Category Archives: biology

Parthenogenesis: now in snakes!

So, as if my friends on the religious right needed more reasons to be afraid of snakes, now they are threatening to undermine the nuclear family, which is clearly defined in the Bible as a mommy, a daddy, and two overachieving children. A recent paper in Biology Letters has studied two litters of offspring from a female Boa constrictor, totaling 22 baby snakes. All of the babies are female, and all of them have a rare, recessive color trait that is exhibited by the mother, but by none of the possible fathers.

What the researchers were able to demonstrate was that these baby snakes do not have a father at all. Rather, they are all parthenogenetic products of the mother. The researchers typed the offspring at eight microsatellite loci, and all the daughters were homozygous at all of the loci, matching in each case one of the two maternal alleles.

Note to self: No Boa constrictors on the island!

Several interesting things here. First, the implication is that these daughters are genome-wide homozygotes. This suggests a complete absence of lethal recessive mutations in the mother’s genome. This seems surprising, but let’s do a quick back of the envelope calculation. Let’s assume there are about 10,000 genes in the snake where a loss-of-function mutation is lethal. Say the coding region for each gene is about 1000 nucleotides long, and that, say 1/10 of those nucleotides are fixed, in the sense that a mutation obliterates the gene’s function. That would be a lethal mutational target of 100 nucleotides for each gene. Assuming a mutation rate of 10-9, mutation-selection balance at each locus would have loss-of-function mutations circulating at a frequency of about 1 in 3000. So, we would expect each maternal half-genome to contain, on average, about 3 lethal recessive mutations. Assuming that those mutations are Poisson distributed, there is about a 5% chance that it would contain no such mutations. So, not super likely, but not out of the question either. And, that probability would be higher if the mutational target is smaller, or if the Boa population has undergone significant inbreeding, which would have driven the frequency down.

Second, there’s a weirdness with the sex chromosomes. Now, in mammals, sex is determined by whether you have two X chromosomes, in which case you are a female, or an X chromosome and a Y chromosome, in which case you are a male. Everyone inherits an X chromosome from their mother, and you inherit either an X or a Y from your father. So, if you don’t have any sons, it’s not your wife’s fault. Snakes also have chromosomal sex determination, but use a ZW system. Males have two Z chromosomes, while females have a W and a Z. It turns out that every one of the parthenogenetic daughter snakes is actually WW. That’s some serious weirdness on which I have little insight. The one thing we can say is that you would never see a YY male. The Y chromosome is a shriveled little thing that does not do much other than tell you to be male, while the X does all the work. The snake W chromosome, on the other hand, is a real chromosome, that is, in fact, impossible to distinguish from the Z under the microscope.

Finally – and this is the reason I’m writing about this here – this tells us something about genomic imprinting. In mammals, there appear to be at least 50-100, possibly as many as 1000 imprinted genes, which are expressed from only one of the two copies. So, if there are 200 imprinted genes, there will be, say, 100 of them that are expressed only from the paternally inherited copy. If you produce parthenogenetic offspring, they will inherit two maternally derived alleles at each of these loci, which will be like having 100 of your genes knocked out, and is almost guaranteed to be lethal. In fact there are a number of genetic disorders in humans that result from uniparental inheritance of just a small subset of imprinted genes, and these produce fairly severe phenotypes. So, the fact that these parthenogenetic snakes appear to be perfectly viable implies that there are few – or quite possibly no – imprinted genes in this species.

Booth, W., Johnson, D., Moore, S., Schal, C., & Vargo, E. (2010). Evidence for viable, non-clonal but fatherless Boa constrictors Biology Letters DOI: 10.1098/rsbl.2010.0793

Update: Two follow-up posts here and here.

The flux capacitor in your brain

So, you already know that Friday was the 55th anniversary of Doc Emmett Brown’s falling off his toilet, hitting his head, falling unconscious, and coming up with the flux capacitor, which not only allowed Teen Wolf to make out with Caroline in the City, but is singlehandedly responsible for the fact that anyone still remembers what a DeLorean is. How do I know you know? Because you spent all week baking this cake.

It took the good doctor thirty more years to get his idea working, so that time travel first became practical in 1985. However, it turns out that, as usual, natural selection got there first. There is an article in press in the Journal of Personality and Social Psychology that presents experimental evidence for precognition or time-reversed instances of causation. The preprint is available here, from the website of the author, Daryl Bem.

Bem is fairly well known, particularly for his early work in social psychology on the “self-perception theory of attitude change,” which is basically that we learn about ourselves in much the same way that someone else might. For instance, say I hate peanut butter sandwiches. But then I eat a peanut butter sandwich every day for a month. I then look at myself, and say, “Hey, that handsome fellow really seems to like peanut butter sandwiches.” This is the academic basis of that damn Stuart Smalley sketch. He is also responsible for the “Exotic becomes erotic” theory of the formation of sexual orientation.

The paper presents the results of nine experiments, each of which tested for awareness of future events. In the first experiment, subjects were told that there was a picture behind one of two (virtual) curtains, and they were supposed to guess which one. When the picture was just a picture, they picked the right curtain 49.8% of the time, which was not significantly different from the expected 1/2. But, when it was an EROTIC picture, they picked the right picture 53.1% of the time, which, while not particularly overwhelming, is apparently statistically significant at the p=0.011 level. There are eight more experiments on retroactive priming, precognitive avoidance of negative stimuli, and retroactive habituation and induction of boredom. The article also includes discussions of random number generators, pseudorandom number generators, quantum mechanics, and Alice in Wonderland.

So, if you read to the end of this blog post in the hopes that I would tell you what the hell is going on here, I’m afraid I’m going to leave you disappointed. Although, to be fair, your precognitive boredom should have known that I would have nothing intelligent to say sometime around the slash-fic link, in which case you’ve long since moved on. I’ll just lay out the obvious candidates. First, it’s pure chance, although getting consistent results across nine experiments makes this seem not terribly likely. Second, these are nine of a much larger number of experiments, most of which did not conform with the experimenter’s expectations, and were therefore viewed as flawed and discarded. Third, there is actual manipulation of the experiments and/or data, either consciously or unconsciously. Fourth, there is some small possibility of some crazy-cool, Dune-esque, Jedi stuff going on here that is someday going to completely revolutionize how we understand cognition, causation, and time.

Personally, my money is on some combination of options two and three. Even without any type of fraud going on, I think it is incredibly easy for us as scientists to be so convinced that we know what the outcome of an experiment is going to be, that we can massage things around the margins. Keep in mind that these effects are only a couple of percent. On the other hand, even the smallest possibility of number for justifies, to me, the entire institution of tenure. This is exactly the sort of nut-bag research program that you can only pursue if you have absolute job security. I wish that more tenured faculty pursued research like this.

Democrats investing in kleenex, socks in wake of midterm elections

So, yesterday’s election turned out rather poorly for Democrats.

On a completely unrelated note, I wanted to draw attention to a paper published in Biology Letters that investigates the ejaculatory strategies of male flour beetles of the species Gnatocerus cornutus. As in many species, G. cornutus males engage in pre-copulatory sexual selection, where males fight, and the winners get privileged access to mates. The researchers, at Okayama University, find that the losers of these fights appear to shift to a strategy that focuses more on sperm competition, through increased “ejaculatory investment.” Winning a fight has no effect on the number of sperm “transferred” during a copulatory event. However, losers show two effects that indicate a strategic shift: they are less aggressive towards other males, and they increase their sperm transfer by nearly two-fold.

By the fifth day after losing the fight, both aggressiveness and sperm-transfer levels return to normal, so we can expect a return to Republican levels of “transfer” sometime this weekend.

Genomic Imprinting II: Inclusive Fitness and Conflict

So, as we discussed previously, genomic imprinting is the phenomenon where the pattern of expression of an allele differs depending on whether that allele was inherited from your mother or your father. This difference in expression does not depend on differences in the DNA sequence of the two alleles. Your two alleles might have identical DNA sequences, but function completely differently.

For example, one of the two alleles might be epigenetically silenced. That is, because of reversible chemical modifications to the DNA, or to proteins that are closely associated with the DNA, that allele would be inactive. The other allele, with an identical DNA sequence, but different modifications, would be happily chugging along producing its gene product(s). Today’s question is, “That seems crazy! Why would you do something like that?”

One of interesting (and by “interesting” I mean “sad”) things about evolutionary biologists is that whenever something genuinely new and surprising is found in the world, everyone feels the need to propose an evolutionary explanation for it, whether new explanations are needed or not. So, many attempts to explain the origins of imprinting have been proposed, most of which are consistent with at least some of the data, and a few of which actually make sense. There is one explanation, however, that is far and away the most successful in explaining the distribution and nature of imprinted genes: the “Kinship” or “conflict” theory of imprinting. This theory owes its creation and early development primarily to David Haig (who laid out the theory originally in papers with Mark Westoby and Tom Moore).

The basic idea of the Kinship Theory is that natural selection favors different expression behaviors for maternally and paternally inherited alleles. That is, the optimal level of expression for an allele that is maternally inherited is different from the optimal level for a paternally inherited allele. Now, if you think about that for a minute, it probably seems strange. I mean, if I survive and reproduce, that’s equally good for any of my genes, independent of where I got them from, right? Right?

The key is recognizing that natural selection favors allele that pass on the largest number of copies to future generations. (“Isn’t that what I just said?”) AND, that it doesn’t matter whether those copies are passed on directly by my having children, or if they are passed on because because one of my relatives, who has inherited an identical copy of that allele, has children. There are different ways to represent this (which are all mathematically equivalent if you do them right), but the one that I find most intuitive is the idea of “inclusive fitness.” Basically, we can think of natural selection as maximizing the inclusive fitness of an allele, which is the fitness of every individual in the population, weighted by the probability that they carry the allele. In the simplest model, this probability is 1 for me, 1/2 for a sibling, 1/8 for a cousin, and so on.

Now, think about your relatives. With the exception of your descendants, your full siblings, and their descendants, all of your relatives are related to you either through your mother or your father. That means that, in general, this inclusive fitness calculation will be different for maternally and paternally derived alleles. Therefore, there will be a conflict, where the phenotype that would maximize the inclusive fitness of your maternally inherited allele will be different from the one that would maximize the inclusive fitness of your paternally inherited allele. If this difference is large enough, it can actually drive alleles to take on two different conditional expression strategies, and, voila, imprinting.

Granted, even in the most extreme cases, this difference is likely to be pretty subtle, which might make it seem strange that this could explain a situation where one of the two alleles is completely turned off, while the other one is cranking away. This phenomenon, where a little conflict leads to a big effect, will be the subject of the next installment.

On sex and singles

So, the post title is clearly designed to pump up pageviews, but those of you who have come here hoping to see photos of me with dollar bills hanging out of my G-string are going to be sadly disappointed. The good news is the money you’ll save having your corneas scraped.

This post is actually about the evolution of sex, or “recombination,” as the biologists like to call it. The question is, why does sex exist? Or, at a genetic level, why would an organism do something that passes on only half of its genes (by mating with something that donates another half), rather than simply making a genetic copy of itself. This is often referred to as the “two-fold cost of sex.” Presumably, there must be an evolutionary benefit to sex that is great enough to overcome this two-fold cost.

As with everything in evolutionary biology, there are an enormous number of theories that have been proposed to explain the evolution of sex, but there are two major arguments. One is that sex allows beneficial mutations that arise on different backgrounds to be recombined onto a single genetic background. This allows adaptive evolution to occur at a faster rate. The other (which is really sort of another side of the same coin) is that sex permits more efficient purging of deleterious mutations.

Let me use an analogy that requires us to take a walk down memory lane. You kids may not know this, but a long time ago, music came on albums, which contained a bunch of songs. The problem with the album system was that most bands would put out one good song, and then fill the rest of their album up with crap. So, to get a collection of good songs, you had to buy a whole bunch of other songs that you didn’t actually want. Sure, you could buy the 45, but who did that, seriously?

So, in this analogy, the first theory, the one about beneficial mutations, is like how you would take all of your albums and put the best songs together on a mix tape that you give to a girl you’re trying to impress. Yes, back then, this was done non-ironically by people who were not hipsters. She would then listen to the first few songs out of a sense of politeness, make some awkward comment about how knowledgeable you are, and then mysteriously change her phone number.

One of the great things about the advent of mp3s and digital music sales is that it is easier to hide your embarrassing musical taste. It used to be that your friends would always pull out your Night Ranger album and make fun of you. Now you can rock out to Ke$ha and just close your computer when someone knocks on your office door.

Also, and more relevantly, it is easier and more natural now to buy individual songs. So, you don’t ever wind up owning a whole pile of non-I’m-Gonna-Be-(500-Miles) Proclaimers songs. Music has undergone a transition to where it is more like our second theory, where recombination permits the elimination (through failure to purchase) of deleterious mu(sic)tations.

I’d write more, but there’s a pile of cash on the dresser that I need to count.

On evolution and sequels

So, there are a lot of things in evolution that seem like they are moving in one direction, when actually they are moving the opposite way. Or maybe it’s the other way around – I forget. For instance, one of the things that we know is that the vast majority of naturally occurring mutations are deleterious. That is, just like your crotchety old grandfather always said, children are, on average, a little bit worse than their parents (and the music they listen to is A LOT worse). Yet, somehow, evolution is able to maintain a level of function in the face of these deleterious mutations, and even to create new adaptations.

The reason is natural selection. Children will be worse than their parents on average, but there will be variation. Some will be a lot worse, and some only a little worse. Some may even be a bit better. The key is that the better children will, on average, produce more grandchildren than the worse children will (so your nagging mother was also right). It’s a bit like walking the wrong way on one of those people-movers at the airport.

Of course, there is also noise in the system. Sometimes a big rock falls on the “fittest” individual in a way that has little to do with that individual’s genotype. And sometimes an individual carrying a lot of deleterious mutations starts a polygamous cult and has about a hundred kids. But on average, the filtering effects of selection seem to counterbalance, or even outweigh the effect of those deleterious mutations.

This got me wondering if there was maybe something similar going on with movie sequels. The conventional wisdom in most quarters is the movie sequels suck. Sure, there is the occasional Godfather II, but for every one of those, it seems like there are a hundred films that are closer to Highlander II. So, I did a little study [1], in which I compared three classes of films: movies that got sequels, movies that are sequels, and random movies. Two scores from Rotten Tomatoes were collected for each movie: the “tomatometer” score, which is the percentage of reviews of the movie that were positive, and the user score, which is the average rating (out of 10) by users of the site.

The average scores are:

Movies with sequels: 59.2% positive 5.92 average (coincidence, or Illuminati plot?)
Movies that are sequels: 44.8% positive 5.16 average
Random movies: 45.7% positive 5.21 average

So, what’s our conclusion here? Well, it seems like sequels are, on average, pretty darn similar in quality to the random sample of movies. The outlier is the set of movies that get sequels made. So, maybe we think that sequels suck because we tend to mentally compare them with the originals, and, like our high-school sports careers, they fail to live up to expectations. Maybe sequels suck because movies suck, and a sequel is no more or less likely to suck than anything else. Or is there something about sequelness in itself?

We can drill a little deeper by dividing our movies into five quintiles (with ten movies each) based on the tomatometer scores of the originals:

Bottom quintile:
Movies with sequels: 17% positive 3.6 average
Sequels of movies: 15% positive 3.6 average

Second quintile:
Movies with sequels: 45% positive 5.2 average
Sequels of movies: 22% positive 4.0 average

Third quintile:
Movies with sequels: 58% positive 5.9 average
Sequels of movies: 49% positive 5.3 average

Fourth quintile:
Movies with sequels: 82% positive 7.0 average
Sequels of movies: 64% positive 6.1 average

Top quintile:
Movies with sequels: 94% positive 7.9 average
Sequels of movies: 74% positive 6.8 average

What this makes it look like is that there really is something about making a sequel that makes your movie suck more than the original. For the most part, you can expect a 15-20% drop in the number of favorable reviews going from the original to the sequel, even if the sequel was only average to begin with. The one exception is the bottom quintile, where you can expect your sequel to suck just about as much as the original did. This may be a boundary effect, as the average number of positive reviews is bounded at zero. This is the great thing about making “Baby Geniuses 2” is that it is virtually impossible to underperform “Baby Geniuses.” On the other hand, with a tomatometer score dropping from 2% to 0%, the baby geniuses somehow managed it.


[1] Not-very-scientific study methodology:

In order to collect a sample of sequels, I went to Rotten Tomatoes, and searched for “2” and “II,” discarding anything that was obviously not a sequel, or for which there was no rating information available. This yielded a list of 50 movies, including “2 Fast 2 Furious,” but not “Aliens.” For each of these, I got the “tomatometer” score and the average user rating for that movie and for the movie of which it was the sequel.

For the random sample, I went to The Movie Insider, and used their list of January-June 2009 releases. I discarded anything that was a foreign film or documentary that had an initial release date prior to 2009. The rationale here was that if a documentary is shown at film festivals in 2007, and then gets a major theatrical release in 2009, this is not a random movie. It is a movie that has already undergone a fairly intense selection process. In the end, this list had 75 movies in it.

The study was not double-blind or vetted by anyone else, and undoubtedly contains errors in both transcription and judgment. However, hopefully it is close enough for analogic use.

Genomic Imprinting I

So, one of the things that I study is genomic imprinting. What is that, exactly?

Even if you’re not a biologist, you are probably familiar with the fact that, for most of your genes, we carry two different copies, or alleles. You get one of those alleles from your mom, and one from your dad. Those two alleles could be the same (have identical DNA sequences) or different (usually only at a small number of positions within DNA sequence). If they are different, then the consequences of those alleles on your traits, like how tall you are or what color your eyes are, are determined by the dominance relationship between those two alleles. For example, the main allele responsible for red hair (at the MC1R locus) is recessive in relationship to alleles for brown or black hair. So, if you have only one copy of the red-hair allele, you will probably have dark hair. Importantly, in terms of what follows, it does not depend whether the recessive red-hair allele you have came from your mother or father.

If you are a biologist, you already knew all of that, but you may or may not be familiar with imprinted genes. About one percent (or possibly more) of our genes are imprinted. For these genes, it does matter which allele came from your mother and which one came from your father. That’s because imprinted genes retain a chemical memory of which parent they came from, and function differently depending on their parental origin. More specifically, at an imprinted locus, alleles are subjected to epigenetic modifications in the germ lines (ovaries or testes). These epigenetic modifications can be chemical modifications applied directly to the DNA itself, or modifications to proteins that are closely associated with the DNA. These modifications alter how the allele functions, without modifying the DNA sequence itself. The key thing is that, for imprinted genes, the epigenetic modifications that are established in the male germ line are different from those established in the female germ line. So the allele that came from your father will function differently from the allele that came from your mother, even if the DNA sequences are identical.

In the simplest cases, one of the two alleles is inactivated, or turned off. The effect of that gene on a given trait, then, depends only on the active allele. To return to the red-hair example, imagine that the MC1R locus was imprinted (which it is not, as far as we know), and that only the paternally inherited copy was expressed. Now, if you had one copy of the red-hair allele, and one of the more common dark hair allele, you would not necessarily have dark hair. Your hair would be dark if your red-hair allele came from your mom, but if it came from your dad, your hair would be red.

Of course, as with all things in biology, once you start looking at the details, everything becomes a lot messier and more confusing. But, that is the basic gist.

Genomic imprinting was one of the biggest surprises to come out of molecular biology in the past few decades. Both the origins of imprinting of particular genes, and the effect of imprinting on the evolution of those genes, are interesting questions that we will return to in future posts. At some point along the way, we will get deeper into those messy and confusing details.