Pleiotropy is 100 years old

This year, the term pleiotropy was defined 100 years ago, and Frank Stearns, graduate student at the University of Maryland biology graduate program has written a perspective in Genetics, which I highly recommend.

Looking around umd.edu, I found that Stearn's research topic is "mutations in adaptive landscapes", which explains his interest in pleiotropy. I have the same interest for the same reason (see preprints here and here).

ABSTRACT

Pleiotropy is defined as the phenomenon in which a single locus affects two or more distinct phenotypic traits. The term was formally introduced into the literature by the German geneticist Ludwig Plate in 1910, 100 years ago. Pleiotropy has had an important influence on the fields of physiological and medical genetics as well as on evolutionary biology. Different approaches to the study of pleiotropy have led to incongruence in the way that it is perceived and discussed among researchers in these fields. Furthermore, our understanding of the term has changed quite a bit since 1910, particularly in light of modern molecular data. This review traces the history of the term "pleiotropy" and reevaluates its current place in the field of genetics.

Apparently this Ludwig Plate was a nazi and a misogynist. Sighs. Onward, upward.

Pleiotropy can be caused by one gene making two or more different proteins (alternative splicing) which then affect different traits, or by a single protein affecting multiple traits. The former used to be termed "genuine" pleiotropy, and the latter "spurious" pleiotropy. I'm not so hot on these terms, since the connotation is that there is something less real about pleiotropy caused by a single protein. But no one uses these terms anymore, so never mind. Incidentally, I previously worked with Drosophila gene expression data, and there it was evident that mRNA (which is what gets translated into protein) was found in multiple tissues (we called them domains, but think of them as traits, e.g. 'hind gut', 'glial cells', 'rectum', etc.). Studies mostly confirm that pleiotropy is largely owing to one protein's involvement in several traits, so it doesn't seem so spurious.

Stearns argues that alternative reading frames (where the DNA strand is read at different starting positions, yielding different proteins), which is common in bacteria, is an instance of pleiotropy, since there is information shared between the two 'genes'. I totally concur, since for me the issue is whether a mutation can affect more than one trait, and in this instance it certainly can, given that the different proteins affect different traits.

Current research questions about pleiotropy

One avenue of research on pleiotropy is how extensive it is. Recent research has shot down the assumption of universal pleiotropy made by the founders of the Modern Synthesis (Fisher, Wright, Mayr), which states that all genes has the potential to affect all traits. However, we now know something about the distribution of number of traits affected, i.e., the level of pleiotropy. For example, Wang, Liao, and Zhang (2010) found that in yeast, nematode and mouse, the number of traits that a gene affects ranges between 0 and about 150, with averages of up 5-8 traits for nematode and mouse.



Staerns quotes earlier studies that found the level of pleiotropy to be 4-5 (in yeast, Droshoplia and nematode), 6-7 for eight vertebrate species, and 7.8 for mouse in a study of skeletal genetics.

Since this is counting traits per gene, you may be excused for asking what a trait is (and what a gene is, but that's not my purview). For one thing, the nomenclature is a little confusing. What is meant by trait here, is what is formally known as a character, which is a property of the phenotype. Trait can sometimes mean the value of the character, such as character=hair, trait=brown, but I like to refer to that as the trait value (and I'm not alone). Phenotype can also mean two things, namely the whole physical/biological manifestation of an organism, and that's what I meant here, but it can also refer to a trait, like when they say that knocking out a particular gene causes a particular phenotype. This may all not be very enlightening if we're interested in what a trait is; the pornographic definition seems to be what people apply: "I'll recognize it when I see it". And one may wonder how many traits a species has. The caption to the figure above from Wang et al. reads

Frequency distributions of degree of gene pleiotropy in (A) yeast morphological, (B) yeast environmental, (C) yeast physiological, (D) nematode, and (E) mouse pleiotropy data. Mean and median degrees of pleiotropy and their SDs are indicated. The numbers in parentheses are the mean and median degrees of pleiotropy divided by the total number of traits. After the removal of genes that do not affect any trait and traits that are not affected by any gene, the total numbers of genes and traits in these datasets are (A) 2,449 genes and 253 traits, (B) 774 genes and 22 traits, (C) 1,256 genes and 120 traits, (D) 661 genes and 44 traits, and (E) 4,915 genes and 308 traits.

"Traits that are not affected by any gene..." Strange. Describing the methods they say

Using the yeast morphological pleiotropy data, we calculated the number (n) of traits that are significantly affected by each gene. We then measured a gene’s total phenotypic effect on these n traits, using either the Euclidian distance (TE) or the Manhattan distance (TM).

I'm not sure, but it doesn't seem that even if they looked at all 6,000 yeast genes that they then necessarily identified all traits. Their number of 253 morphological traits... is that enough to completely characterize Baker's yeast? And are 308 really enough to characterize a mouse? How many traits to humans have?

Okay, I'm done. Go.

References:
Stearns, F. (2010). One Hundred Years of Pleiotropy: A Retrospective Genetics, 186 (3), 767-773 DOI: 10.1534/genetics.110.122549
Wang, Z., Liao, B., & Zhang, J. (2010). From the Cover: Genomic patterns of pleiotropy and the evolution of complexity Proceedings of the National Academy of Sciences, 107 (42), 18034-18039 DOI: 10.1073/pnas.1004666107

Historian predicts demise of evolutionary theory

His name is Enézio Eugênio de Almeida Filho, and he is a post-Darwinist. He predicts that evolutionary theory will soon meet its demise, following a grand scale of people recognizing that the evidence does not support it.

Science gave me this conviction. I learned at university, when a scientific theory is not supported by evidence, it must be revised or dropped. I'm post-Darwinian anticipating imminent and impending rupture paradigm in evolutionary biology. Time to say goodbye to Darwin.

This is a Google translation of his Blogger profile - he's Brazilian, and only blogs in Portuguese.

His background is in history of science. He has a PhD in it from 2009, and no apparent background in science at all. The obvious question is "what the hell does he know?" I don't mean to say that he could not know a substantial amount about evolutionary theory, and has a good overview of the evidence. But I doubt it both for the reason that he has no formal education in the natural sciences (doing research about Darwin is not that), which does not really leave one a lot of time to concentrate on the science, and also for the reason that I do know a lot about evolutionary theory through my education and work, and I understand the theory and know the evidence for it (scoop: it's pretty solid).

So, how long are we to wait for this imminent demise? He predicted this formally in 2006: 3. ALMEIDA FILHO, E. E. . An imminent paradigm shift in evolutionary biology?. 2006. (Presentation / Conference or Colloquium). [Via his CV.]

Still waiting...

He just launched a new website, DarwinLeaks. Again, all in Portuguese, which is a hassle. The translation reveals a post asking Why correspondence between Darwin and Mivart has not yet been published online? As far as I can gather, certain letters between Darwin and George Jackson Mivart - who criticized Darwin on scientific grounds (though arguably with a religious motivation) - has not yet been made available to the public. My guess is that de Almeida Filho is very upset about this, as it hinders progress in his own research. But form there to claim that revealing these documents would spell the end of evolutionary theory as we know it... Unconvincing.

Supply and demand doesn't work for universities?

Seems to me Madhusudan is onto something here:

Let me get this straight: we have MORE students enrolling in college, competing to get into overfull classes taught by FEWER faculty every year, and TOO MANY PhDs who would love to have those faculty jobs that are clearly needed to teach all the new students! Does that sound about right? How does this make any kind of economic sense even with a supply-and-demand analysis? Seems to me that the demand is there, as is the supply, yet they aren't exactly meeting up! WTF is that about?!

I can't explain why capitalism is not working in this case. But then, my PhD isn't in economics...

No Santa, no Jesus

Don't dare to miss Ricky Gervais' reasons for being an atheist. I seriously wonder if this stuff is funny for believers, too.

But anyway, there I was happily drawing my hero when my big brother Bob asked, “Why do you believe in God?” Just a simple question. But my mum panicked. “Bob” she said in a tone that I knew meant, “Shut up.” Why was that a bad thing to ask? If there was a God and my faith was strong it didn’t matter what people said.

Oh … hang on. There is no God. He knows it, and she knows it deep down. It was as simple as that. I started thinking about it and asking more questions, and within an hour, I was an atheist.

Wow. No God. If mum had lied to me about God, had she also lied to me about Santa? Yes, of course, but who cares? The gifts kept coming.

As for myself, I've always been an atheist. Even when I chose to be baptized at age ten. But as for Santa, I had a very specific reason never to believe him. In Copenhagen, chimneys are simply too narrow that anyone could get through them. I swear that was the reason.

Why don’t I believe in God? No, no no, why do YOU believe in God? Surely the burden of proof is on the believer. You started all this. If I came up to you and said, “Why don’t you believe I can fly?” You’d say, “Why would I?” I’d reply, “Because it’s a matter of faith”. If I then said, “Prove I can’t fly. Prove I can’t fly see, see, you can’t prove it can you?” You’d probably either walk away, call security or throw me out of the window and shout, ‘’F—ing fly then you lunatic.”

Not possible to absorb alcohol through feet (of course)

Being from Denmark myself, this Danish study caught my eye. It examines what is apparently an urban legend (they call it urban myth, though) in Denmark, namely that one can get drunk by submersing one's feet in alcohol.

I have never heard of this ridiculously credulous idea, but I am not surprised that some idiots were stupid enough to believe it. But wasting vodka in that way...? But then, it's been over a decade since I moved from Denmark.

The researchers tested the hypothesis in a study aptly named the Peace On Earth study, for Percutaneous Ethanol Absorption Could Evoke Ongoing Nationwide Euphoria And Random Tender Hugs. Bravo!

However, they used three bottles of vodka per person, to which I cannot say any bravos. More like, stupid gits!

At this pint it really doesn't seem to matter much what the results were, both because people with half a brain could foresee the outcome, and also because we already know a really good way of getting alcohol into the blood (two*, actually).

And yet, here are the results:

Plasma ethanol concentrations were below the detection limit of 2.2 mmol/L (10 mg/100 mL) throughout the experiment. No significant changes were observed in the intoxication related symptoms, although self confidence and urge to speak increased slightly at the start of the study, probably due to the setup.

The method section is well worth a gander.

Methods
The Peace on Earth study was open labelled and self experimental, with no control group. It evaluated the effect of submerging feet in 2100 mL of vodka (three bottles’ worth) on the concentration of plasma ethanol. Secondary end points were intoxication related symptoms.

Three healthy adults (all authors, CSH, LHF, and PLK) agreed to participate. None had any chronic skin or liver disease or was dependent on alcohol or psychoactive drugs. None was members of local Alcoholics Anonymous communities or had been implicated in serious incidents or socially embarrassing events related to alcohol during the week before the experiment.

Yep, those three participants are the authors of the study. And there's the real clue for us all. There's no reason we cannot combine fun times in the office with research. I've always known this, and yet I've never really been able to get anyone else here in the puritan states to agree to have beer in the office (I have, however, brought beer in a mug to lab meetings, which I highly recommend).

* The other one is the swedish method of inserting a cotton ball dipped in vodka into one's rectum. That REALLY works, and three bottles of vodka is enough for several high schools to go around.

Reference:
Hansen, C., Faerch, L., & Kristensen, P. (2010). Testing the validity of the Danish urban myth that alcohol can be absorbed through feet: open labelled self experimental study BMJ, 341 (dec14 2) DOI: 10.1136/bmj.c6812

Replies to arsenic criticism

An article in The Washington Post describes how Felisa Wolfe-Simon and the team behind the work on arsenic-loving bacteria pushed by NASA are planning to respond to criticism. And indeed, how they have responded as of yesterday. On Felisa's website you can find the FAQ, which I repost here slightly(!) paraphrased:

Some people have questioned whether the DNA was sufficiently cleaned by your technique using gel electrophoresis, to separate it from other molecules. Do you feel this is a valid concern?

(Shorter) Answer: No.

Others have argued that arsenate-linked DNA should have quickly fallen apart when exposed to water. Could you address this?

(Shorter) Answer: No experiments have previously been done relevant to our study.

Is it possible that salts in your growth media could have provided enough trace phosphorus to sustain the bacteria?

(shorter) Answer: We think not.

Is there anything else you’d like for the public to understand about your research, or about the scientific process?

(Hmm, I wonder who asked this question. It's not really one of those very critical questions that this whole debacle included.)

(Shorter) Answer: We love science, and we love you.

I'm not saying that is what the team intended to say in reply to that lat question, but that's the feeling I got from it. Overall, good answers, because they are standing their ground. That means that vindication will be sweet, or that the fall is going to hurt even more. Fun in the blogosphere either which way it goes. And science progresses, but that was never in doubt.

The Washington Post article also includes this bit of cluelessness:

He said that when people launch online attacks on the work done by him and biochemist Felisa Wolfe-Simon, he doesn't really know who is behind them. "I don't want to get involved in what can end up in a Jerry Springer situation, with people throwing chairs," he said.

Oremland is pretty senior, i.e., trained before the advent of the internet. So no wonder. However, practices change, and we must, too. I was trained to write job applications on paper and send it by mail, but (next to) no one does that anymore either. Deal. Also, yes, we do know who is behind much of the serious criticism. Rosie Redfield. George Cody. Steven Benner, surely. The internet is great for looking people up.

But either way they will respond, so all is well on that front.

Yet not only was Oremland on the panel Thursday because of the blogging, but the research team also put out a series of answers to questions frequently asked about their work, and promised to respond by next month to more than 20 letters and e-mails sent to the the magazine Science questioning their work. The team announced as well that it would make samples of the microbes available to other scientists for their research.

Earth, we've got a problem

According to Darryl Cunningham we've got a major problem:



Of course, this isn't merely according to Darryl Cunningham, but rather according to nearly all the scientists who work on this particular problem.

Go see of yourself what it is.

When you get back, we can discuss why it is that people who deny this problem for the reasons given by Darryl, are motivated to do so. I mean, it's not all deniers who are oil-billionaries...

Inside North Korea - true to his behest

Man, I cry for the North Korean people. I look forward to the death of Kim Jong-il, and to the events that will follow (hoping they're not going to be devastating).

Here's a courageously recorded documentary from North Korea by VBS.TV. You should see this fascinating documentary, true to my behest.


(Clip takes you to SnagFilms for the whole video.)

It is chilling to imagine the lives of the people that Shane meets on his secret mission to film inside North Korea. Watching the people in this land of the people, all the time I'm thinking that these aren't even real people, but facades that cover up indoctrinated souls yearning to be free. I imagine a nagging suspicion that they have that the outside world is not that evil, that their lack of food is not necessary (why are the foreigners so well fed?), that laws agains humor are not in their own best interest, etc. etc.

Frozen Evolution book review

Dan Graur reviews Frozen Evolution: Or, That's not the Way It Is, Mr. Darwin: A Farewell to Selfish Gene by Jaroslav Flegr in The Quarterly Review of Biology.

And thank Dan for that, because I know what an awful book that is. As Dan says

I regard this book review as a public service. Life is much too short to waste it on bad books. So, do not even touch this sloppily written, unprofessionally translated, inadequately conceived, improperly edited, dubiously syntaxed, and horribly pompous and tedious stream‐of‐consciousness monologue masquerading as a scholarly work.

I few years back I saw a message somewhere on the web that Flegr was looking for people to review his book, which is in part about epistasis (a topic of my research), so I asked him, and he subsequently sent me a copy. However, I was never able to get through it (apologies), because the writing is indeed sloppy, and the core idea as I perceived it - that because epistasis makes a mutation have different effects on different genetic backgrounds, a mutation can't lead to workable changes in the genome in sexual species, since recombination makes the genetic background in the offspring different from that of both parents - is patently crackpotty. Better things to do, kind of thing.

I have one final piece of advice for those masochists who will imprudently decide against my very strong admonitions to read this book. Have a fun experience by using a “crackpot‐index measure” (see e.g., F. J. Gruenberger. 1964. Science 145:1413–1415) to compare Frozen Evolution against a checklist of the most significant attributes of scientists and quacks. I am looking forward to finding out whether your conclusions will be similar to mine, which I shall keep to myself for the present time.

Mistreating animals for pleasure

For the record, you and I can't be friends if you crush animals for pleasure. It's Julia Galef on Rationally Speaking discussing what the difference is between taking pleasure in acts of violence against animals, and taking pleasure in eating animals that have suffered at the hands of humans with the intent of slaughtering them.

The closest thing that I can find to a morally relevant distinction between industrial farming, dogfighting, and crush videos is this: While it’s true that all three acts cause animal suffering in order to give people pleasure, the nature of that tradeoff differs. The consumers of crush videos and dogfighting are taking pleasure in the suffering itself, whereas the consumers of industrially-farmed meat are taking pleasure in the meat that was produced by the suffering. From a purely harm-based perspective, the moral calculus is the same: the animal suffers so that you can experience pleasure. But the degree of directness of that tradeoff makes a difference in how we perceive your character. Someone whose motive is “I enjoy seeing another creature suffer” seems more evil than someone whose motive is “I want a tasty meal,” even if both people cause the same amount of suffering.

I think Julia's right that the difference to many people will be that the animal suffering of pigs, cows, chicken, etc., is a by-product, and not the main point. But I also think that difference a distraction.

Personally, I'd really very much like if we all ate less meat, and paid more for that meat, with the result that no animals were treated cruelly.

So, we can continue to be friends even if you eat meat of animals who suffered for that, but if you in any way promote suffering of animals because you or someone else take pleasure in that suffering, then you can fuck the right off.

Alligator electrocution

It's really rare that I squirm so much that I have to stop watching something. Here's an alligator attacking an electric eel, and that took me two attempts to finish.



Via Denim and Tweed.

Christopher Maloney doesn't want to be called a quack

I get mail
Category: Kooks
Posted on: December 7, 2010 4:52 PM, by PZ Myers

Some people just don't get it. Christopher Maloney wants to silence a message he doesn't like on the internet by serving a cease & desist order.



The last time I mentioned Maloney was eight months ago, and even then it was to point and laugh at his page throwing crazy paranoid accusations at me. So now, after eight months of neglect, he has decided to stir the pot and remind everyone that Christopher Maloney is a quack and that he keeps on quacking? That makes no sense.

So, once again, the web will start echoing the Christopher Maloney is a quack message.

It must be handy for a quack to marry a lawyer, but I don't think she's giving him good advice in this case. You might as well serve a writ on the tides to stop flowing as ask the internet to erase a piece of its data—your best bet is to allow it to take its course and hope that the wavelet that disturbs you gets lost in the incessant volume.

I'm just quoting, again.

Israel behind Egyptian shark attacks?

This is too funny to be believed, and yet it is not The Onion.

Egyptian Official: Israel Could Be Behind Deadly Shark Attack

An Egyptian official believes that Israel's intelligence agency might be behind the fatal shark attack of a German tourist in Sinai over the weekend, the Jerusalem Post reports.

"What is being said about the Mossad throwing the deadly shark (in the sea) to hit tourism in Egypt is not out of the question, but it needs time to confirm," South Sinai Gov. Muhammad Abdel Fadil Shousha told egynews.net.

Right. Mossad caught a shark, pumped it full of adrenaline, made it smell a pair of swimming pants, and then let it loose near the Egyptian resort. Clever!

Israel is also - somehow - behind festering stupidity among Egyptian officials.

Prothero reviews Conway Morris

Daniel Prothero, author of one of the best yet most neglected book about evolution for the general public, Evolution: What the Fossils Say and Why It Matters, reviews Simon Conway Morris' book, Life’s Solution: Inevitable Humans in a Lonely Universe.

The thesis of the book is both that humans are an inevitable outcome of evolution, and that life is unlikely to exist anywhere else in the universe.

Prothero discovers why.

This change in tone makes one wonder about the underlying motivation of the author. He’s an optimist about the possibility that humans are the inevitable by-product of evolution, but a pessimist that any other planet has humanoids — how can someone take those two mutually contradictory positions? The mystery is answered in the last chapter, when the author reveals that the whole motivation for his position is religious. Early in the book he trashes and dispenses with the fundamentalist Creationists, but by the end his arguments appear equally slanted and biased. His final chapter bashes agnostic materialists like Gould and Dawkins and veers abruptly off into his own philosophical beliefs, musing about why he finds materialism and agnosticism inadequate to provide “meaning” to life.

As Prothero laments, Morris seems to be aiming for the Templeton Price...

I have written about Prothero since I first started blogging. Search for all posts about him here.

Carnival of Evolution #30 has set sail

The thirtieth edition is hosted by Bob O'Hara on This Scientific Life. Enjoy! And spread the word.

Here's my favorite post this time: Mapping fitness: landscapes, topographic maps, and Seattle by Steve Matheson at Panda's Thumb. Particularly because of the discussion, where Joe Felsenstein himself enters the discussion in the comments, as does Arlin Stoltzfus, and the whole thing is quite a good read.

Ark Park or the P'Ark?

Feast your eyes on this beauty!


Arc Encounter

They are actually going to build the arc. Right next to the Creation Museum in Kentucky, of course.

An office mate of mine wants it to be called the Ark Park. I think The P'Ark is much better. What do you think?

Now point and laugh, and wait for the flood. Except, if they build it, and I hope they won't, they might likely attract lots of people to the P'Ark, and make a ton of money and misinform a bunch of people. Shame.

Also, as PZ points out, I am very upset that they will employ hundreds of people to build it, while for "the real" arc, only eight people were involved. If NOah had divine help, why can't Ken Ham?

Can science tell us right from wrong?

That is the question* posed at this ASU Origins debate that I found my way to via Rationally Speaking I was referred to this debate in which one Patricia Smith Churchland asks which higher mammal babies died unpleasant deaths at high rates in the time before humans started to destroy everything (some paraphrasing), rhetorically. Suggesting that this was not the case. Hmm, I think, what an odd statement, because I imagine that even when humans weren't destroying gorilla habitat, lots of other dangers lurked everywhere and the young ones paid the price.



But then I think I better look her up before I dismiss her remark as a silly ignorant one, because just maybe she has reasons to believe that higher mammals didn't lose their young children much before humans made them. And then I have another experience that I have had several times before, because I see that she is a philosopher, and I immediately realize that what she says is based on no evidence whatsoever. She's doing research in "the interface between neuroscience and philosophy." In other words, no expertise in the field of mammalian suffering™.

However, I find her comment on Hume's is-ought fallacy later (at 8:49 in part 2) very, very true, that all right, no deduction is possible, but other kinds of inferences - the ones we use on a daily basis most of the time.

*And my answer is that all by itself, science cannot tell us right from wrong, but that is not the relevant question. The right question is whether it can inform us on questions of right and wrong, and that it so very clearly can. We don't like poverty (well, some rich people do like that others are poor, but you know what I mean), and science can inform us how to alleviate it, so there.