What I taught today: heavy on the epistasis

Today we talked about gap genes and a little bit about pair rule genes in flies, and to introduce the topic I summarized genetic epistasis. Epistasis is a fancy word for the interactions between genes, and we’ve already discussed it on the simplest level. You can imagine that a gene A, when expressed, activates the expression of gene B. The arrow in this diagram? That’s epistasis.

epi1

So far, so simple. This could describe how bicoid activates zygotic hunchback for instance. But of course not all epistatic interactions are linear and one dimensional; often one transcription factor will turn on or repress multiple genes — so A might switch on genes B, C, and D.

epi2

But wait! Now there is the potential for all kinds of combinatorial interactions: maybe C has positive feedback back on A, and B activates D and C, and D activates B, and C represses B. There’s a whole mathematically bewildering world of possibility here.

epi3

And it gets worse and worse. B, C, and D could have downstream effects on other genes, like E, F, G, and H, and each of those interact with each other and can have feedback effects as well. It’s not at all uncommon to be taking apart the sequence of events of a developmental pathway and discover a whole tangled snarl of epistatic interactions that lead to complicated patterns of gene expression.

epi4

And that’s molecular geneticists and developmental biologists do: they try to tease apart the snarl, asking how each gene interacts with all the other genes in the system, working out the kind of genetic circuitry shown in those diagrams. Often the approach is take it one gene at a time: knock out F, for instance, and ask what happens to the expression patterns of A, B, C, D, E, G, and H. Or upregulate D, and ask what all those other genes do. If you like logic puzzles, you’ll love epistatic studies, because that’s what they are: grand complicated logic puzzles with multiple cascading effects and usually only partial knowledge about what each component does. You’ll either have great fun with it all, or cultivate great headaches.

So most of the class hour was spent going through examples of these puzzles. The gap genes, for instance, are expressed in broad stripes in the embryo, and we can try to decipher the rules that establish the boundaries by taking out components. If hunchback is deleted, what do the giant, krüppel, and knirps stripes look like? Take out krüppel, what happens to knirps? So I led them through this series of experiments, asking them to come up with general rules regulating the expression of each stripe, and then using those rules to predict what would happen if we did a different experiment. I think they mostly got it.

But of course the discussion today was mostly about the gap genes, which are the second tier of genetic interactions (analogous to my third figure above). Next I introduced the pair rule genes, the third tier, rather like my fourth diagram. These are genes that are expressed in alternating stripes corresponding to parasegments in the fly…so we’ve gone from a few broad stripes to many narrow stripes. Each of those stripes, too, is independently regulated, with distinct control regions for each.

The real nightmare begins in the next class, when we start taking apart the many ways all of the pair rule genes interact with each other, and how their position is established partly by regulation by the gap genes and partly by mutual sorting out with combinations of activating and repressing interactions. It’s going to be loads of fun!

Today’s slides.

A little blogging exercise for my students

In my development class, students have been blogging away for the last few weeks, and I asked them to send me links to ones they wouldn’t mind seeing advertised. I’ve told them that an important part of effectively blogging is to link and comment, so they’re supposed to write something this week that adds to one of these posts and links to it on their own blog, and they’re also supposed to leave a comment on their fellow students’ work.

I warned them too that I’d highlight these publicly and urge my readers to look and say a few things: so go ahead and comment, criticize, praise, whatever — I told them that the good will come with the bad.

I suspect I’ll have to explain to them how to kill spam and remove irrelevant or outrageous comments in the next class…

I’ve been being mainly non-verbal today

Mainly because I’ve been writing like a fiend for the last two weeks when I haven’t been driving across the state. So I took a couple days away from the computer, mostly.

Went on a little seven-mile round trip hike in the National Park next door. No great feat compared to what I used to do routinely, especially since the total elevation gain was less than 500 feet. But it’s the first hike of that length I’ve done in some months, so it did me more or less in. Especially the part about the mile and a half furthest from the trailhead being on deep sand. Which meant three miles hiked on deep sand, as I had to come back. Ow my aching lower extremities.

Along the Boy Scout Trail in Joshua Tree National Park

The trail led to Willow Hole, a seasonal wetland with the aforementioned trees in the middle of the bouldery part of the park called the Wonderland of Rocks:

Untitled

Just upstream from Willow Hole.

Got there, sat, drank water, heard my favorite desert birdsong, from the canyon wren (Catherpes mexicanus):


[Source]

All in all, a good day. Ow.

Taking the wonder back

Oh, how I hate this stupid question:

Many popular scientists are atheist, so why are they so happy to use the misty-eyed language of religion?

Check your assumptions, journalist. Why do you associate feelings of wonder and awe with fucking religion? Look at the stuff she quotes from prominent scientists: it has nothing to do with religion, except that religion has spent millennia appropriating these ideas.

It’s ironic that the public engagement with the science crowd is so pro-wonder, because they’re so anti-religion. "All the great religions have a place for awe, for ecstatic transport at the wonder and beauty of creation," writes Richard Dawkins. "And it’s exactly this feeling of spine-shivering, breath-catching awe – almost worship – this flooding of the chest with ecstatic wonder, that modern science can provide."

"I’m an atheist," said maths professor Marcus du Sautoy when he took up the Charles Simonyi chair in the public understanding of science at Oxford. "But for me the important thing is the wonder of science." Advocates for science can’t seem to give up on religion’s selling points: the awe, transcendence, and worship.

Notice what the godbots have managed to do: they have taken a child’s delight in the natural world, stolen it, and said, “Awe belongs to god; you aren’t thrilled with dandelion fluff, stars in the sky, or the leap of an antelope, you’re really feeling ecstasy at gods and the supernatural.”

That’s a lie. The scientists are taking back a stolen joy and placing it where it belongs: in our universe, in our natural world, in us. The journalists should be asking instead how we got so duped that we take it for granted that we’re worshipping an invisible man when we find happiness in a clear warm sky and the scent of grass on the wind and a calm sense of our place on Earth.

That isn’t the language of religion. The language of religion is dominion, tribalism, ignorance, and fear.

We are the WEIRD

Western, Educated, Industrialized, Rich, and Democratic, that is. One of the common complaints about evolutionary psychology is that it claims to be addressing evolved human universals, but when you look at the data sets, they are almost always drawn from the same tiny pool of outliers, Western undergraduate students enrolled in psychology programs, and excessively extrapolated to be representative of Homo sapiens — when we’re actually a very peculiar group.

How peculiar? A paper by Henrich, Heine, and Norenzayan, “The Weirdest People in the World”, tries to measure that…and by nearly every standard they looked at, the wealthy inhabitants of democratic western societies are not exactly normal (that is, they’re far from average in ways both good and bad and value neutral).

Who are the people studied in behavioral science research? A recent analysis of the top journals in six sub‐disciplines of Psychology from 2003‐2007 revealed that 68% of subjects came from the US, and a full 96% of subjects were from Western industrialized countries, specifically North America, Europe, Australia, and Israel (Arnett 2008). The make‐up of these samples appears to largely reflect the country of residence of the authors, as 73% of first authors were at American universities, and 99% were at universities in Western countries. This means that 96% of psychological samples come from countries with only 12% of the world’s population. Put another way, a randomly selected American is 300 times more likely to be a research participant in a study in one of these journals than is a randomly selected person from outside of the West.

It’s even worse: “67% of the American samples (and 80% of the samples from other countries) were composed solely of undergraduates in psychology courses”.

That wouldn’t be so bad if we were examining traits that were truly universal, or if we had a better understanding of exactly what properties were unusual and derived. Fruit flies are also real oddball organisms, but we can still learn a lot from taking them apart…as long as we don’t simply pretend that people and mice and beetles and clams are all just like flies. Lab rats have their place, but understanding the bigger picture needs more diversity.

So it is possible that maybe the results aren’t significantly biased by sampling error if there weren’t much variation anyway. Unfortunately for the psychological universalists, that doesn’t seem to be the case. The paper describes many differences between cultures, some of which one might be willing to argue are fairly superficial: some societies have homosexual activities as an important step in the rituals of becoming a man, for instance, and while many of us might find that uncomfortable, we can see a range of sexual preferences even within the WEIRD group. But others violate properties I’ve always taken for granted.

mueller-lyer

For instance, in neuroscience and psychology you’ll see this optical illusion all the time, the Mueller-Lyer illusion. The two lines are exactly the same length, but we perceive them as longer or shorter depending on the direction of the arrows.

Wait, “we”? Yeah, I do, most of you readers probably do too, and every time I’ve seen this illusion in the text books it’s presented as a fait accompli — but of course you will see this dramatic illustration of how the brain processes visual stimuli!

Only, they don’t. The magnitude of the effect is culture-dependent. In a series of tests in which the lines were adjusted until the viewer saw them as equal in length, different groups saw different things. The WEIRD group needed one line extended a great deal before they saw them as equal; the African San scarcely saw the illusion at all.

ml_cultures
Mueller‐Lyer Results for Segall et. al.’s cross‐cultural project. PSE is the percentage that segment ‘a’ must be longer than ‘b’ before individuals perceive them as equal.

The paper goes through multiple examples of this kind of variable phenomena: economic decision making (not everyone thinks like a trader), biological reasoning (Western people are marked by a deep ignorance of other organisms), spatial cognition (how do you see yourself and others relative to landmarks?), and the individual’s relationship to society. They also identify properties that do seem to be common across populations…and that’s the nub of the argument here.

No one is denying that there are almost certainly deep commonalities between all members of our species. But there are also phenomena that are much more fluid, and sometimes those phenomena are so deeply ingrained in contemporary culture that we assume that they must be human universals — we assume our personal differences and biases must be shared by all right-thinking, decent human beings. But you can’t know that until you look, and your personal prejudices do not count as data.

It takes hard work to identify the real common threads of our humanity, and it can be rewarding to see which bits of our identity are actually superficial, not an essential part of our generally human self. The authors advocate more care in interpretation and wider empirical research.

Many radical versions of cultural relativity deny any shared commonalities in human psychologies across populations. To the contrary, we expect humans from all societies to share, and probably share substantially, basic aspects of cognition, motivation, and behavior. As researchers who see much value in applying evolutionary thinking to psychology and behavior, we have little doubt that if a full accounting were taken across all domains among peoples past and present, that the number of similarities would indeed be large, as much ethnographic work suggests (e.g., Brown 1991)—ultimately, of course, this is an empirical question. Thus, our thesis is not that humans share few basic psychological properties or processes; rather we question our current ability to distinguish these reliably developing aspects of human psychology from more developmentally, culturally, or environmentally contingent aspects of our psychology given the disproportionate reliance on WEIRD subjects. Our aim here, then, is to inspire efforts to place knowledge of such universal features of psychology on a firmer footing by empirically addressing, rather than dismissing or ignoring, questions of population variability.

Perspective is needed. The ridiculous bias in most psychology studies might be unavoidable — not every undergraduate psychology can afford to fly to deepest Uganda or the Chinese hinterlands to broaden the cultural background of their research — but we could at least have greater caution in claiming breadth. I thought this suggestion was amusing:

Arnett (2008) notes that psychologists would surely bristle if journals were renamed to more accurately reflect the nature of their samples (e.g., Journal of Personality and Social Psychology of American Undergraduate Psychology Students). They would bristle, presumably, because they believe that their findings would broadly generalize. Of course, there are important exceptions to this general tendency as some researchers have assembled a broad database to provide evidence for universality (e.g., Buss 1989, Daly & Wilson 1988, Tracy & Matsumoto 2008).

I don’t think the specificity of that journal title would diminish its interest, and it would be a heck of a lot more accurate. We already have specialty science journals for Drosophila, zebrafish, nematodes, etc., so why not give the American Undergraduate Psychology Students the recognition they deserve as a standard model organism?

(via The Pacific Standard)

Please don’t use this argument

I got briefly drawn into a twitter argument with a fellow atheist who proudly flashed this image:

badarg
The next time you get bullied by religious people on facebook, remind them that they are using hardware and software invented and built by atheists, including facebook!

That is embarassingly bad. And when I pointed out a few of the flaws in that claim (briefly, ala twitter), he just repeated the claim and then accused me of trolling.

Look, it’s a terrible argument. It annoys me in multiple ways.

  • Have you ever heard Christians claim that all of science is built on a Judeo-Christian foundation? I sure have (WARNING: Creationist video on autoplay at link!). I’ve been told many times that Newton didn’t believe in evolution. It sounds stupid when they say it, it sounds stupid when atheists say it.

  • What, do you really think there are no religious scientists and engineers? Tim Berners-Lee is a Unitarian Universalist. Guglielmo Marconi was both a Catholic and an Anglican. James Clerk Maxwell was a Baptist. I mean, seriously, you’re going to claim our modern technological world is the product of atheists, and you’re going to ignore Maxwell? Jebus. Pretty strong selection bias you’ve got there.

  • I die a little bit inside when you tell me that your paragon of techno-atheist excellence is Mark Zuckerberg and Facebook. Who thinks that Facebook was something that couldn’t possibly have been invented by a devout Christian?

  • All anyone needs to do is cite one Christian who worked on the development of the internet, and your argument dies. Is it wise to stake your claim to something all it takes is one counterexample to shoot down?

  • I notice all the exemplars in the picture are white men. Keep using this logic; let’s start bragging to everyone on the internet that they are using hardware and software invented and built by white people. It’s the same argument. Do you see the flaws yet?

  • We are living in an interesting little bubble of time in which our best educated, most economically stable people are drifting into more secular ways of thinking. Odds are that if you’re sufficiently secure economically that you can go to Harvard in a tech field, even so secure that you can drop out of Harvard, you’re also likely to be secular or liberally religious, and you’re also more likely to be white. Do not confuse cause and effect. You are succeeding because being godless and pale-skinned gives you an edge — you’re looking at people who started out on third base. It’s not because being godless gives you special science powers.

You are not going to find many people who are more adamant than I am that religion and science are incompatible — they are fundamentally different ways of determining the validity of truth claims, and one works while the other perpetuates garbage — but I am not going to confuse that with an incompatibility between religious people and science. Scientists who are religious are quite capable of setting aside supernatural beliefs to work well and succeed in the lab. Being an atheist doesn’t turn you into a scientist or engineer. Avoiding church doesn’t make you a better scientist or engineer — practicing science, no matter how silly the hobbies you practice in your spare time, does that.

Screw it, gimme a steak

As I’ve been shedding the meat from my diet, I don’t need discouragement like this: a fellow ate a vegetarian burrito and picked up a tapeworm from it, which infected his brain. Is there to be no reward for virtue?

Of course, when you think about the mode of transmission, it probably got into the burrito by way of the poor hygiene of the cook, who’d either been handling raw meat or feces…

Wait, take it away, suddenly I don’t want the steak, either.

What I taught today: the great cis vs trans debate

My students get a full exposure to the Sean Carroll perspective in his book, Endless Forms Most Beautiful, and I’m generally pro-evo devo throughout my course. I do try to make them aware of the bigger picture, though, so today we had an in-class discussion/’debate’ (nothing so formal as a debate, and it was more a tool to make them think about the arguments than to actually resolve a question). Fortunately, there’s one really easy exercise we can do in developmental biology, because some big names in the field have already clearly laid out their positions in a couple of relatively succinct papers, so I had a shortcut to bring the students up to speed on the issues. I split the class on Monday, having half read a paper by Hoekstra and Coyne on “The locus of evolution: evo devo and the genetics of adaptation” (pdf), which argues for the importance of trans-acting mutations in evolution, and another by Wray on “The evolutionary significance of cis-regulatory mutations” (pdf), which argues for the importance of developmental changes through changes in cis regulatory regions.

I drew this little cartoon on the board to illustrate the situation: that changes in the coding regions of genes produce mutations that can have broader effects throughout the cell (trans: they can affect other genes not on the same chromosome), while changes in regulatory DNA will have discrete effects on just the gene on the same strand of DNA they are (cis).

cistrans

Then I asked them put together an argument as a group advocating for the significance to evolution of their ‘side’, cis or trans, which they then delivered to their opponent, with opportunities for rebuttal and counter-rebuttal.

Ah, pitting the students against one another…always the fun part of teaching.

There was good friendly discussion. Both sides had to dig into their respective papers to find the arguments, and then restate them to make their point, both of which are good exercises. The battle waged to and fro, and then our hour was up and I asked them to vote for who ‘won’, in the subjective sense of making a good argument and persuasively advancing their position. The results:

Which position do you think makes the best case for the significance of their phenomenon in evolution?

Team trans: 1
Team cis: 0
Both positions are important: 8

Minnesota mildness for the win!

I did think one student comment was perceptive and exposed the whole argument for a sham. If they were to go off to graduate school in developmental biology, they wouldn’t be picking Team trans or Team cis: they’d be pursuing a phenotype or a pattern of interest, and then analyzing how it worked and came to be, and they’d simply accept the evidence, cis or trans or both, however it turned out. Follow the data, always.

Now that’s a healthy attitude.

Halos in the sky

I just got back from this evening’s Cafe Scientifique — where were you guys? — and I got to see lots of pretty pictures of halos and sundogs and light pillars. One of the nice things about living in Morris is that we actually get a lot of that weird atmospheric phenomena here, because we have lots of the raw material for them here: ice crystals. Vast drifting clouds of hexagonal crystals, flat and columnar, of various proportions, floating in the sky at various orientations to both refract and reflect light into our eyes.

I won’t go into all the details, since you weren’t there. And since most of you live in a less blessed place than the cold crisp upper midwest in the wintertime, you won’t get to see them, because your wicked heat melts all those sharp edged crystals into sludgy droopy droplets. Sorry. But I wanted to pass along one tip.

There’s some free software called Halosim that lets you do simulations of ice crystal distributions in the atmosphere. You specify their sizes and proportions and shapes, and then it traces the paths of light rays and produces an idealized image of what you should be able to see.

HaloSim

It’s very cool. You can tinker and see that to make dramatic sundogs, for instance, you need lots of flat hexagonal platelets floating in a mostly horizontal orientation, and presto, you’ll get a pair of virtual suns 22° to either side of the real one.

Well, maybe you can do that. It’s PC only, so I can’t run any of the simulations on my home computers myself. I’ll have to settle for looking at the real thing, darn it.