will have a devastating impact on their constituents!

Sincerely,

William T. Talman, MD
FASEB President

The cannibals are out there, and they don’t look like you might expect: they wear nice suits and dresses, and they go to church every week, and they are fervent in their patriotism. But they’re planning to eat the future, anyway.

Guinea pigs, please line up here

I have received a request for volunteers to assist as subjects in a research project. I was disappointed; there are no exotic drugs, no catheters, no insane experimental surgeries that will turn you into a super-being with surprising powers beyond all mortal ken, but the fellow did manage to spell my name correctly, so it must be on the up-and-up. Contact Ben Myers (hey! That’s how he got the spelling correct — he cheated!) if you’re interested.

Dr. Myers,

I am an assistant professor of communication studies at USC Upstate. I am in the process of starting a research project and I was wondering if I could ask you for a favor. My research project is centered around atheist/agnostic coming out experiences. For my data, I am planning on collecting stories from those who have “come out” to religious family and friends. I am an ally (and a big fan of your blog). I am interested in this project because of my own very difficult “coming out” experience with my family.
I am planning on doing a rhetorical analysis of common themes across coming out stories. I have included my research plan if you would like more details. Also, I have already received IRB approval for the study.
I will conduct and record interviews over skype. The interviews are open-ended, so I have a few basic questions but I am primarily interested in just letting people tell their stories.
To start the project, I need to find atheists/agnostics who would be willing to share their “coming out” stories. This is where I would like to ask you a favor. I am looking not just for atheist/agnostics, but for atheists/agnostics who have specific “coming out” stories. I am sure there are lots of readers of Pharyngula who would fit the criteria. Would you be willing to dedicate a post to helping me find participants? Perhaps you could post my email and a short blurb about what the research project is about. Participants could then contact me directly.
Also, no need to worry about the project. Any work that results from these interviews will be presented with the ethos of helping readers understand the “coming out” process and how difficult it is. I am an ally, and a proud “out” atheist myself.
Thank you very much for your consideration. And please do not hesitate to ask for additional information if you feel it necessary. And keep on fighting the good fight.

Sincerely,

Ben

—
W. Benjamin Myers, Ph.D.
Assistant Professor of Speech
Department of Fine Arts and Communication Studies
USC Upstate
864.503.5870

Here’s the short research plan.

I have annoyed Jesse Bering

That’s what I do, after all. I strongly criticized his uncritical analysis of a set of rape-related evolutionary psychology studies, and now he responds with a rebuttal. It’s not a very good rebuttal, but I highly recommend his second paragraph in which he lists a good collection of links to several people who also ripped into his article. That part is excellent!

But then let’s get into the part where he argues with me.

P.Z. Myers is not, of course, the undisputed public ambassador of his discipline (although I’ve no doubt he sees himself as such), and by no means does the following apply to all biologists, or even all those who are critical of evolutionary psychology. But Myers’ affect-laden views regarding evolutionary psychology do represent those of at least a significant and vocal minority.

Not an auspicious start to accuse me of regarding myself as “the undisputed public ambassador of” biology, which certainly isn’t the case. This is a blog written by a professor in a small town in rural Minnesota. I’m kind of aware of exactly what it is, and lack the airs Bering wants to assign to me. But then, this isn’t surprising, since most of his following arguments rely on telling me what I intended, and he also gets that wrong. Except this little bit, where he does get the overall objections right.

Critics are particularly irritated by the fact that evolutionary psychologists do not test for genetic inheritance of the very traits they argue are adaptive but instead rely on behavioral or self-report measures to evaluate their theories. They also believe that evolutionary psychologists take too many story-telling liberties in reconstructing the ancestral past, since we can never know for certain what life was like hundreds of thousands of years ago, when such traits would have, theoretically, been favored by natural selection. (This is a point also stressed by Rennie in his critique of my Slate essay.) According to Myers, the whole messy endeavor, therefore, “is a teetering pyramid of stacked ‘couldas’ and guesses that it woulda had an influence on evolution.”

This is actually a reasonable summary of my general disagreements with evolutionary psychology. They are quite fond of inventing evolutionary stories about phenomena that don’t even have an iota of evidence for being genetic, and can come up with truly awesome causal accounts for even the most trivial observations.

He picks out one of my objections to argue why the evolutionary psychology crowd can’t do one of the experiments I didn’t suggest doing, which is a little odd, but OK.

In his post, Myers uses my discussion of the evolution of the human penis as a prime example of the sloppy work being done in the study of evolution and human behavior. He pillories psychologist Gordon Gallup’s famous “dildo study,” which suggests that the distinctive mushroom-capped shape of the penis might serve to scoop a competitor’s semen out of the vagina. (I described this work at long, intimate length in two prior articles in Scientific American.) Myers calls this penis study “tripe” because Gallup and his colleagues failed to show how variations in penis shape within a population–and variations in how the penis is used for coital thrusting–directly affect fertilization rates. Instead, the researchers relied on dildos of different designs, surveys of college students’ detailing their sexual behaviors, and a batch of artificial semen.

Now, I can only assume that Myers has not had to face a university human-research ethics committee in the past several decades. If he had, he would realize that his suggested empirical approach would be unilaterally rejected by these conservative bureaucratic gatekeepers. Does Myers really believe that these seasoned investigators wouldn’t rather have done the full experiment he describes–if only they lived in a less prudish and libellous university world? The fact of the matter is that research psychologists studying human sexuality are hamstrung by necessary ethical constraints when designing their studies. Perhaps Myers would be happy enough to allow investigators into his bedroom to examine the precise depth and vigor to which he plunges into his wife’s vaginal canal after they’ve been separated for a week, but most couples would be a tad more reticent. Gallup’s dildo study, and his related work on penis evolution, offered an ingenious–ingenious–way to get around some very real practical and ethical limitations. Is it perfect? No. Again, the perfect study, conceptually speaking, is often the least ethical one, at least as deemed by research ethics committees. But was it driven by clear, testable, evolutionary hypotheses? Yes. And it offered useful information that was otherwise unknown.

Telling me that they can’t do an experiment that I didn’t suggest doing doesn’t really undermine anything I said. I’m perfectly aware of the ethical limitations of human research, which is one reason why I work on animal models. The problem is that what I actually offered as shortcomings of the work wasn’t their failure to wire up my genitals, but this:

They don’t have any evidence that this behavior actually affects the fertilization rate of one partner’s sperm over another, they don’t have any indication of morphological differences in human populations that make some individuals better semen-scoopers, they don’t have any evidence that this behavior has had a differential effect in human history.

Those are the criteria I would expect to see met in order to discuss this issue as an evolutionary problem; what Bering’s sources were studying were mechanical and physiological aspects of some plumbing (which can be interesting!), and then tacking on unwarranted conclusions about evolutionary history. In fact, I don’t see how Bering’s strange and unexecutable experiment of logging the details of my personal sexual behavior would even touch my evolutionary objections.

He also skips over another relevant point I emphasized. I read the research papers he cited. These were studies that had him “riveted, and convinced”, but when I looked at, for instance, the study that found an increase in women’s handgrip strength during ovulation, the paper itself mentioned that there were many other studies that showed no variation in strength over the menstrual cycle. Which is it? Do you just pick the result that favors your interpretation?

Jerry Coyne has a summary of reactions, too, and mentions several instances where the papers aren’t as clear in their support of the evo-psych hypotheses as is claimed. These are very noisy data that sometimes support and sometimes contradict their claims, and it seems that whatever result they pluck out of the mess, it’s always in support of some purported evolutionarily significant effect on behavior or physiology.

As I said in my previous article, I think the general claim of evolutionary psychology, that our current behavior has been shaped by our biological history, is true. I think much of the research in the field is damaging to their thesis, though, not because it demonstrates the opposite, but because it flits over tiny details, like monthly variations in how a woman moves her hips or how she feels about men, and pretends that they’re all examples of the power of natural selection in sculpting a genome that encodes every pelvic wobble and every nerve impulse. It’s become a kind of modern ornithomancy, where each dip and swirl and change in direction of a flight of birds is interpreted as directly connected to the fate of nations. I remain unconvinced.

What tool would you put in your cognitive toolkit?

The Edge annual question and its answers are out. This year, John Brockman asked, “What scientific concept would improve everybody’s cognitive toolkit?” He got 158 people to send in answers.

I was one of them. If you like my answer, you might also like Sean Carroll’s and Carl Zimmer’s — we seem to have made similar points. Carl has a thread on the topic, and so does Sean: I think I like his original title of dysteleological physicalism better, never mind Carl’s post deploring jargon.

Precious bodily fluids

Last night, I finished reading Paul Offit’s Deadly Choices(amzn/b&n/abe/pwll), his new book about the history of anti-vaccination movements. It’s very good and very thorough and very convincing, and I found it informative because it also takes a broad view, looking everything from the campaigns against Jenner to the crazy talk of Jenny McCarthy. I had never really seen where these opponents of a simple life-saving procedure were coming from, but seeing a few centuries worth of their rhetoric lined up and put on display was helpful, and I finally realized what was wrong with the anti-vaxers.

They’ve all got Jack D. Ripper Syndrome. What drives them nuts is the idea that someone will pollute their (and worse, their children’s) precious bodily fluids with filth and contaminants and base animal substances. It’s a concern about purity and a fear of foreign substances that is amplified beyond all reason; they take a reasonable core concern about cleanliness and avoiding toxins, blow it up into a hysterical terror about a medical procedure that intentionally introduces minute quantities of a foreign substance, and then build pseudoscientific rationalizations for their fear. It’s all gotten a bit ridiculous.

For instance, all the howling about formaldehyde in some vaccines; it’s a trivial amount, a tiny fraction of the quantity your very own metabolism produces in the normal course of a day. If you’re going to get upset about trace formaldehyde in a shot you’ll get once in your life, you ought to be even more upset with your liver, which is trickling more aldehydes than that into your bloodstream every day. Here’s how Offit handles that, in his discussion of the avuncular Dr Bob Sears and his pandering to the anti-vax lobby:

Unfortunately, Sears fails to educate his reader about the importance of quantity—that is, that it’s the dose that makes the poison—and that spacing out vaccines to avoid exposure to quantities of chemicals so small that they have no chance of causing harm will accomplish nothing. For example, Sears claims that formaldehyde is a “carcinogen” (cancer-causing agent) but omits the fact that formaldehyde is a natural product: an essential intermediate in the synthesis of amino acids (the building blocks of proteins) and of thymidines and purines (the building blocs of DNA). Everyone has about two and one-half micrograms of formaldehyde per milliliter of blood. Therefore, young infants have about ten times more formaldehyde circulating in their bodies than is contained in any vaccine. Further, the quanitity of formaldehyde contained in vaccines is at most one six-hundredth of that found to be harmful to animals. It would have been valuable if Sears had informed his readers of these facts rather than scaring them with the notion that formaldehyde in vaccines could cause cancer.

We’re living in a world swarming with all kinds of gunk and goop and dirt and bugs, and some of it is bad for you…but it’s only bad if you get a dose that exceeds your body’s capacity to manage it. The stuff in a vaccine is at such a low concentration and purified to an amazing degree to minimize the quantity of nasties that it contains to a point below the amount that can do anyone harm.

If you’re going to dread a few proteins in a shot, though, I have a tale to make you quiver in disgust. I just had two carrots for lunch, and I didn’t peel them, I just gave them a quick wash in the tap. The quantity of uncharacterized filth and strange chemicals and weird biologically active agents, not to mention the scattered nematodes and bacteria and viruses colonizing the surface of that vegetable, was immense. If I get some random disease in the next day or two, should I blame the carrot farmers of America? Who knows what mysterious pathogens I took into my system via those horrible plants. Farmers raise them in dirt!

(By the way, Orac has a review of Oracian length on this same book. Check it out for the details.)

That’s not an answer

Jonah Lehrer has posted a reply to criticisms of his article on the ‘decline effect’ in science. It doesn’t work, and his arguments miss the mark. As I said, what the statistics show is that science is difficult, and sometimes answers are very hard to come by; that does not justify his attempt to couch the problem in language that suggests a systematic failure of science.

John Allen Paulos is saying the same thing. You can trust him, he’s a professional mathematician.

How to afford a big sloppy genome

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My direct experience with prokaryotes is sadly limited — while our entire lives and environment are profoundly shaped by the activity of bacteria, we rarely actually see the little guys. The closest I’ve come was some years ago, when I was doing work on grasshopper embryos, and sterile technique was a pressing concern. The work was done under a hood that we regularly hosed down with 95% alcohol, we’d extract embryos from their eggs, and we’d keep them alive for hours to days in tissue culture medium — a rich soup of nutrients that was also a ripe environment for bacterial growth. I was looking at the development of neurons, so I’d put the embryo under a high-powered lens of a microscope equipped with differential interference contrast optics, and the sheet of grasshopper neurons would look like a giant’s causeway, a field of tightly packed rounded boulders. I was watching processes emerging and growing from the cells, so I needed good crisp optics and a specimen that would thrive healthily for a good long period of time.

It was a bad sign when bacteria would begin to grow in the embryo. They were visible like grains of rice among the ripe watermelons of the cells I was interested in, and when I spotted them I knew my viewing time was limited: they didn’t obscure much directly, but soon enough the medium would be getting cloudy and worse, grasshopper hemocytes (their immune cells) would emerge and do their amoeboid oozing all over the field, engulfing the nasty bacteria but also obscuring my view.

What was striking, though, was the disparity in size. Prokaryotic bacteria are tiny, so small they nestled in the little nooks between the hopper cells; it was like the opening to Star Wars, with the tiny little rebel corvette dwarfed by the massive eukaryotic embryonic cells that loomed vastly in the microscope, like the imperial star destroyer that just kept coming and totally overbearing the smaller targets. And the totality of the embryo itself — that’s no moon. It’s a multicellular organism.

I had to wonder: why have eukaryotes grown so large relative to their prokaryotic cousins, and why haven’t any prokaryotes followed the strategy of multicellularity to build even bigger assemblages? There is a pat answer, of course: it’s because prokaryotes already have the most successful evolutionary strategy of them all and are busily being the best microorganisms they can be. Evolving into a worm would be a step down for them.

That answer doesn’t work, though. Prokaryotes are the most numerous, most diverse, most widely successful organisms on the planet: in all those teeming swarms and multitudinous opportunities, none have exploited this path? I can understand that they’d be rare, but nonexistent? The only big multicellular organisms are all eukaryotic? Why?

Another issue is that it’s not as if eukaryotes carry around fundamentally different processes: every key innovation that allowed multicellularity to occur was first pioneered in prokaryotes. Cell signaling? Prokaryotes have it. Gene regulation? Prokaryotes have that covered. Functional partitioning of specialized regions of the cell? Common in prokaryotes. Introns, exons, endocytosis, cytoskeletons…yep, prokaryotes had it first, eukaryotes have simply elaborated upon them. It’s like finding a remote tribe that has mastered all the individual skills of carpentry — nails and hammers, screws and screwdrivers, saws and lumber — as well as plumbing and electricity, but no one has ever managed to bring all the skills together to build a house.

Nick Lane and William Martin have a hypothesis, and it’s an interesting one that I hadn’t considered before: it’s the horsepower. Eukaryotes have a key innovation that permits the expansion of genome complexity, and it’s the mitochondrion. Without that big powerplant, and most importantly, a dedicated control mechanism, prokaryotes can’t afford to become more complex, so they’ve instead evolved to dominate the small, fast, efficient niche, leaving the eukaryotes to occupy the grandly inefficient, elaborate sloppy niche.

Lane and Martin make their case with numbers. What is the energy budget for cells? Somewhat surprisingly, even during periods of rapid growth, bacteria sink only about 20% of their metabolic activity into DNA replication; the costly process is protein synthesis, which eats up about 75% of the energy budget. It’s not so much having a lot of genes in the genome that is expensive, it’s translating those genes into useful protein products that costs. And if a bacterium with 4400 genes is spending that much making them work, it doesn’t have a lot of latitude to expand the number of genes — double them and the cell goes bankrupt. Yet eukaryotic cells can have ten times that number of genes.

Another way to look at it is to calculate the metabolic output of the typical cell. A culture of bacteria may have a mean metabolic rate of 0.2 watts/gram; each cell is tiny, with a mass of 2.6 x 10-12g, which means each cell is producing about 0.5 picowatts. A eukaryotic protist has about the same power output per unit weight, 0.06 watts/gram, but each cell is so much larger, about 40,000 x 10-12g, that a single cell has about 2300 picowatts available to it. So, more energy!

Now the question is how that relates to genome size. If the prokaryote has a genome that’s about 6 megabases long, that means it has about 0.08 picowatts/megabase to spare. If the eukaryote genome is 3,000 megabytes long, that translates into about 0.8 picowatts of power per megabase (that’s a tenfold increase, but keep in mind that there is wide variation in size in both prokaryotes and eukaryotes, so the ranges overlap and we can’t actually consider this a significant difference — they’re in the same ballpark).

Now you should be thinking…this is just a consequence of scaling. Eukaryotic power production per gram isn’t any better than what prokaryotes do, all they’ve done is made their cells bigger, and there’s nothing to stop prokaryotes from growing large and doing the same thing. In fact, they do: the largest known bacterium, Thiomargarita, can reach a diameter of a half-millimeter. It gets more metabolic power in a similar way to how eukaryotes do it: we eukaryotes carry a population of mitochondria with convoluted membranes and a dedicated strand of DNA, all to produce energy, and the larger the cell, the more mitochondria are present. Thiomargarita doesn’t have mitochondria, but it instead duplicates its own genome many times over, with 6,000-17,000 nucleoids distributed around the cell, each regulating its own patch of energy-producing membrane. It’s functionally equivalent to the eukaryotic mitochondrial array then, right?

Wrong. There’s a catch. Mitochondria have grossly stripped down genomes, carrying just a small cluster of genes essential for ATP production. One hypothesis for why this mitochondrial genome is maintained is that it acts as a local control module, rapidly responding to changes in the local membrane to regulate the structure. In Thiomargarita, in order to get this fine-tuned local control, the whole genome is replicated, dragging along all the baggage, and metabolic expense, of all of those non-metabolic genes.

Because it is amplifying the entire genomic package instead of just an essential metabolic subset, Thiomargarita‘s energy output per gene plummets in comparison. That difference is highlighted in this illustration which compares an ‘average’ prokaryote, Escherichia, to a giant prokaryote, Thiomargarita, to an ‘average’ eukaryotic protist, Euglena.

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(Click for larger image)
The cellular power struggle. a-c, Schematic representations of a medium sized prokaryote (Escherichia), a very large prokaryote (Thiomargarita), and a medium-sized eukaryote (Euglena). Bioenergetic membranes across which chemiosmotic potential is generated and harnessed are drawn in red and indicated with a black arrow; DNA is indicated in blue. In c, the mitochondrion is enlarged in the inset, mitochondrial DNA and nuclear DNA are indicated with open arrows. d-f, Power production of the cells shown in relation to fresh weight (d), per haploid gene (e) and per haploid genome (power per haploid gene times haploid gene number) (f). Note that the presence or absence of a nuclear membrane in eukaryotes, although arguably a consequence of mitochondrial origin70, has no impact on energetics, but that the energy per gene provided by mitochondria underpins the origin of the genomic complexity required to evolve such eukaryote-specific traits.

Notice that the prokaryotes are at no disadvantage in terms of raw power output; eukaryotes have not evolved bigger, better engines. Where they differ greatly is in the amount of power produced per gene or per genome. Eukaryotes are profligate in pouring energy into their genomes, which is how they can afford to be so disgracefully inefficient, with numerous genes with only subtle differences between them, and with large quantities of junk DNA (which is also not so costly anyway; remember, the bulk of the expense is in translating, not replicating, the genome, and junk DNA is mostly untranscribed).

So, what Lane and Martin argue is that the segregation of energy production into functional modules with an independent and minimal genetic control mechanism, mitochondria with mitochondrial DNA, was the essential precursor to the evolution of multicellular complexity — it’s what gave the cell the energy surplus to expand the genome and explore large-scale innovation.

As they explain it…

Our considerations reveal why the exploration of protein sequence space en route to eukaryotic complexity required mitochondria. Without mitochondria, prokaryotes—even giant polyploids—cannot pay the energetic price of complexity; the lack of true intermediates in the prokaryote-to-eukaryote transition has a bioenergetic cause. The conversion from endosymbiont to mitochondrion provided a freely expandable surface area of internal bioenergetic membranes, serviced by thousands of tiny specialized genomes that permitted their host to evolve, explore and express massive numbers of new proteins in combinations and at levels energetically unattainable for its prokaryotic contemporaries. If evolution works like a tinkerer, evolution with mitochondria works like a corps of engineers.

That last word is unfortunate, because they really aren’t saying that mitochondria engineer evolutionary change at all. What they are is permissive: they generate the extra energy that allows the nuclear genome the luxury of exploring a wider space of complexity and possible solutions to novel problems. Prokaryotes are all about efficiency and refinement, while eukaryotes are all about flamboyant experimentation by chance, not design.

Lane N, Martin W. (2010) The energetics of genome complexity. Nature 467(7318):929-34.

The molecular foundation of the phylotypic stage

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When last we left this subject, I had pointed out that the phenomenon of embryonic similarity within a phylum was real, and that the creationists were in a state of dishonest denial, arguing with archaic interpretations while trying to pretend the observations were false. I also explained that constraints on morphology during development were complex, and that it was going to take something like a thorough comparative analysis of large sets of gene expression data in order to drill down into the mechanisms behind the phylotypic stage.

Guess what? The comparative analysis of large sets of gene expression data is happening. And the creationists are wrong, again.

Again, briefly, here’s the phenomenon we’re trying to explain. On the left in the diagram below is the ‘developmental hourglass’: if you compare eggs from various species, and adults from various species, you find a diversity of forms. However, at one period in early development called the phylytypic stage (or pharyngula stage specifically in vertebrates), there is a period of greater similarity. Something is conserved in animals, and it’s not clear what; it’s not a single gene or anything as concrete as a sequence, but is instead a pattern of interactions between developmentally significant genes.

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The diagram on the right is an explanation for the observations on the left. What’s going on in development is an increase in complexity over time, shown by the gray line, but the level of global interactions does not increase so simply. What this means is that in development, modular structures are set up that can develop autonomously using only local information; think of an arm, for instance, that is initiated as a limb bud and then gradually differentiates into the bones and muscle and connective tissue of the limb without further central guidance. The developing arm does not need to consult with the toes or get information from the brain in order to grow properly. However, at some point, the limb bud has to be localized somewhere specific in relation to the toes and brain; it does require some sort of global positioning system to place it in the proper position on the embryo. What we want to know is what is the GPS signal for an embryo: what it looks like is that that set of signals is generated at the phylotypic stage, and that’s why this particular stage is relatively well-conserved.

One important fact about the diagram above: the graph on the right is entirely speculative and is only presented to illustrate the concept. It’s a bit fake, too—the real data would have to involve multiple genes and won’t be reducible to a single axis over time in quite this same way.

Two recent papers in Nature have examined the real molecular information behind the phylotypic stage, and they’ve confirmed the molecular basis of the conservation. Of course, by “recent”, I mean a few weeks ago…and there have already been several excellent reviews of the work. Matthew Cobb has a nice, clean summary of both, if you just want to get straight to the answer. Steve Matheson has a three part series thoroughly explaining the research, so if you want all the details, go there.

In the first paper by Kalinka and others, the authors focused on 6 species of Drosophila that were separated by as much as 40 million years of evolution, and examined quantitative gene expression data for over 3000 genes measured at 2 hour intervals. The end result of all that work is a large pile of numbers for each species and each gene that shows how expression varies over time.

Now the interesting part is that those species were compared, and a measure was made of how much the expression varied: that is, if gene X in Drosophila melanogaster had the same expression profile as the homologous gene X in D. simulans, then divergence was low; if gene X was expressed at different times to different degrees in the two species, then divergence was high. In addition, the degree of conservation of the gene sequences between the species were also estimated.

The prediction was that there ought to be a reduction of divergence during the phylotypic period. That is, the expression of genes in these six species should differ the least in developmental genes that were active during that period. In addition, these same genes should show a greater degree of evolutionary constraint.

Guess what? That’s exactly what they do see.

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Temporal expression divergence is minimized during the phylotypic period. a, Temporal divergence of gene expression at individual time points during embryogenesis. The curve is a second-order polynomial that fits best to the divergence data. Embryo images are three-dimensional renderings of time-lapse embryonic development of D. melanogaster using Selective Plane Illumination Microscopy (SPIM).

That trough in the graph represents a period of reduced gene expression variance between the species, and it corresponds to that phylotypic period. This is an independent confirmation of the morphological evidence: the similarities are real and they are an aspect of a conserved developmental program.

By the way, this pattern only emerges in developmental genes. They also examined genes involved in the immune system and metabolism, for instance, and they show no such correlation. This isn’t just a quirk of some functional constraint on general gene expression at one stage of development, but realy is something special about a developmental and evolutionary constraint.

The second paper by Domazet-Loso and Tautz takes a completely different approach. They examine the array of genes expressed at different times in embryonic development of the zebrafish, and then use a comparative analysis of the sequences of those genes against the sequences of genes from the genomic databases to assign a phylogenetic age to them. They call this phylostratigraphy. Each gene can be dated to the time of its origin, and then we can ask when phylogenetically old genes tend to be expressed during development.

The prediction here is that there would be a core of ancient, conserved genes that are important in establishing the body plan, and that they would be expressed during the phylotypic stage. The divergence at earlier and later stages would be a consequence of more novel genes.

Can you guess what they saw? Yeah, this is getting predictable. The observed pattern fits the prediction.

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Transcriptome age profiles for the zebrafish ontogeny. a, Cumulative transcriptome age index (TAI) for the different developmental stages. The pink shaded area represents the presumptive phylotypic phase in vertebrates. The overall pattern is significant by repeated measures ANOVA (P = 2.4 3 10-15, after Greenhouse-Geisser correction P = 0.024). Grey shaded areas represent ± the standard error of TAI estimated by bootstrap analysis.

So what does this all tell us? That the phylotypic stage can be observed and measured quantitatively using several different techniques; that it represents a conserved pattern of development gene expression; and that the genes involved are phylogenetically old (as we’d expect if they are conserved.)

Domazet-Loso and Tautz propose two alternative explanations for the phenomenon, one of which I don’t find credible.

Adaptations are expected to occur primarily in response to altered ecological conditions. Juvenile and adults interact much more with ecological factors than embryos, which may even be a cause for fast postzygotic isolation. Similarly, the zygote may also react to environmental constraints, for example, via the amount of yolk provided in the egg. In contrast, mid-embryonic stages around the phylotypic phase are normally not in direct contact with the environment and are therefore less likely to be subject to ecological adaptations and evolutionary change. As already suggested by Darwin, this alone could explain the lowered morphological divergence of early ontogenetic stages compared to adults, which would obviate the need to invoke particular constraints. Alternatively, the constraint hypothesis would suggest that it is difficult for newly evolved genes to become recruited to strongly connected regulatory networks.

They propose two alternatives, that the phylotypic stage is privileged and therefore isn’t being shaped by selection, or that it is constrained by the presence of a complicated gene network, and therefore is limited in the amount of change that can be tolerated. The first explanation doesn’t make sense to me: if a system is freed from selection, then it ought to diverge more rapidly, not less. I’m also baffled by the suggestion that the mid-stage embryos are not in direct contact with the environment. Of course they are…it’s just possible that that mid-development environment is more stable and more conserved itself.

What we need to know more about is the specifics of the full regulatory network. A map of the full circuitry, rather than just aggregate measures of divergence, would be nice. I’m looking forward to it!

The creationists aren’t, though.

Domazet-Loso, T., & Tautz, D. (2010). A phylogenetically based transcriptome age index mirrors ontogenetic divergence patterns. Nature 468 (7325): 815-818. DOI: 10.1038/nature09632

Kalinka, A., Varga, K., Gerrard, D., Preibisch, S., Corcoran, D., Jarrells, J., Ohler, U., Bergman, C., Tomancak, P. (2010). Gene expression divergence recapitulates the developmental hourglass model. Nature 468 (7325): 811-814 DOI: 10.1038/nature09634

It seems a waste of vodka

Somebody is angling for an Ig-Nobel, I think. Apparently, it’s a Danish myth that you can absorb alcohol through your feet, so soaking your feet in a tub of spirits is a way to get drunk (they also mention that soaking your feet in beet juice will make your urine red, but they didn’t test that one, unfortunately). So the hypothesis that one can get drunk through your feet was thoroughly tested.

The participants abstained from consuming alcohol 24 hours before the experiment. The evening before the experiment they rubbed their feet with a loofah to remove skin debris. On the day of the experiment, a baseline blood sample was taken through a venous line. The participants then submerged their feet in a washing-up bowl containing the contents of three 700 mL bottles of vodka (Karloff vodka; M R Štefánika, Cífer, Slovakia, 37.5% by volume). Before each blood sample was taken the venous catheter and cannula were flushed with saline by a trained study nurse. Plasma ethanol concentrations were determined every 30 minutes for three hours. Blood samples were taken to the laboratory for immediate analysis by the study nurse. Plasma ethanol concentrations, measured as soon as possible in case of rapid and potentially fatal increases, were determined using a photometric method, with a detection limit of 2.2 mmol/L (10 mg/100 mL, corresponding to 0.010% weight/volume). Participants simultaneously recorded intoxication related symptoms (self confidence, urge to speak, and number of spontaneous hugs) on an arbitrary scale from 0 to 10.

The results: it didn’t work. Blood alcohol levels didn’t even rise to testable levels, and no one felt an urge to start hugging.

I’m sure you’re all disappointed now. If you’re disappointed because we don’t know what happened to the 2100 mL of vodka after the experiment, you should be worried about your possible alcoholism.

The authors left several questions open.

Many questions are still to be answered in the research specialty of alcohol transport across non-gastrointestinal barriers. This study has shown that feet are impenetrable to the alcohol component of Karloff vodka. Other stronger beverages, beetroot juice, or combinations of juices and alcoholic beverages may, however, cross the epithelial barrier of the skin. Moreover, new pastimes, such as “eyeball drinking,” have emerged. The significance of this activity is unknown. Rumour has it that it makes you drunk fast . . . and may damage your eyes.

Wait. Eyeball…drinking? What’s up with those Danes?