Bad idea, putting me on a poll

It’s just a silly online poll, and I don’t have a stake in how it comes out one way or the other, except for one thing: I must defeat Brad Pitt. I like the guy, and I’ve enjoyed his movies, and I’m happy that he’s come out as an atheist, but you know…I’m looking forward to being able to go into the bedroom and tell the Trophy Wife™ that I’m better than Brad Pitt at something. And she will say, “I know, baby, I know,” no matter what, but it would just be nice to have some statistical backing for the claim.

Atheist of the Year 2009

Richard Dawkins
32%
Bill Maher
15%
PZ Myers
17%
Greg Epstein
0%
Margaret Downey
13%
Fred Edwords
6%
Brad Pitt
15%

If you all run over there and push Brad Pitt over the top, at least I’ll still be able to demonstrate my superiority in one area with a graphical demonstration of Pitt’s hideous beards.

Anyway, have fun storming the poll, no matter how you vote!


P.S. I just realized that I have a trump card. Even if he beats me on this poll, I’ve still got a more attractive wife than he does. So go ahead, vote however you want, my ego is safe.

Shame on Italy

This is absurd. The Italian National Research Council is sponsoring the publication of a creationist book, titled Evolutionism: The Decline of an Hypothesis. Right away, from the title alone, you can tell that the book has problems: evolution is not a theory in decline, no matter how much the creationists declare it so, but is guiding a thriving research program. The contents are something else, too: apparently, it declares that dinosaurs went extinct just 40,000 years ago, and that radiometric dating is wrong.

Wow. It’s not just a creationist book, but a young earth creationist book. Right away, we can make some predictions about the author. Roberto de Mattei: that he knows nothing about science, and that he’s a political creature.

Bingo.

De Mattei, a political appointee to CNR, teaches the History of Christianity and the Church at the European University in Rome and is president of the Rome- and Washington, D.C.-based Lepanto Foundation, a Catholic group.

You know, when you sponsor a book that proposes to throw out basic physics, chemistry, and biology, you really ought to make sure the author has some chops in those fields.

We’re very traditional around here

THIS. IS. MINNESOTA. We like our Christmases white around here, and it’s not enough just to have a few decorative snowflakes tumble down — we need a blizzard, and that’s what we’re going to get. I was out there in the frigid whiteness earlier today, clearing the driveway and sidewalks, and now I’m all worn out, ready for a good night’s rest. I expect I’ll get up tomorrow to find even more snow piled up everywhere.

Another traditional way to spend the day before the blizzard is to scurry about stocking the larder, and I did a bit of that too…which led to the nicest, sweetest, most heart-warming occurrence. I was listening to the radio, and the announcer came on to mention the coming major snowstorm, and then — O Christmas Joy — began to read off a long, long list of church closures, religious programs cancelled, and Christian events shut down. It was like the Atheist Rapture had come. I felt my heart grow two sizes, and it wasn’t just congestive heart failure brought on by over-exertion.

One more traditional affair to take care of: when I was a young’un in Seattle, on Christmas eve we’d watch the television clown, J.P. Patches, who would always have a little conversation with Santa. It’s not quite Santa, but they’re pretty much the same thing: tonight, from 9-11 Central time, you can tune in to Pacifica radio 90.1 in Houston, Texas, and listen to Scooter chatting with Jesus! Oh, that will make the conservatives so happy, that liberal radio jettisons the secular icon of Santa Claus and goes straight to the founder of their faith. It’s going to be a great Christmas program, and it should be unperturbed by our upper Midwestern blizzard.

Now you may be thinking, “But I’m not in Texas!” This, of course, is yet another reason to praise Jesus. You’re also in luck, because Jesus will be streaming over the interwebs. You can also call in to 713 526 5738 and speak to Jesus — maybe you can tell him what toys you want.

I understood there will also be a Hell Pope of the Subgenius on, so all theological issues will be thoroughly covered.

The reason for the season!

It’s Christmas Eve. You’re probably all busy with holiday preparations, getting together with family, making the traditional dinner, all that secular stuff that makes the day worth celebrating. I know that in the midst of this hustle and bustle you already don’t believe in Santa Claus, but I’m going to ask you to take a quiet, contemplative moment to think about the roots of this day, and don’t believe in Jesus, too.

I know, I’m agreeing with all those crazy Bill O’Reillys and Donald Wildmons and other shrill Christian combatants in the war on Christmas who demand that you acknowledge the “holy” in holiday, but it’s true: the midwinter seasonal holiday was created by people with the superstitious belief that supernatural transitions accompanied natural ones, and these few days are traditionally special because of a belief in their magical importance, and every religion attaches some godly event to the solstice season. It’s why you’ll get a day off on Christmas, which means it was good for something. So just pause, bow your head, and think about Jesus. And reject him.

Also consider God, the Holy Ghost, all the prophets and saints, the angels and demons, the Great Old Ones, any pantheon ever erected in heaven, all the ghosts and boojums, and deny them, every one. Think about all the pious, sanctimonious god-bothers who tell you to worship their dead gods on this day, and tell them, “No.”

You’re free.

Feels good, doesn’t it? Remember the reason for the season, and be sure to go “Ho ho ho!” at it now and then, and let laughter fill your home.

War on Christmas, continued

There is a sign among the various holiday displays at the Illinois state capitol, set there by the Freedom from Religion Foundation.

At the time of the winter solstice, let reason prevail. There are no gods, no devils, no angels, no heaven or hell. There is only our natural world. Religion is just myth and superstition that hardens hearts and enslaves minds.

I like it, but then I would. Somebody else didn’t like it, which is his right, of course…but what he doesn’t have the right to do is to try and tear the sign down. William Kelly, who is also a candidate for state comptroller (he got his cheap publicity), has the standard cowardly excuse: think of the children!

The fact that sign was immediately in front of the tree, I found that to be disturbing because any family and any child would run up to that tree with a smile on their face, and they would immediately see that sign.

Hide the wimminfolk and babies! There’s atheists in Springfield!

I find nativity scenes to be disturbing. Am I therefore justified in smashing them with a hammer? I rather doubt that Kelly will be able to comprehend the equivalence of that situation.

Spotting the black hats among the climate change denialists

Jim Lippard has put up an excellent post identifying the major institutions behind climate change denial. They are almost uniformly conservative and populated with old and unqualified cranks, although Jim is too genteel to put it that way. It’s useful information if you need a scorecard to keep track of the players.

It’s also amusing. Lippard makes this passing mention of a certain notorious crank in a discussion of the denialists with the best academic credentials:

The top-cited scientist, Lubos Motl, has 150 citations for his fourth-most-cited paper, but he’s a theoretical physicist with no publications containing the word “climate.”

Lubos Motl replies!

Commie,

I urge you to instantly remove the libels and lies from this blog, otherwise I will start to work on the legal liquidation of the criminal that you are.

These things may be common among the green trash in which you seem to live but I won’t tolerate it against myself.

Wow. “Legal liquidation.” I’m impressed. Although…did anyone spot any lies or libels against Motl? Does he have 151 citations for that paper, or what?

If you hadn’t realized that Motl is a freakish little sociopath before, that comment may just persuade you.

α-actinin evolution in humans

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Perhaps your idea of the traditional holiday week involves lounging about with a full belly watching football — not me, though. I think if I did, I’d be eyeing those muscular fellows with thoughts of muscle biopsies and analyses of the frequency of α-actinin variants in their population vs. the population of national recliner inhabitants. I’m sure there’s an interesting story there.

In case you’re wondering what α-actinin is, it’s a cytoskeletal protein that’s important in anchoring and coordinating the thin filaments of actin that criss-cross throughout your cells. It’s very important in muscle, where it’s localized in the Z-disk at the boundaries of sarcomeres, the repeated contractile units of the muscle. This diagram might help you visualize it:

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Actin (green), myosin (red). Rod-like tropomyosin molecules (black lines). Thin filaments in muscle sarcomeres are anchored at the Z-disk by the cross-linking protein α-actinin (gold) and are capped by CapZ (pink squares). The thin-filament pointed ends terminate within the A band, are capped by tropomodulin (bright red). Myosin-binding-protein C (MyBP-C; yellow transverse lines).

The most prominent elements in the picture are the thin filaments (made of actin) and thick filaments (made of myosin) which slide past each other, driven by motor proteins, to cause contraction and relaxation of the muscle. The α-actinin proteins are the subtle orange lines in the Z disks on the left and right.

The α-actinin proteins are evolutionarily interesting. In vertebrates, there are usually four different kinds: α-actinin 1, 2, 3, and 4. 1 and 4 are ubiquitous in all cells, since all cells have a cytoskeleton, and the α-actinins are important in anchoring the cytoskeleton. α-actinin-2 and -3 are the ones of interest here, because they are specifically muscle actinins. α-actinin-2 is found in all skeletal muscle fibers, cardiac muscle, and also in the brain (no, not muscle in the brain, there isn’t any: in the cytoskeleton of neurons). Just to complicate matters a bit, α-actinin-2 is also differently spliced in different tissues, producing a couple of isoforms from a single gene. α-actinin-3 is not found in the brain or heart, but only in skeletal muscle and specifically in type II fast glycolytic muscle fibers.

Muscle fibers are specialized. Some are small diameter, well vascularized, relatively slow fibers that are optimized for endurance; they can keep contracting over and over again for long periods of time. These are the fibers that make up the dark meat in your Christmas turkey or duck. Other fibers are large diameter, operate effectively anaerobically, and are optimized for generating lots of force rapidly, but they tend to fatigue quickly — and there are more of these in the white meat of your Christmas bird. (There are also intermediate fiber types that we won’t consider here.) Just keep these straight in your head to follow along: the fast type II muscle fibers are the ones that you use to generate explosive bursts of force, and may be enriched in α-actinin-3; the slower fibers are the ones you use to keep going when you run marathons, and contain α-actinin-2. (There are other even more important differences between fast and slow fibers, especially in myosin variants, so differences in α-actinins are not major determinants of muscle type.)

Wait, what about evolution? It turns out that invertebrates only have one kind of α-actinin, and vertebrates made their suite of four in the process of a pair of whole genome duplications. We made α-actinin-2 and -3 in a duplication event roughly 250-300 million years ago, at which time they would have been simple duplicates of each other, but they have diverged since then, producing subtle (and not entirely understood) functional differences from one another, in addition to acquiring different sites of expression. α-actinin-2 and -3 in humans are now about 80% identical in amino acid sequence. What has happened in these two genes is consistent with what we know about patterns of duplication and divergence.

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Using sarcomeric α-actinin as an example, after duplication of a gene capable of multiple interactions/functions, there are two possible distinct scenarios besides gene loss. A: Sub-functionalisation, where one interaction site is optimised in each of the copies. B: Neo-functionalisation, where one copy retains the ancestral inter- action sites while the other is free to evolve new interaction sites.

So what we’re seeing in the vertebrate lineage is a conserved pattern of specialization of α-actinin-3 to work with fast muscle fibers — it’s a factor in enhancing performance in the specific task of generating force. The α-actinin-3 gene is an example of a duplicated gene becoming increasingly specialized for a particular role, with both changes in the amino acid sequence that promoted a more specialized activity, and changes in the regulatory region of the gene so that it was only switched on in appropriate muscle fibers.

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Duplication and divergence model proposed by this paper. Before duplication the ancestral sarcomeric α-actinin had the functions of both ACTN2 and ACTN3 in terms of tissue expression and functional isoforms. After duplication, ACTN2 has conserved most of the functions of the preduplicated gene, while ACTN3 has lost many of these functions, which may have allowed it to optimise function in fast fibres.

That’s cool, but what we need is an experiment: we need to knock out the gene and see what happens. Mutations in α-actinin-2 are bad—they cause a cardiomyopathy. Losing α-actinin-4 leads to serious kidney defects (that gene is expressed in kidney tissue). What happens if we lose α-actinin-3?

It turns out you may be a guinea pig in that great experiment. Humans acquired a mutation in the α-actinin-3 gene, called R577X, approximately 40-60,000 years ago, and this mutation is incredibly common: about 50% of individuals of European and Asian descent carry it, and about 10% of individuals from African populations. Furthermore, an analysis of the flanking DNA shows relatively little recombination or polymorphism — which implies that the allele has reached this high frequency relatively recently and rapidly, which in turn implies that there has been positive selection for a nonsense mutation that destroys α-actinin-3 in us. The data suggests that a selective sweep for this variant began in Asia about 33,000 years ago, and in Europe about 15,000 years ago.

There is no disease associated with the loss of α-actinin-3. It seems that α-actinin-2 steps up to the plate and fills the role in type II fast muscle fibers, so everything functions just fine. Except…well, there is an interesting statistical effect.

The presence of a functional α-actinin-3 gene is correlated with athletic performance. A study of the frequency of the R577X mutation in athletes and controls found that there is a significant reduction in the frequency of the mutation among sprinters and power-lifters. At the Olympic level, none of the sprinters in the sample (32 individuals) carried the α-actinin-3 deficiency. Among Olympic power lifters, all had at least one functional copy of α-actinin-3.

Awesome. Now I’m wondering about my α-actinin-3 genotype, and whether I have a good biological excuse for why I always got picked last for team sports in high school gym class. This is also why I’m interested in taking biopsies of football players…both for satisfying a scientific curiosity, and for revenge.

You may be wondering at this point about something: α-actinin-3 has a clear beneficial effect in enhancing athletic performance, and its conservation in other animal species suggests that it’s almost certainly a good and useful protein. So why has there been positive selection (probably) for a knock-out mutation in the human lineage?

There is a weak correlation in that study of athletic performance that high-ranking athletes in endurance sports have an increased frequency of the R577X genotype; it was only seen in female long-distance runners, though. More persuasive is the observation that α-actinin-3 knockouts in mice also produced a shift in metabolic enzyme markers that are indicative of increased endurance capacity. The positive advantage of losing α-actinin-3 may be more efficient aerobic metabolism in muscles, at the expense of sacrificing some strength at the high end of athletic performance.

This is yet another example of human evolution in progress—we’re seeing a shift in human muscle function over the course of a few tens of thousands of years.


Lek M, Quinlan KG, North KN (2009) The evolution of skeletal muscle performance: gene duplication and divergence of human sarcomeric alpha-actinins. Bioessays 32(1):17-25. [Epub ahead of print]

MacArthur DG, Seto JT, Raftery JM, Quinlan KG, Huttley GA, Hook JW, Lemckert FA, Kee AJ, Edwards MR, Berman Y, Hardeman EC, Gunning PW, Easteal S, Yang N, North KN (2007) Loss of ACTN3 gene function alters mouse muscle metabolism and shows evidence of positive selection in humans. Nat Genet.39(10):1261-5.

Yang N, MacArthur DG, Gulbin JP, Hahn AG, Beggs AH, Easteal S, North K (2003) ACTN3 genotype is associated with human elite athletic performance. Am J Hum Genet 73(3):627-31.

Teaching Your Inner Fish

Next Fall, I’ll be back in the classroom teaching introductory biology again. One thing I’m planning to do is to use Shubin’s Your Inner Fish for that course…and just look what the good man has done just for me: all the figures from the book have been released as powerpoint slides.

OK, he probably didn’t think about me at all, and he’s releasing them for everyone to use, but still…it’s awfully serendipitous.

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Grab ’em all, teachers! These are tools for getting more evolution into the biology classroom!