I don't get it.

I suppose that if you do not understand a joke it loses all humor when it is explained to you. That being said, can anyone explain to me what this means?

Does Intelligent Design Leave a Genetic Signature?

I haven't posted anything of substance in a while, and I thought I should explain why -- as if anyone cares. I've been busy putting together presentations for two meetings: the Northeast Ecology and Evolution Conference (NEEC) and the Drosophila Research Conference (Fly Meetings).

I gave a talk at NEEC on patterns of gene duplication in my study species, Drosophila pseudoobscura. Gene duplication provides new genes on which natural selection and other evolutionary forces can act. It is thought to be evolutionarily important as it allows for increased organismal complexity. It's also worth pointing out that Michael Behe conveniently ignores the role of gene duplication in biological systems when he claims that certain mechanisms are "irreducibly complex." I brought this up at a seminar of his that I attended, and he never really got around to addressing it directly.

I also just finished putting together a poster for the Fly Meetings on a specific type of gene duplication. This one gets a bit more technical, and the amount of jargon I begin to spew when discussing it makes it totally un-bloggable. I'd also like to mention that this meeting is in San Diego, which should be a welcome respite from a snowy spring in the northeast.

So, what's with the title of this entry? I spend a lot of time looking at genome sequence data. I'm taking a break from it right now to give my eyes a rest, so I figured I'd post something. I found this title in my unposted blog entries and noticed there was no text. I said to myself, "Let's see what I can write on this," and then went entirely off topic. I'll now try to address the title (briefly).

Evolutionary geneticists have developed a lot of statistical tests for natural selection using DNA sequences. I blogged about one such test before, but it's a bad example and I was extremely critical of it. There are many other tests that have withstood skeptical judgment from the research community and they can be found in numerous publications. I use some of these tests for analyzing my data, and I'm trying to develop one for comparing duplicate genes. Basically, a substantial amount work goes into figuring out how to detect natural selection from genetic data.

I'd assume that if Intelligent Design were a naturally occurring process, it, too, would leave genetic signatures. It's fairly straight forward to perform a simple test for natural selection using DNA data (the hard part comes in determining when the test can be applied, what assumptions are made, and coming up with more complex analyses) because genetic data is less convoluted than phenotypic or behavioral data. Instead of searching for ID in "irreducibly complex" biological systems, why don't IDists mine the many genome sequences freely available for evidence of a designer? I have an idea of what they may find -- or rather NOT find.

That is all for now.

Tangel Bank #24

Tangle Bank #24 is available online. Go out and read about some science.

Politically Incorrect History??

An article in Slate reviews a recent bestselling "history" book: The Politically Incorrect Guide to American History. From what I've read about it, the book appears to be the far right's answer to Howard Zinn's A People's History of the United States. Why am I writing about a history book on an evolutionary genetics blog? Well, the Slate review points out a similarity between this neo-con anti-intellectualism and the anti-evolution movement:

[I]n the Bush years, conservatism has embraced not only the familiar ridicule of the eggheads but a rejection of the very legitimacy of independent, nonpartisan expert authority. The wisdom of legal professionals, such as those in the American Bar Association, is now denied, and, since George Bush took office, no longer used by the White House in evaluating candidates for federal judgeships. Mainstream journalism, such as that in the major newspapers and network news shows, is deemed liberal, slanted, and unreliable. The faith-based belief in creationism, enjoying renewed support of late, is accorded equal (or greater) weight as the scientific theory of evolution.
(The emphasis is my own.)

First of all, I'm proud of the author of the review (David Greenberg, an Assistant Professor in the History Department at Rutgers University) for recognizing that creationism is nothing more than "belief" while evolutionary biology is "theory." It appears we may be getting the message across.

I'd like to avoid political statements at all times on this blog, but I'll break the rules because the author (or his publishers) are attacking academia. The Politically Incorrect Guide's cover states:

Everything (well, almost everything) you know about American history is wrong because most textbooks and popular history books are written by left-wing academic historians who treat their biases as fact.

Now, I always thought that Zinn wrote his book because traditional textbooks often taught history from the perspective of the power elite.

A People's History of the United States is the only volume to tell America's story from the point of view of -- and in the words of -- America's women, factory workers,African Americans, Native Americans, working poor, and immigrant laborers.
-from the back cover of A People's History

If Zinn wrote his book to tell the story of underrepresented groups that textbooks tend to neglect, then I'd have to assume that most history books are not "left-wing academic" propaganda. By claiming the moderate is the far left, the radical right attempts to appear more moderate. Similarly, by falsely legitimizing creationist beliefs and attacking evolutionary theory, creationists are trying to artificially inflate the scientific legitimacy of their ideas. You cannot change what is mainstream by claiming the norm is radical, just like you can't make your ideas scientific by attacking the imperfections in science.

Addendum to "On the fringe"

It just occurred to me that John Davison's qualm with Darwinian theory is like a doppleganger to Ernst Mayr's complaints about "bean bag genetics."

Davison:

[T]he Darwinists refuse to consider that evolution might be subject to laws and precise mathematical relationships such as those that govern virtually every aspect of the inanimate world.

The beanbag genetics that Mayr mocked attempted to do precisely that -- come up with mathematical formulas that govern evolutionary genetics. Of course, Davison is not mocking the noted beanbag geneticists such as Haldane, Wright, or Fisher; he is, in fact, ignorant of their body of work. This puts new meaning to the phrase "argument from ignorance."

On the fringe.

I've recently been introduced to another "anti-darwinist" on the Panda's Thumb, John A. Davison professor of zoology at the University of Vermont. Dr. Davison has an evolutionary manifesto published on his website, in which he claims that natural selection on allelic variation does not result in major evolutionary changes. He also likes to poke fun at mainstream evolutionary biologist by calling us "Darwimps."

In all honesty, I have not read Davison's entire manifesto nor his article on the Prescribed Evolution Hypothesis (PEH). He did not tell me what PEH stands for and where I could find the article, so it took a bit of searching on my part to locate it. I hope to have a post discussing his ideas in more detail in the coming weeks. For now, I'd like to focus on Dr. Davison's misunderstanding of how most biologists understand evolution based on my interactions with him and the parts of his manifesto that I have read.

Perhaps the most compelling feature for the Darwinists resides in their persistent conviction that all of evolution is the result of blind chance. In so doing, the Darwinists refuse to consider that evolution might be subject to laws and precise mathematical relationships such as those that govern virtually every aspect of the inanimate world. (from Davison's manifesto)

Apparently Davison does not realize that Darwinian evolution is a deterministic process (as opposed to stochastic). By definition, deterministic processes do NOT work by chance. The raw material on which natural selection operates (mutations of different sorts) is generated via mutation (a stochastic process). This is a point we should be hammering home as often as possible. Yes, there are stochastic processes involved in the the most widely held scientific view of evolution (mutation, genetic drift, environmental changes), but natural selection is not random. If he does not understand this simple concept (covered in any undergraduate evolution course) how can I take anything in the manifesto seriously.

Davison likes to focus on karyotypic evolution and he believes that genome rearrangements are the things that can cause evolution. I don't dispute his claim that genome rearrangements are important in evolution, but they are just another stochastic event that influence recombination rate (yet another, stochastic process). Recombination rate influences the strength of natural selection (search "recombination" and "selection" in PubMed to see the laundry list of publications), and we're back to the deterministic nature of evolution.

Davison seems to focus on one topic (genome rearrangements) while ignoring all of the other evolutionary forces. Each force is not an isolated mechanism, but rather part of a larger system in which the interaction of natural selection, population size and structure, genetic recombination, environmental changes, learned behaviors, etc. cause evolution. There is a random nature to evolution, but there are also rules that govern how the random events occur (probability distributions) and deterministic processes (natural selection) that depend on those random events.

On the origin of life.

One of the great unsolved mysteries facing modern biology is the origin of life from non-living material, termed abiogenesis (see here and here). While this is not evolution per se, once life has arisen evolution can proceed. A couple of articles appearing in a recent publication of Gene attempt to tackle two important genetic innovations: the origin of RNA and the origin of the genetic code. RNA molecules and the genetic code are necessary parts of the central dogma of molecular biology, and figuring out how they arose will help us get a clearer picture of biological evolution on earth.

On the origin of RNA:
It is thought that life originated in an "RNA world." The RNA molecules may have been stabilized and protected from environmental hazards by affixing themselves to clay substrates. In order to test the plausibility of this hypothesis, Franchi and Gallori compared RNA degradation on a clay substrate versus free RNA. They also performed experiments to determine whether RNA affixed to clay was self-replicable (an important requirement for biological evolution) .

Franchi and Gallori compared the rate of degradation between free RNA chains and clay-bound RNA chains and found that RNA affixed to the clay substrate has a significantly higher half-life when exposed to chemicals capable of breaking up the RNA chain. This suggests that the substrate somehow protects the molecule from environmental hazards, and that a substrate of some sort may have been necessary during the origin of life.

Was this substrate-bound RNA capable of self-replication? The authors show that clay-bound RNA chains are able to attract and bind free nucleotides and form complementary chains. Furthermore, RNA attached to the substrate was reverse transcribed just as efficiently as free floating RNA. (Reverse transcriptase takes an RNA strand and produces a complementary DNA strand.) These two findings show that RNA bound to a clay substrate is self-replicable -- an essential requirement for life to originate and evolve.

On the origin of the genetic code:
It has been hypothesized that life could have originated as many as 10 different times during primitive earth conditions. Determining where life originated could allow researchers to narrow down the list of possible sources of modern life. Di Giulio believes that there should be a signature of the original environment in the genetic code of modern organisms. Previous research lead to the reconstruction of the rRNA of the last universal common ancestor (LUCA) and led to hypotheses regarding where this organism lived based on its nucleotide content.

[A short aside: The genetic code is made up of four different nucleotides: adenine (A), guanine (G), cytosine (C) , and thymine (T). In RNA molecules, thymine is replace by uracil (U). Adenine binds with thymine and guanine binds with cytosine in the DNA double helix, but these bonds are not equal in strength. Guanine and cytosine are held together by three hydrogen bonds, while adenine and thymine are held together by only two. Geneticists use the percent of guanine and cytosine in a DNA sequence (G+C content) to get an idea of how strong a stretch of DNA double helix is held together. High G+C content regions are held together by more hydrogen bonds than low G+C content regions. It is thought that organisms that live in extreme environments have high G+C content to prevent the high temperature from breaking apart the DNA double helix.]

Di Giulio looked at amino acid content in two different Pyrococcus species -- one that lives 0.5 meters below the surface of the ocean and one that thrives around deep sea vents at high pressures (a barophile). He determined which amino acids are preferentially used in each species, and showed that the amino acids in the barophile are encoded by more codons than those in the non-barophile. He postulates that the number of codons that code for an amino acid reflects the frequency or importance of that amino acid in the genome in which the genetic code evolved (the more codons that code for an amino acid, the higher that amino acid's frequency in the progenitor genome). Because environmental pressures influence amino acid content it is believed that convergent evolution should lead to similar amino acid content between extant organisms and the progenitor genome.

He concludes that the genetic code originated in a barophilic organism because the barophilic Pyrococcus species's genome has amino acids that are encoded by more codons than those in the non-barophile. This approach could also be used to compare amino acid content between organisms living in extreme environments to determine what other conditions lead to the origin of life.

A few closing remarks:
In order for biological evolution to proceed, life must be replicable and be acted on by natural selection. How these features arose is one of the great mysteries in biology. RNA (thought to be the first genetic information) seems to persist and be replicated on clay substrates. We still do not know what enzyme acted as the first RNA replicator, and we do not know how primitive genetic information became encapsulated in a membrane.

Once a primitive nucleotide chain could persists and self replicate, it became possible for it to encode information. Modern DNA and RNA encode information regarding amino acid sequences (proteins) and when, where, and how those proteins should be expressed. Natural selection can act on these proteins and lead to evolution of the coding sequence. It appears that this coding sequence first evolved in a high pressure, deep sea environment. It remains to be seen what other environmental forces were necessary for the evolution of the genetic code.

Sequencing the Genome of . . . NYC air?

Craig Venter is at it again! First, he pioneered shotgun sequencing. Then he went and sequenced a bunch of organisms (e.g., humans, Drosophila melanogaster, both the malaria parasite and its mosquito vector). Now he's going around the world on his yacht sequencing DNA from random organisms in the oceans. While he's at it, he's proposing sequencing DNA from organisms in New York City's air (subscription required).

In a pilot project scheduled to be officially announced today, a team from Dr. Venter's nonprofit organization, the J. Craig Venter Institute, is using a filtering device to take air samples from atop the roof of a 40-story office building in the most congested part of Midtown.

...

While much is known about various pollutants, only a tiny percentage - about 1 percent - of the micro-organisms in the air can be identified by traditional methods involving growing cultures. The new process is intended to provide as intimate a picture of the air as the genome mapping provided of the human body.

The genetic information could then be used to create a comprehensive background image of New York's air. In turn, that would make it easier to identify any dangerous new organisms that come from an act of bioterrorism.

I don't have much to say about this. It's just crazy. Not crazy bad. It just makes you wonder what he's gonna sequence next.

Ripping someone a new asshole using only a single genome.

You know what I love about science? Someone makes a crackpot claim, and everyone in the research community is there to jump on it and show how back-ass-wards the proposition is. Take, for example this paper that appeared in Nature last year in which the authors propose a new method for detecting natural selection using only a single genome.

Traditional methods for detecting natural selection using DNA sequence data require at least two sequences to be compared. For example, you may have the sequence of a gene responsible for nerve cell development from a human and the homologous gene from a chimpanzee. You hypothesize that evolution of this gene along the human lineage was responsible for some neurological innovation that lead to a cognitive difference between humans and chimps. In order to test your hypothesis, you must determine if natural selection acted on that gene in the human lineage. You could look for an excess number of amino acid substitutions between the two sequences, which would suggest rapid protein evolution along one of the lineages. This type of selection is known as positive selection. Conversely, a deficiency of amino acid changes would suggest purifying selection (selection for constrained function). Importantly, all accepted methods for detecting natural selection rely on comparing multiple sequences.

The new method introduces a metric known as codon volatility, based on the concept of mutational robustness. The authors propose that a gene under strong purifying selection will be robust to mutations that affect its function, and this robustness should be detectable based on the codons present in the gene. More volatile codons (those that are less robust to amino acid changes) should be common in genes under positive selection, whereas genes under purifying selection should have less volatile codons.

When it was first published last April this article raised some eyebrows in my department as many people were skeptical of the methods. Our doubts were confirmed as critiques came pouring in over the past few months from leading researchers at UC Davis, Cornell, Univ of Chicago, Nottingham, South Carolina, Univ of Houston, and Michigan. These articles were published in Nature, Molecular Biology and Evolution, and Genetics. Among the criticisms of the method are that it:

• Ignores effect of codon bias on volatility.
• Is too sensitive to assumption of mutational process and unable to detect positive selection.
• Only detects usage of a amino acids.
• Makes erroneous assumptions regarding the distribution of synonymous substitutions.
  
• Is not consistent with other, well established, methods for detecting selection.
• And positive selection has no effect on codon volatility in theoretical analyses.

That's what you get when you try to support your claims with hand waving! I'm very surprised that this article made it into Nature as it doesn't even appear to be statistically rigorous enough for Genetics or Mol. Biol. Evol. They authors hold their ground in defense of their article, and only time will tell if their method will fall by the wayside or make it into mainstream molecular evolution research. At least they've got a step up on the IDers who haven't even published anything original.

For some reason, Nature loves publishing flashy, yet crappy, science. My favorite Nature faux pas comes from Dancing Naked in the Mind Field by Kary Mullis (the inventor of PCR). In his book he discusses submitting a letter to Nature about astrophysics as a graduate student. He admits that he knew very little about the subject, but it was published none-the-less. After coming up with PCR, he submitted his paper to Nature thinking that an idea that revolutionary would definitely be accepted -- it was not!

Trackbacks.

After a little bit of tinkering, I have enable trackbacks via HaloScan. This required me to figure out some of the code that blogspot provides. I consider this quite an accomplishment for someone whose only web programming experience consists of some limited exposure to HTML.

I also managed to keep my blogger comments section and only use the HaloScan trackbacks (HaloScan tried giving me a second comments section, but I got rid of it). I'm not sure if I'm supposed to do this, but I didn't want to lose the few comments I had, and I didn't want two different comments sections. Hooray for me.

It's now back to work analyzing data for presentations at the Northeast Ecology and Evolution Conference and the Fly Meetings.

Evolution: Theory or Fact?

Time to nitpick:

The creationist cry, "Evolution is only a theory!" The biologists retort, "Evolution is both a theory and a fact!"

We've heard this point countless times, but I'd like to clarify an issue of hierarchy that is often times neglected. Evolution is a fact. We know that life on earth has changed over time, and that is the essence of the fact of evolution. Evolution is not a theory! There are, however, multiple theories for how life evolved over time.

The accepted mechanisms for how evolution occurs include both deterministic (natural selection) and stochastic processes (random changes such as genetic drift or founder events). Mutation provides the raw material upon which these forces act, but it is a weak evolutionary force on its own. Different evolutionary theories propose how the evolutionary forces interact, but they all assume naturalistic forces are responsible for evolution. There is no one "theory of evolution."

Intelligent design is not a theory. It can be classified as an untested hypothesis, and unless someone starts publishing results, it will remain an untested hypothesis. All of the accepted evolutionary theory has been tested and shown to reasonably explain some aspect of evolution. Intelligent design falls underneath the net of evolution, as it attempts to explain how life on earth has changed over time. This distinguishes it from young earth creationism, which does not acknowledge evolution as a fact. The problem with intelligent design is not that it challenges evolution, but that it is a sub par hypothesis to explain how evolution occurs.