Category Archives: biology

How to pronounce "Muller’s Ratchet"

So, how would you pronounce the name “Muller”? According to the standard pronunciation rules of American English, it should sound like a word that means “one who mulls,” with the “u” pronounced like the “u” in mullet. Curiously, however, when evolutionary biologists talk about “Muller’s ratchet,” more often than not they will pronounce the name so that it rhymes with “Bueller,” as in “Hermann Mueller’s Day Off.”

[Aside: Muller’s ratchet refers to a model in which deleterious mutations arise in a population, but there are no beneficial mutations. An individual’s fitness is a decreasing function of the number of deleterious mutations they possess. These deleterious mutations are held in check by purifying selection, such that there is a steady-state distribution of the population into fitness classes. The “ratchet” part refers to the fact that, in a finite population, stochastic fluctuations will eventually lead to the loss of the highest fitness class. The whole distribution then shifts down. This progresses in a ratchet-like fashion, and the fitness of the whole population declines over time. The take-home point is that purifying selection alone is not sufficient to preserve adaptation indefinitely. You also need some number of beneficial mutations to maintain fitness in the long run. Recombination can reconstitute higher fitness classes, reversing the ratchet in the short term, but still leaves the system susceptible to the stochastic fixation of deleterious mutations.]

If you ask one of these evolutionary biologists why they pronounce “Muller” like “Mueller,” they will often point you towards the umlaut on the u (or, somewhat equivalently, the e following the u). The thing is, there is no umalut, nor is there an e. Sometimes they will point to the fact that Muller was German, and that therefore, you know, it should sound more German. Except for the fact that Muller was not German. He was born in New York City. His parents were also born in the United States.

Now, according to Wikipedia:

H. J. Muller and science fiction writer Ursula Le Guin were second cousins; his father (Hermann J. Muller Sr.) and her father’s mother (Johanna Muller Kroeber) were siblings, the children of Nicholas Müller who immigrated to the United States in 1848.

That’s sort of cool about Ursula Le Guin. It also suggests that Muller’s grandfather was, in fact, named “Müller,” which would not really be pronounced the way that people say “Mewler,” but that would at least be the more standard Americanization of the name. What it looks like is that Muller’s grandfather changed his name (either by choice, or by orthographical fiat, as was often the case at Ellis Island). It would not surprise me if he pronounced it in the German fashion, but that the name became fully Anglicized over the course of the next couple of generations.

Of course, with names, I figure the rule is that the correct pronunciation is always how the person themselves pronounces (or, in this case, pronounced) it. On that point, all I can do is point to a seminar by Matt Meselson that I once attended. At the end of his talk, someone from the audience asked a question about “mewler’s ratchet.” Before answering, Meselson made the point that he had known Muller, and the Muller had pronounced it “Muller.” I have attempted to contact Muller’s surviving daughter for more direct confirmation, but have not heard anything back yet. If and when I do, I’ll post an update.

In the meantime, here’s a little mnemonic I’ve whipped up for you

There was once a professor named Muller
whose breakfast could not have been duller.
As his fitness crept down
with a ratcheting sound,
he said, “Man, I could go for a cruller!”

NB: I have also found no evidence that Muller ever lived in Nantucket.

FDA Recommends more Judicious use of Antibiotics in Agriculture

So, the FDA recently put out its report recommending that the agriculture industry reduce its use of antibiotics. Specifically, they urge that the use of antibiotics that are also used to treat humans be used more “judiciously.”

There are two specific widespread practices that the FDA aims to discourage: 1) the use of antibiotics to make animals gain weight faster, and 2) prophylactic use of antibiotics to prevent the outbreak of a disease, even in the absence of any indication that such an outbreak is likely. Both of these are commonly achieved by feeding animals a constant, low dose of antibiotics in their feed or water. This constant-low-dose scheme is, of course, optimal, assuming that your goal is to maximize the rate at which bacteria acquire antibiotic resistance.

As per the FDA’s website, the plan is this: “implementing a voluntary strategy to promote the judicious use in food-producing animals of antibiotics that are important in treating humans,” which basically means leaving it up to the food producers themselves. So, you can fully expect that absolutely nothing will happen, and that you will still die a very slow, painful death from a virulent antibiotic-resistant bacterial infection.

Nature Reviews Microbiology has just published an editorial on the topic in which they point out that these steps by the FDA are not nearly enough, and they provide this depressing tidbit:

In 1977 the FDA began a process which could have resulted in a similar ban to that seen in the EU, by issuing notice of their intention to hold hearings into the withdrawal of approval for the use of penicillin and tetracycline in animals. However, these hearings never took place, and in December 2011 the agency announced that these notices had been formally withdrawn. 

Really, FDA? Are you really that incompetent and corrupt? Don’t answer that, it was a rhetorical question.

Anyway, here’s a strip that appeared last year at Darwin Eats Cake, where Andy and Eleonora debate the use of antibiotics in agriculture. It’s from back before I increased the font size, so it is easier to read on the original site.

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Blue-eyed-people-are-all-related zombie news

So, you know how sometimes at night you’re lying in bed when you burp, but then the burp turns out to actually be you throwing up into your mouth just a little bit, and it tastes like a combination of whatever you ate for dinner and evil? Well, this is sort of like that.

Four years ago, a group of researchers from the University of Copenhagen published a nice paper on the genetics of blue eye color. In that paper they look at a bunch of Danish families in which some people have blue eyes and some have brown eyes (or, combination blue-brown eyes, which, for purposes of this study, are treated as non-blue). They also look at a small sample of non-Danish blue-eyed folks: five from Turkey and two from Jordan.

The paper makes a compelling case that the pure blue eyes phenotype depends on a particular nucleotide substitution that alters regulation of the gene OCA2. Furthermore, there is an extended haplotype around the key mutation that is shared by everyone in their sample (a few people have additional nucleotide substitutions that most likely post-date the key functional mutation). This suggests that, while there are many genes that contribute to eye color variation and to pigmentation in general, there may be a single critical mutation responsible for all of the blue eyes out there. Which is pretty cool.

For reasons that I still don’t understand, this study has popped back into the news recently. In particular, an article that looks to have been written back in 2008 in USA Today was “updated” in February, and has resurfaced on AOL, which describes it as a “study from USA Today,” and warns people with blue eyes about the dangers of falling in love with another blue-eyed beauty. Presumably because of incest (also shown is a clip from HLN — the artist formerly known as CNN Headline News — featuring the anchor doing a whole “ick” thing).

In worst-of-media-coverage-of-science fashion the reports that I have found (both from 2008 and from 2012), coverage focuses on stuff from the paper that is tangential, irrelevant, or wrong.

First, “all blue-eyed people are related.” Where to start. The researchers suggest that the mutation might have arisen 6000-10000 years ago in the Black Sea region, prior to the Neolithic agricultural expansion into Europe. If we assume a generation time of, say, 25 years, that is 240-400 generations. If we look back that far in the past, even just to the 6000 year mark, each of us has 2^240 ancestors. That’s 1.7 x 10^72, which, you will notice, is not just much larger than 7 x 10^9 (the current population of the whole world), but is close to the ballpark of the total number of atoms in the universe.

The fact is, once you go back more than a few hundred years, each of us has a list of ancestors that features the same people over and over again. Not only are we all related, we are all related over and over and over again. While your brother may not be your cousin, your tenth cousin is quite likely to be your seventh cousin as well.

So, yes, all blue-eyed people are related, but there is not really anything here to suggest that they are significantly more closely related than any two people.

Second, both the 6000-10000 year timeframe and the Black Sea origin of the mutation — both of which featured heavily in press coverage of the paper — are completely unsupported by anything in the data. What the authors actually say is this:

The mutations responsible for the blue eye color most likely originate from the neareast area or northwest part of the Black Sea region, where the great agriculture migration to the northern part of Europe took place in the Neolithic periods about 6–10,000 years ago (Cavalli-Sforza et al.1994).

The high frequency of blue-eyed individuals in the Scandinavia and Baltic areas indicates a positive selection for this phenotype (Cavalli-Sforza et al. 1994; Myant et al. 1997). Several theories has been suggested to explain the evolutionary selection for pigmentation traits which include UV expositor causing skin cancer, vitamin D deficiency, and also sexual selection has been mentioned. Natural selection as suggested here makes it difficult to calculate the age of the mutation.

That is, we don’t know how old the mutation is, and have not tried to perform any sort of analysis to ask the question. That’s fine, because what the paper actually does is provide us with a basis for asking these sorts of questions, although that will require more extensive sampling.

The supposition here is based solely on the fact that there was this expansion of agriculture (along with, to a not-fully-characterized extent, an expansion of the genes of the people who developed that early agricultural technology), and that stuff in Europe probably came with that.

The actual way to ask the question would be to go and sequence the DNA of a bunch of folks from all across Europe. To first approximation, we might assume that the mutation first arose in the region where the blue-eyes haplotype shows the greatest within-haplotype genetic diversity. For example, if the mutation first arose near the Black Sea, we should see more genetic variation right around the key mutation among blue-eyed people near the Black Sea. If the allele arrived more recently in Sweden, blue-eyed Swedes would be more genetically similar to each other in the same genomic region, simply because there would have been less time for differences to accumulate.

All else being equal, we might expect the geographical origin of a particular mutation to be at the central point of its range, or near the place where the mutation has reached its highest frequency. That supposition would place the origin somewhere near the Baltic (rather than the Black) Sea. But, there is good reason to believe that this mutation may have been subject to selection. The blue-eyes allele also affects other aspects of pigmentation, and lighter coloring is thought to have been favored at higher latitudes due to the reduced incidence of sunlight.

The fact that we think that natural selection would have pushed the mutation northward means that that its origin was probably somewhere to the South of its current center. Exactly how far depends on a bunch of details, like the strength of selection, and how that strength of selection changes as you move from South to North.

The problem is that, to do it right, you would have to build a model that explicitly incorporates the agricultural expansion and natural selection acting on OCA2, with the strength of selection favoring lighter pigmentation depending on latitude. Maybe also the fact that there are other genes affecting pigmentation. It is something that is doable, especially now that we have a specific gene to focus on, but at this point what we have is a bunch of speculation.

So, to recap, 1) Cool paper. 2) Sex between blue-eyed people is not incest. 3) We have no idea when or where this mutation came from, but it is now conceivable that we could ask the question. 4) Embarrassingly bad science reporting spontaneously rises from the grave four years later and tries to eat your brain.

Eiberg, H., Troelsen, J., Nielsen, M., Mikkelsen, A., Mengel-From, J., Kjaer, K., & Hansen, L. (2008). Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression Human Genetics, 123 (2), 177-187 DOI: 10.1007/s00439-007-0460-x

Ph. Diva and the Mystery Band

So, there are a LOT of lab-life-themed music videos out there. Mostly, they are amateur things put together by groups of under-worked grad students, where they change the lyrics to some popular song, or “pop” song, as the kids say.

This is a whole different thing, with significant production value, which is what happens when a biotech company gets in the game.

It lacks some of the charm and energy of dorky grad students singing Lady Gaga off key. On the other hand, it lacks all of the dorky-grad-students-singing-Lady-Gaga-off-key-ness of dorky grad students singing Lady Gaga off key.

This is actually the second video in a series. The next two will be out later in the year. You can see the prequel here.

Toxoplasmosis Extravaganza: Ride Complete!

So, this week at Darwin Eats Cake, we celebrated our one-year anniversary with a series of nine strips on the zooparasite Toxoplasma gondii. This parasite, which causes Toxoplasmosis, is the reason why pregnant women are encouraged to avoid cat litter.

Here’s the full series, presented for your one-stop-shopping viewing pleasure. The strips do not, I think, assume any expert biological knowledge, so you don’t need to be a parasitologist to enjoy them. However, a dorky and juvenile sense of humor will help a lot. Alternatively, you can read them on the Darwin Eats Cake website, where they look a little better, I think. The series starts at http://www.darwineatscake.com/?id=101.

At this point, Darwin Eats Cake will return to its regular programming schedule, with twice-a-week updates, usually on Mondays and Thursdays, except for those days that have been recognized as official holidays by the Darwin Eats Cake Council of Freeholders and its chairwoman, the duly elected Queen of Naboo.

So, stop by on Monday for a new strip, or any time to trawl the archive: http://www.darwineatscake.com.





It’s Toxoplasmosis week at Darwin Eats Cake

So, tomorrow (March 13) marks the one-year anniversary of the launch of my webcomic Darwin Eats Cake on its very own website (here). Normally, Darwin Eats Cake updates approximately twice a week (hemicircaseptanally), on approximately Monday and Thursday (circa-Mondarily and circa-Thursdarily, I assume). However, to mark this special anniversary occasion, we are rolling out a daily series of strips on Toxoplasma gondii, the parasite responsible for Toxoplasmosis. This bug was recently in the news thanks to a profile of Jaroslav Flegr published recently in the Atlantic (here).

Here are the first two of this week’s six strips:

Best URL for sharing: http://www.darwineatscake.com/?id=101
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Best URL for sharing: http://www.darwineatscake.com/?id=102
Permanent image URL for hotlinking or embedding: http://www.darwineatscake.com/img/comic/102.jpg

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Clarification re: "Hot like Mexico"

So, I just got back from the Colorado School of Mines (And boy are my picks tired!!!), where I was speaking about the Ronin Institute. One of many wonderful things about the trip was the opportunity to meet Alejandro Weinstein, who has been featured twice on Guillaume’s Mailbag over at Darwin Eats Cake. Following a conversation with him, I wanted to clarify something regarding the following strip:

Best URL for sharing: http://www.darwineatscake.com/?id=43
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Alejandro apparently took the third frame of the comic to mean that Guillaume thought that he was from Mexico. I asked Guillaume about this, and he said no, that with a name like “Alejandro Weinstein,” he had assumed that Alejandro was from Argentina. It turns out that Alejandro actually hails from Chile, which is sort of the Argentina of the west coast of South America, so, he wasn’t too far off, really.

Guillaume went on to explain that, actually, “hot like Mexico” and “cool the bad” are references to the lyrics of the Lady Gaga song “Alejandro.” Guillaume had assumed that this was common knowledge, at least until I pointed out to him that the set of people with a high degree of fluency in Lady Gaga lyrics probably shares little overlap with the set of people who read Darwin Eats Cake.
Anyway, Guillaume felt bad about the misunderstanding, and asked me to address it here.
On a related note, Guillaume’s Mailbag is still accepting submissions. Send in any biological trait of any species, and Guillaume will provide an adaptationist explanation for its evolutionary origin. You can reach him at guillaume@darwineatscake.com