When will we wake up?

We had organic solvents dumped into West Virginia rivers thanks to lack of regulatory concern. We’ve got Republicans rah-rah-rahing for fracking, which risks our aquifers…and of course, they want to run the leaky ol’ XL pipeline across our midwestern farmland. And now 400,000 people in Ohio are without drinking water, and are draining the markets in Michigan of bottled water. What’s causing this problem?

The annual algae blooms have been concentrated around the western end of Lake Erie. The algae growth is fed by phosphorous mainly from farm fertilizer runoff and sewage treatment plants, leaving behind toxins that can kill animals and sicken humans.

Somehow, we seem oblivious to the fact that we can’t poison our environment and also have a good quality of life. You can’t just say, “I’ve got good water now,” and then neglect the infrastructure that maintains that water, or worse yet, charge off and let people profit by wrecking it.

2 + 2 = 17, for certain values of 2

A while back, I responded to Behe/Luskin’s claim that his model proving the impossibility of evolution of chloroquinone resistance was vindicated. I pointed out (as did Ken Miller) that showing that a particular trait required multiple point mutations did not affect the probability in the naive way that Behe and Luskin calculated — in particular, it did not require that the mutations be simultaneous. We’re familiar with a great many known mutations that involve multiple sequential hits to have their effect. I mentioned the work on steroid receptor evolution, and how cancer is an amazing example of the power of the accumulation of sequential variants.

Behe fired back, issuing a challenge to ‘show my numbers’. If he could have said anything to confirm that he was obliviously ignoring my point, that was it, and so I blew him a raspberry and ignored his challenge. I wasn’t arguing with his numbers, and we could even use his very own set of numbers — my point was in the operation he was doing with those numbers. His assumption is that you must have two mutations occur simultaneously, in the same individual, so that you simplistically multiply the probabilities together to get an improbably low frequency. I’m saying that’s invalid: these mutations can happen independently, they can accumulate to some frequency in the population, and then a second mutation can occur.

Now Larry Moran has carried through on the calculations. Using the known data on mutation rates, and throwing away Behe’s bogus demand that everything occur in the very same instant, he shows that the evolution of chloroquinone resistance ought to be rare, but not at all impossible, and with frequencies that are in the ballpark of what is observed.

Furthermore, Moran describes a paper that quantifies the presence of malaria strains in the population that contain pieces of the resistant combinations and that further describe the sequential series of mutational events that led to the most resistant strains.

All of the strains (except D17) are found in naturally occurring Plasmodium populations and the probable pathways to each of the major chloroquine resistant strains are shown. It takes at least four sequential steps with one mutation becoming established in the population before another one occurs.

None of the mutations occurred simultaneously as Behe claimed in his book.

The intelligent design creationists are somehow still crowing victory. I don’t quite understand how — their premises have been demolished, they’ve been cut off at the knees, but I guess their followers are easily bamboozled if they shout “math!” loud enough. Even if the math is wrong.

Friday Cephalopod: They’re forming tribes!

social-octopus_sm

We’re doomed. The Pacific striped octopus is exhibiting complex social behaviors.

Panamanian biologist Aradio Rodaniche first reported the Pacific striped octopus in 1991 off the coast of Nicaragua, noting its strange behavior—living in groups of possibly up to 40, laying multiple egg clutches, and mating face-to-face and sucker-to-sucker. Most other octopus species, for instance, come together only to mate.

Next thing you know, they’re making spears, forming hunting parties, warring with one another. And then they develop city-states, philosophy, diplomacy, and politics, and all the horrible appurtenances thereof: assassins, lobbyists, and televangelists. Then they take over.

It’s all because of that face-to-face mating. Hey, that’s our thing! They’re copying our specialty! Only they’re making it scarier.

"Regular octopus mating, where the male is behind and on top of the [female]—or far away—that’s scary enough to watch," said Ross. Females of many species, for instance, will sometimes kill and eat their mate, even if they are mating from a distance.

But "watching these guys come and interact with their beaks—wrapped up in a ball of limbs—are they fighting or mating?" he recalled wondering.

OK. They win.

Inhofe is wasting our time

Minnesota’s Democratic senator, Amy Klobuchar, recently introduced a resolution in the senate that simply stated a clear fact that congress tries to avoid: that climate change is real. James Inhofe (Republican doofus from Oklahoma) got up to insist that he sees nothing, nothing, and that he had a petition from 9,000 cranks that there’s nothing to worry about.

Then Sheldon Whitehouse of Rhode Island rose up to slap him down.

People like Inhofe are a catastrophe for progress and reasonable action on important issues. Could you Oklahomans please stop electing these idiots? We’re getting rid of Bachmann up here in Minnesota, I think it’s only fair that you sacrifice a wingnut, too.

Scariest news yet

Liberia is experiencing a major Ebola outbreak.

Liberian President Ellen Johnson Sirleaf has announced the closure of most of the Ebola-hit country’s land borders after the deadly tropical virus spread to two of west Africa’s largest cities.

Liberia, along with neighbouring Guinea and Sierra Leone, is struggling to contain an epidemic that has infected some 1,200 people and left at least 670 dead across the region since the start of the year.

A 56% mortality rate is a great improvement over the 90% reported in previous outbreaks, but it’s dependent on getting care to the affected rapidly. And one of the affected is an American doctor working to treat Ebola patients in Monrovia. Even that rate could worsen if the medical infrastructure were to break down.

FOOOBAAAWW vs. Birds

As if it wasn’t enough of an offense that the Minnesota Vikings got buckets of money to build a brand new stadium…now it seems that their soaring glass design for the thing is an invisible wall of death to migrating birds, and they’ve refused to consider using bird-safe glass. I guess it’s going to be one of the unadvertised pleasures of watching the Vikings play, that you’ll get to stroll through scattered feathered corpses on the way in. Or maybe they think it will reduce regional unemployment, because they’ll have to hire people to pick up dead birds and wash blood splatters off the glass.

And it will be a lot of birds. We’re located in the great Midwestern flyway, where migrating birds pass through seasonally, taking advantage of all the lakes and rivers in the area for resting and feeding. Rivers like the Mississippi. Which the stadium is built near.

Look! Bird radar!

birddar

There’s a petition to the owners to use bird-safe design. Everyone should sign it.

The dog is a nice touch

The National Review apparently has an article this month, sneering at nerd culture in general and Neil deGrasse Tyson in particular (I haven’t read it, since it’s behind a paywall). It’s called “Smarter Than Thou”, and I guess Republicans find intelligence repulsive, and an intelligent black man is an affront to nature.

But here’s a very nice counter to the claim that Tyson is some elitist snooty guy: he explains the difference between climate and weather.

I like this hypothesis

But we have to be clear that it is only a hypothesis at this point. I was reading about domestication syndrome (DS) — selecting animals for domestication has a whole collection of secondary traits that come along for the ride, in addition to tameness. We are selecting for animals that tolerate the presence of humans, but in addition, we get these other traits, like floppy ears, patchy coat color, shortened faces, etc.; the best known work in this area is by Belyaev (YouTube documentary to get you up to speed) who selected silver foxes for domesticity, and got friendly foxes who also had all these other differences from their wilder brethren. Similar changes have been seen in rats and mink, so it seems to be a mammalian characteristic that all these differences are somehow linked. Here’s a handy list of the changes in domestication syndrome.

List of traits modified in the “domestication syndrome” in mammals

Trait Animal species Location/source
Depigmentation (especially white patches, brown regions) Mouse, rat, guinea pig, rabbit, dog, cat, fox, mink, ferret, pig, reindeer, sheep, goat, cattle, horse, camel, alpaca, and
guanaco
Cranial and trunk
Floppy ears Rabbit, dog, fox, pig, sheep, goat, cattle, and donkey Cranial
Reduced ears Rat, dog, cat, ferret, camel, alpaca, and guanaco Cranial
Shorter muzzles Mouse, dog, cat, fox, pig, sheep, goat, and cattle Cranial
Smaller teeth Mouse, dog, and pig Cranial
Docility All domesticated species Cranial
Smaller brain or cranial capacity Rat, guinea pig, gerbil, rabbit, pig, sheep, goat, cattle, yak, llama, camel, horse, donkey, ferret, cat, dog, and mink Cranial
Reproductive cycles (more frequent estrous cycles) Mouse, rat, gerbil, dog, cat, fox, goat, and guanaco Cranial and trunk (HPG axis)
Neotenous (juvenile) behavior Mouse, dog, fox, and bonobo Cranial
Curly tails Dog, fox, and pig Trunk

(Hah, reduced brain size. I have a cat, I believe it.)

We have a very good idea of the proximate cause of tameness: the animals have reduced adrenal glands, which means their stress response is reduced, they’re generally less fearful, and they are more open, in early life at least, to socialization. But why can’t genetic mutations that reduce the size of the adrenal gland occur without also changing the floppiness of the ears? There isn’t an obvious physiological link between the two, or other traits in that list.

One idea is that there is a Genetic Regulatory Network (GRN). A GRN is a set of genes that mutually regulate each other’s expression, and may be controlled by the same set of signals. Imagine a lazily wired house in which the lights in the kitchen and the living room are on the same circuit, so you use one switch to turn them both on and off. Or perhaps you’ve cleverly wired in a simple motion sensor, so that when you trip the living room light, the changing shadows concidentally trigger the kitchen light too. Everything is tangled together in interacting patterns of connectivity, so you often get unexpected results from single inputs. The mammalian GRN works, though, so it’s been easier to keep it for a few tens of millions of years, rather than rewiring everything and risking breaking something.

More evidence that there’s a network involved is the fact that these domestication changes can happen incredibly rapidly — Belyaev was getting distinctive behaviors with only decades of selective breeding. What that means is that we’re not dealing with the sudden emergence of mutations of large effect, but with many subtle variations of multiple genes that are being brought together by recombination. This also makes sense. Rather than gross changes that change the entire GRN, what you are doing is tapping into small differences in a number of genes that individually have little or no effect, but together modify the target organ. So in order to change the size of an adrenal gland, you gather together an existing mutation that makes a tiny change in the size while also making ears floppier, and another one that also makes a tiny change in size while also shortening the snout, and another that makes a tiny change while modifying pigment cells.

That’s a very nice general explanation, but in order to advance our understanding we need something a little more specific. What genes? What links all these traits together?

Wilkins and his colleagues have suggested an obvious starting point: it’s all neural crest. Neural crest cells (NCCs) are an early population of migrating cells that infiltrate many tissues in the embryo — they form pigment cells, contribute to craniofacial cartilages, supporting cells for the nervous system, and just generally are found in precisely the places where we see the effects of domestication. So one reasonable hypothesis is that when you’re selecting for domestication, you’re actually selecting for reduced adrenal glands, which is most easily achieved by selecting for retarded or reduced or misdirected NCC migration or increased NCC apoptosis (multiple possible causes!), which has multiple effects.

nceffects

In a nutshell, we suggest that initial selection for tameness leads to reduction of neural-crest-derived tissues of behavioral relevance, via multiple preexisting genetic variants that affect neural crest cell numbers at the final sites, and that this neural crest hypofunction produces, as an unselected byproduct, the morphological changes in pigmentation, jaws, teeth, ears, etc. exhibited in the DS. The hypothesized neural crest cell deficits in the DS could be produced via three routes: reduced numbers of original NCC formed, lesser migratory capabilities of NCC and consequently lower numbers at the final sites, or decreased proliferation of these cells at those sites. We suspect, however, that migration defects are particularly important. In this view, the characteristic DS phenotypes shown in parts of the body that are relatively distant from the sites of NCC origination, such as the face, limb extremities, tail, and belly midline, reflect lower probabilities of NCC reaching those sites in the requisite numbers. The stochastic, individual-to-individual variability in these pigmentation patterns is consistent with this idea.

They document all the phenotypic changes associated with domestication, and strongly correlate them with neural crest mechanisms. It’s a mostly convincing case … my major reservation is that because NCCs are ubiquitous and contribute to so many tissues, it’s a little bit like pointing at a dog and predicting that its features are a product of cells. It’s a very general hypothesis. But then they also discuss experiments, such as neural crest ablations or genetic neurocristopathies that directly modify the same processes involved in domestication syndrome. So it is a bit helpful to narrow the field from “all cells” to “this unique set of cells”.

I have a similar reservation about their list of genes that are candidates for the GRN — they list a lot of very familiar genes (PAX and SOX families, GDNF, RTKs) that are all broadly influential transcription factors and signaling molecules. Again, it helps to have a list of candidates, it’s a starting point, but in an interacting network, I’d be more interested in a summary of connections between them than in scattered points in the genome.

You need a diagram to summarize this hypothesis, and here it is, featuring the important distinction between selected and unselected traits.

ncsummary

I do have one question that wasn’t discussed in the paper, and would be interesting to answer with better genetic data. We talk about domestication syndrome as if it all goes one way: wild predator becomes more tolerant of humans. But it seems to me that it’s a two-way process of selection, and humans also had to be less stressed out and tolerant of sharing a space with an animal that would like to eat them, or compete with them for resources. Are humans self-domesticated apes? Were we selected for reduced neural crest input? If we figured out the changes in genes involved in domestication, it would be cool to look at dogs and cats and foxes, and then turn the lens around and ask if we experienced similar changes in our evolution.


Wilkins AS, Wrangham, RW and Fitch WT (2014) The “Domestication Syndrome” in Mammals: A Unified Explanation Based on Neural Crest Cell Behavior and Genetics. Genetics 197(3):795-808.