The Evolution of Drosophila Non-coding DNA

Peter Andolfatto's recent article on the evolution of non-coding DNA in Drosophila has elicited some comments from the blogosphere. A lot of people are referring to it as an analysis of "junk DNA," which can be traced back to this press release by UCSD and this editor's summary in Nature. I am bothered by the term "junk DNA" even when people put the scare quotes around "junk" implying they don't really mean junk or they are not sure if it really is junk. Let's just call it "non-(protein) coding DNA" and relieve it of all the associations with trash and waste.

I am going to try a new approach to commenting on a research article. I have yet to read the entire paper -- I have skimmed the abstract and looked at some of the figures -- so I am going to comment as I take a closer look at it. From what I understand, Andolfatto has looked at whole genome sequences from closely related Drosophila species and found patterns of sequence divergence and polymorphism in non-coding sequences that are not consistent with the neutral model of molecular evolution. I am hoping he can convince me that these patterns are due to selection on non-coding sequences and not demography or hitchhiking/background-selection due to selection on linked coding sequences.

Previous studies of selection on non-coding sequences has focused on conserved regulatory elements, but this approach does not allow inferences of positive selection on non-coding DNA.

"This finding suggests that taking an approach based on sequence conservation alone may lead to a biased view of regulatory evolution. Functionality of DNA sequences implies that they can be subject to both negative and positive selection. If a significant fraction of divergence between species observed in non-coding DNA is positively selected rather than selectively neutral or constrained, this could lead to underestimates of the functional importance of non-coding DNA and cause researchers to overlook the contribution of arguably the most interesting class of mutations in genome evolution -- those reflecting adaptive differences between populations and species. "

Andolfatto took a different approach toward identifying functional non-coding sequences. He looked at coding and non-coding sequences from twelve D. melanogaster individuals and one D. simulans individual from the X-chromosome. He divided the non-coding sequences into 5 classes: 5' UTRs, 3' UTRs, introns, intergenic sequences within 2kb of a gene, and intergenic sequences more than 4kb from a gene. He then calculated a variety of population genetics statistics based on these sequences to determine if any of the non-coding DNA displays signatures of natural selection. I would expect that the UTRs (sequences that are transcribed, but not translated) are under more functional constraint than the intergenic regions and probably also display more signatures of positive selection. I also would expect that the introns would be constrained and have more evidence of positive selection (due to regulatory elements located within), and that the intergenic sequences located closer to genes are under more selection than intergenic sequences further from genes.

So, what does Andolfatto's data suggest? Surprisinglyy, non-coding DNA is more conserved than silent sites within coding DNA. Silent (or synonymous) sites are nucleotides within coding sequence that can be mutated and not change the amino acid encoded by the codon due to the redundancy of the genetic code. Other research has shown that synonymous sites are under weak selection, but Andolfatto finds that the pattern of polymorphism at non-coding sites resembles that at non-synonymous sites (sites within coding sequences that when mutated lead to a codon encoding a different amino acid) more than synonymous sites. This pretty much rejects the possibility that non-coding sites display patterns of selection because they are linked to coding sequences under selection -- we would expect the same patterns observed at non-coding sites when we look at silent sites because they too would be linked to the selected sequences.

Looking at the relationship between polymorphism and divergence at the synonymous sites, non-synonymous sites, intergenic regions, introns, and UTRs, Andolfatto finds a significant excess of divergence at non-synonymous sites and UTRs. Under a neutral model, we would expect divergence to be a good predictor of the polymorphism at a locus. Too much divergence suggests that positive selection has led to the fixation of mutations in a region. This means that the non-synonymous sites and UTRs are probably under positive selection. Remember, previous studies have been able to identify purifying selection in these types of sequences, but you need the polymorphism data to infer positive selection. By doctoring the data set a bit (eliminating rare variants), Andolfatto also finds evidence for positive selection at the other non-coding sites relative to synonymous sites.

The evidence Andolfatto presents paints a picture of sequence evolution where non-coding sequences are under both selective constraint and driven to fixation by positive selection. This is consistent with regulatory regions playing as important a role in adaptive evolution as protein coding sequences. I guess the evo-devo folks have been on to something all this time, it just took a population geneticist to produce the evidence.

---

Andolfatto, P. 2005. Adaptive evolution of non-coding DNA in Drosophila. Nature. 437: 1149-1152.

PZ Myers Stars in Herzog Film?

Has Dr. Myers's love of all things cephalopod gone too far?



For those unfamiliar, this is Werner Herzog.

Weekly Random Ten (28 October 2005)

Back on Friday Edition

Yes, the random ten is back for a special Friday edition. Of course, next week it may be on Tuesday or Thursday, so stay tuned.

Right now I'm in the middle of writing about some experiments I've done and some that I plan to do. Yes, it's (grant) proposal writing time! I've got a proposal for my thesis committee due on Monday for a meeting the following week. I don't have a problem writing the background and motivations, and the preliminary results and analysis aren't too bad either. Some of my results are in preparation for publication, and other results are getting there; I just need to write a brief summary and include a couple of figures and tables.

It's the data analysis for data I don't even have that really gets to me. I fell like its just a string of conditional statements -- if my data looks like this, it would mean this, and then I would do this. Otherwise, I would do this, and it would mean this. If it looks like this, I'll scratch my head and ask my advisor what I should do next. I didn't actually write that last part . . . the idea did go through my, though. Figuring out how to write about data analyses that I've never done leaves me unsure if any of the proposed data analysis makes sense. Luckily, I can co-opt some of the stuff from this proposal for my real grant proposal that's due in a couple of weeks. Plus, I'm hoping to get some good comments from my committee that may lead to a stronger grant proposal.

The bitching is done for now, so on to the evolgen Weekly Random Ten. Let's see if these tunes can help me get through the proposal writing process (this week, with comments).

1. Less Than Lake - Showbiz? Science? Who Cares? [Sounds like the Kansas Kangaroo Kourt.]
2. 311 - Amber [Like that stuff they found with the dinosaur DNA in Jurassic Park.]
3. Bombshell Rocks - Microphone [Sounds like . . . a Rancid knock off.]
4. Bouncing Souls - The Ballad of Johnny X [Hey, it's my favorite band that can't play their instruments.]
5. Sugar Ray - RPM [That nice Mark McGrath named a song after me.]
6. Tilt - Clothes Horse [It seems likes there's a Tilt song on each random ten.]
7. NOFX - Drugs are Good [Hard to disagree with that.]
8. The Used - Lunacy Fringe [Is that the new name for the religious right?]
9. Me First and the Gimme Gimmes - Country Roads [Greatest. Cover band. Ever.]
10. The Distillers - Idoless [An Aussie band for John Wilkins.]

Redefining Gender Roles

From Dictionary.com's word of the day for today:

virago: an ill-tempered, overbearing woman; also, a woman of great strength and courage.

Talk about conflicting definitions. This really makes you consider how language gives us insights into how we define gender roles.

I think I can use it in a sentence:

Mother nature, a vicious virago, punished us yesterday with an early snow -- man did that suck!

Michael Behe -- Reviewed. Rejected. Expert?

It turns out Michael Behe has been called as an expert witness for the defense (aka, the school board) in the Dover Panda Trial, in case you didn't hear. He's gotten some shit for his claim that Darwin's Black Box was more critically reviewed than your run-of-the-mill peer-reviewed journal article. I think that it's been hammered home that he's a bold face liar. I want to focus on my responses to some of the goings on during his first day on the stand. Consider the following exchange between the attorney for the school board (Muise) and the ACLU attorney representing the parents (Rothschild.

MR. MUISE: Your Honor, may it please the Court, I tender Dr. Michael Behe as an expert in biochemistry, evolution, intelligent design, creationism, and science education.
MR. ROTHSCHILD: I'm not sure he was ever actually previously proffered as an expert on science education.
THE COURT: All right. Let's handle biochemistry, evolution, intelligent design, and creationism. Any objection there?
MR. ROTHSCHILD: No, Your Honor.

Now, I don't know what makes someone an "expert" in the eyes of the court, but Behe's caricatured view of evolution hardly makes him an expert in the eyes of this biologist. In response to me telling Dr. Behe that the Society for Molecular Biology and Evolution, one of the largest international societies for evolutionary biologists, would be having their annual meeting in his home state, he seemed surprised that such a group existed. I'll let him claim to be an expert in biochemistry, intelligent design, and creationism, but leave the evolutionary biology to the evolutionary biologists.

Behe is also quite proud of all the invitations he has received to speak at colleges and universities. One such invitation came from Will Provine at Cornell. Here is his testimony about this visit as he is examined by Muise.

Behe: In the fall of the year 2002, a man named William Provine, who is a professor of the history of science and also a revolutionary [typographical error -- should read evolutionary] biologist at Cornell University invited me to come and present a lecture to his introductory class on evolutionary biology.
Q. And who is -- is Professor Provine an intelligent design advocate?
Behe: No. Professor Provine is a very, very strong advocate of Darwinian evolution.
Q. He invited you though to come up and give a presentation to his biology class at Cornell University?
Behe: That's right. I gave an entire lecture of 45 to 50 minute lecture, I believe.
Q. Did he explain to you why he wanted you to comeon up?
Behe: Yes.

MR. ROTHSCHILD: Objection, hearsay.
MR. MUISE: Your Honor, he's going to explain why he came up and his understanding as to why he was given the presentation.
MR. ROTHSCHILD: Exactly my objection.
THE COURT: I'll allow it. I'll overrule the objection.

Behe: His stated purpose was that he wanted students in the class to hear an alternative view to Darwinian evolution so that they could better make up their minds which they thought was more accurate.
Q. Apparently, he didn't consider this was going to cause some harm to his students? Behe: No, his opinion --

MR. ROTHSCHILD: Objection.
THE COURT: Sustained.

If you have ever met Will Provine, you know about his antagonistic relationship with religion. He's not a big fan of free will either, but we'll leave that as a topic for another time. What I want to focus on is the meaning of this invitation. Now, you can take my interpretation as speculation, or even ignore it if you like, but here's what I think: Provine was trying to make a fool of Behe. Provine is a confrontational man; he loves to debate, argue, and show someone up . . . especially if that someone is making arguments founded on religious principles. The course Behe was invited to speak in is also a non-majors course.

This course examines evolution in historical and cultural contexts. This course aims to understand the major issues in the history and current status of evolutionary biology and explore the implications of evolution for culture. Issues range from controversies over mechanisms of evolution in natural populations to the conflict between creationists and evolutionists.

Behe's visit seems to fit the general theme of the class, as it focuses on the social as well as scientific implications of evolution. I saw Provine debate Alex Kondrashov over the role of God in human evolution in this very same class. Kondrashov took the position that the human mind/soul could never evolve and showed evidence of a higher power (everything else could be explained by evolution). Sadly, this was seven years ago, and I don't have any notes from the debate, so I can't say much else about it other than Provine loves to attack God and religion.

I can only imagine what lectures Provine gave prior to or following Behe's visit. I'm sure his intent was not simply to allow Behe to present irreducible complexity in a vacuum. There is a no way Provine did not present a sharp critique of Behe's arguments using either the wealth of information available online or coming up with some of his own points. Simply put, Behe should not feel flattered by this invitation -- Provine's sole purpose was to show his students the best Intelligent Design has to offer, and then smack the shit out of it.

Finally, Behe thinks that professional meetings do not give him enough time to present the important ideas behind Intelligent Design.

The third point is that, one has to understand the structure of meetings to see why they may not be the best place to present such ideas. As I mentioned before, large national scientific meetings have many people, but generally most presentations are made as what are called poster presentations, where you get a large poster board, tape up figures and text on it, and go into a large hall with hundreds of other scientists, and display your poster. People wander by and look at it, and can either read it by themselves or continue on or they can stop and talk with you a bit. But it is not a place for a sustained conversation, a sustained discussion about topics such as intelligent design which require a lot of preliminary background, explanation, and so on. Rather, the seminars and discussions that I've just gone through are, in my opinion, much better forums for presenting such material, because generally you can speak continuously for 50 minutes to an hour. There are generally 20 to hundreds of other scientists, active admissions, and so on, who are listening quite closely to the argument you are making and who can respond with discussion and questions and counter arguments of their own. So I view it as a much better forum than a large national meeting.

Behe's argument in less than one minute:

1. "Darwinists" believe all of evolution has occurred by random single nucleotide mutations and natural selection.
2. There are certain biochemical systems that "Darwinists" have yet to explain the evolution of in a step by step process using their random single nucleotide mutations and natural selection.
3. For everything that the "Darwinists" cannot explain in step by step detail, I claim that an Interior Intelligent Designer, who art in heaven, hallowed be thy name . . . um, GodDidIt!

That would fit on a poster in 72 point font with plenty of room for drawings of flagella, blood clotting cascades, or Jesus on a crucifix.

The Human Genome is a Mess

This week's Nature has a News Feature entitled "Human genome: patchwork people" that focuses on the amount of structural polymorphisms (rearrangements, segmental duplications, large deletions) polymorphic in human populations:

"But even as the ink was drying on the complete [human genome] sequence, some researchers were questioning whether there was really such a thing as the definitive edition of the Book of Life. By skim-reading individual genomes, these scientists were finding bizarre and unexpected irregularities. In some people, whole paragraphs of the text were duplicated, whereas in others, large passages were missing, or even printed backwards."

Gee wiz, who would have thought humans would have structural polymorphisms segregating in natural populations!? I mean, it's not like Drosophila geneticists haven't known about these things for seventy years. But golly, we thought these things caused diseases in humans because we're so gosh darn (ok, I've gotta stop using the stupid 1950s exclamations) special:

"These major revisions turned up in all kinds of people, including many who seemed healthy and normal."

Um, that's because of ascertainment bias. You see, when you only screen for big fuck ups in the genome of sick people, you're only gonna find screwed up genomes in, well, sick people. Guess what, we've know for a while that "healthy" folks have "abnormal" genomes.

"The results of six major surveys of consecutive newborns show that 6 out of 1000 (0.6%) carry one or another kind of chromosome anomaly. The breakdown is as follows: 0.22%, sex-chromosomal abnormalities; 0.14%, autosomal trisomies (+D, +E and +G); 0.19%, balanced structural rearrangements and 0.06%, unbalanced structural rearrangements and others. The frequency of "clinically significant" anomalies has been estimated to be about one-half of the total of all chromosomal abnormalities detected in newborns" (Sankaranarayanan 1979).

In case the jargon was too much, about half of the "anomalies" caused "clinically significant" problems -- that means half of them did not. Many of the abnormalities described resulted in aneuploid individuals (those with an extra copy or missing a single copy of a single chromosome, ie, monosomic or trisomic), and these are probably not heritable. Many of them, however, had inversions or translocations, which are heritable and can increase in frequency in a population due to drift or selection.

We've known about the Drosophila inversion polymorphisms for so long because of polytene chromosomes. We can view the chromosomes by extracting the salivary glands out of larval flies where a single cell has multiple copies of each chromosome stacked on top of each other. In individuals heterozygous for large deletions or inversions, these appear as loops in the polytene chromosomes.





We cannot do this in humans, but now that we have whole genome sequences, there are neat bioinformatic ways to detect large scale chromosomal rearrangements. For instance, some parts of the genome seem to get sequenced twice as often in whole genome sequencing projects -- this is indicative of recent large scale duplications. We can also use single nucleotide polymorphism (SNP) data to detect regions of the genome with abnormal levels of polymorphisms, suggesting some sort of large scale rearrangement.

"Genome researchers now have a catch-all phrase for the vast array of rearrangements -- including copy-number polymorphisms, inversions, deletions and duplications -- that occur normally in the human genome. They call it structural variation, and have described at least 800 individual variants that, in total, account for about 3.5% of the human genome
. . .
"What's more, statistical analyses show that regions of structural variation contain genes that are still evolving in humans. If these genes are important enough for evolution to be changing them, they must affect us in some way, for better or worse."

It's good to see that mammalogists are beginning to examine the importance of these rearrangements outside of their detrimental qualities.

---

Check, E. 2005. Human genome: patchwork people. Nature. 437: 1084-1086.

Sankaranarayanan, K. 1979. The role of non-disjunction in aneuploidy in man an overview. Mut. Res. 61: 1-28.

Tangled Bank #39

Tangled Bank #39 has been posted at The Questionable Authority. Go read about some science.

Weekly Random Ten (19 October 2005)

It's Not Just for Fridays Anymore Edition

Why limit the Random Ten meme to only Fridays? Ok, so the meme is really old, and I rarely see anyone do it anymore, but I'm gonna try to turn it on its head. Once a week -- maybe on a Friday, but maybe on a Tuesday, a Wednesday, or, gasp, even a Sunday -- I'll post a Random Ten. This week's theme: reading a new a comic strip.

I was recently directed to Minimum Security, a poorly drawn comic with a political slant. When I went to check it out, the first comic on the page was this one:



Could it be an omen? Is some higher power telling me to bookmark this page and check back regularly? They do seem to make fun of the same people I can't stand: religious zealots who want to destroy science with their dogma. But then I remembered, I don't believe in fate, karma, or any of that super-natural crap.

Enough with the intro, here's this week's Weekly Random Ten:

1. Union 13 - The Future & The Past
2. Unwritten Law - Teenage Suicide
3. Living End - Hold Up
4. R.E.M. - Orange Crush
5. The Von Bondies - Right of Way
6. The White Stripes - Blue Orchid
7. America - A Horse With No Name
8. U.S. Bombs - Bubble Gum
9. The Kinks - A Well Respected Man
10. Ben Folds Five - Jackson Cannery

Can you marry your half-sister's daughter?

Gary Trudeau poses an interesting question:





Let's lend Zipper and Jeff a hand. Here is a pedigree of the family with Jeff, Alex (Jeff's half-niece), J.J. (Jeff's half-sister and Alex's mom), and Joanie (Jeff and J.J.'s mom) labeled. Jeff and Alex are the filled in symbols. Circles indicate females and squares indicate males. Horizontal lines are matings and the vertical lines lead downward toward the progeny of that mating.



We will define the inbreeding coefficient (f) as the probability that both alleles in a single individual are identical by descent (IBD). IBD simply means that both alleles came from the same allele in one of the ancestors -- in this case, Joanie. We are trying to figure out what is the probability that Jeff and Alex's hypothetical child would get the same allele from both of his/her parents. To do this, we will redraw the pedigree so that we only focus on the individuals in question. Each passing of gametes (birth) is represented by an arrow. Only one of the two parents is shown for each mating. Jeff and Alex's hypothetical child is represented by a diamond.



Joanie has two alleles for the gene in question -- let's call it the "A" gene -- A₁ and A₂. She could have passed either allele on to either of her children, J.J. and Alex Jeff, with equal probability, 0.5. In order for the hypothetical child to get two copies of the same allele (IBD) both Jeff and Alex would have to carry the same allele and they would both need to pass it on to the child. Here are the important probabilities:

1. The probability Jeff gets the A₁ allele from Joanie is 0.5. The probability he passes on the A₁ allele to his child assuming he has the allele is 0.5. The probability he passes on the A₁ allele to his child is the product of these two probabilities: 0.25.
2. The probability Alex gets the A₁ allele from Joanie is the probability J.J. gets the allele from Joanie times the probability J.J. passes it along to Alex. The product of those two events (0.5 x 0.5) is 0.25. The probability Alex passes on the A₁ allele to her child assuming she gets the allele from Joanie is 0.5. Therefore, the probability Alex passes along the A₁ allele to her child is the probability she gets it times the probability she passes it along, or 0.125 (0.25 x 0.5).
3. Now that we have the probability Jeff passes the A₁ allele to his child (0.25) and the probability Alex passes the allele to her child (0.125) we can calculate the probability they both pass the allele on to their hypothetical child if they were to mate. This just the product of the previous two probabilities (0.25 x 0.125): 0.03125, or 1/32.

Up to this point, we have only dealt with the A₁ allele. Jeff and Alex's hypothetical child could also receive the A₂ allele from both parents. Repeating the steps above for the A₂ allele gives the same answer as for the A₁ allele, 1/32. Because the child can either have the genotype A₁A₁ or A₂A₂, the two events are mutually exclusive. This means we can add the probability that the child will be A₁A₁ and the probability the child will be A₂A₂ to get the probability the child will have two alleles that are IBD for a single gene. This gives us a final answer of 1/16.

For any given gene, Jeff and Alex's child has a 6.25% chance (1/16) of being IBD. For most genes this should not be a problem, but if the child ended up being homozygous for a recessive deleterious allele, this could be catastrophic. As the probability of being IBD at a given locus increases, so does the probability of having two copies of a recessive deleterious allele. As a point of comparison, the probability of being IBD for a child from a mating between first cousins is 1/32 1/16. Matings between cousins is generally frowned upon because of the risks associated with heritable diseases. Jeff and Alex's child would have twice the same risk of a heritable disease due to recessive deleterious alleles than as a child from a mating between first cousins.

In conclusion, Jeff can have his half-niece Alex stay with him, but only Zipper is allowed to fool around with her.

---

Hedrick, PW. 1999. Genetics of Populations. Jones and Bartlett Publishers, Sudbury, MA, USA.

Friday Random Ten (14 October 2005)

Back by Popular Demand Edition

Ok, maybe there was no demand, and maybe I'm not all that popular, but my entry on separation of church and state was linked to by Deadspin. In case you don't know, Deadspin is the single greatest sports news site that doesn't deal with actual sports news (this is another in a line of entries in which I plug irrelevant websites). For instance, check out their coverage of Manny Ramirez hanging out with some girls. Or look at what Bronson Arroyo was up to in a Northeastern dorm. They seem to have a lot of junk on Boston Red Sox players, but they don't call them the "idiots" for nothing. If you were a professional athlete, you'd be doing the same thing. If I was Kyle Orton, however, I would not be doing this.

An while I'm on the topic of sports, it turns out my university's women's basketball coach is a homophobe, and our beloved football coach has no problem with it. I wonder if the gay community will have a rooting interest for the maize and blue this weekend?

Before I forget that this is an evolution and genetics blog and not a site for sports gossip, here's this week's evolgen Friday Random Ten. I promise, no umpiring errors here.

1. Screeching Weasel - Cool Kids
2. Satanic Surfers - Killing Me
3. Dishwalla - Counting Blue Cars
4. Rocket From the Crypt - Heart of a Rat
5. Goldfinger - If Only
6. My Chemical Romance - The Ghost of You
7. Goldfinger - My Head
8. Dropkick Murphys - Noble
9. Tilt - Libel
10. Pietasters - Time Won't Let Me

File this under . . .

. . . a victory for the separation of church and state:

EAST BRUNSWICK, N.J. -- A veteran central New Jersey high school football coach has resigned after being told by school officials he could no longer lead his team in pregame prayer.

He's not being punished for being religious; he simple cannot, as a government employee encourage, discourage, or endorse any religion or religion in general. This sums it up perfectly:

A spokeswoman for the district, Trish LaDuca, said students have the right to pray on school property during school events, but the prayer must be initiated by the students; otherwise it violates the law.

"A representative of the school district cannot constitutionally initiate prayer, encourage it or lead it," LaDuca told the Home News Tribune of East Brunswick. Representatives of the school cannot participate in the student-initiated prayer."

There's nothing illegal about praying in school (or anywhere you would like for that matter). The government cannot stop you from practicing your religion. You simply cannot encourage others to do it if you're on the clock with the government. What's so hard to understand about that?

Shakespeare out of our schools!

If you don't read Toothpaste for Dinner, you really should. It's hit or miss, but when it hits, it, well, hits. This isn't one of the hits, but it's relevant given the Darwin out of our schools movement and the recently passed Banned Books Week.



I'll bite my tongue at that. I remember my first ever exposure to Shakespeare in my 9th grade English class. We read Romeo and Juliet (how clich�!), and the teacher made it a point to describe the humor -- even the dirty stuff. Granted, the low brow stuff about swords as phalluses is fairly transparent, but the entire first half is loaded with naughty jokes. It really made it enjoyable to figure out what the characters were saying, making it more than just some classic piece of literature that we had to read. I think Baz Luhrmann was trying to get at that with his version, but it all got lost in the image of a post-contemporary world he was so obsessed about creating.

Can You Find the Typo?

Manyuan Long is one of the leaders in the field of gene duplication. His work on retroposed genes (genes that are transcribed into RNA, reverse transcribed back to DNA, and then inserted into the genome) has yielded insights into the origins of new genes and differences in selective pressures between genes on X-chromosomes compared to autosomes. That said, I just realized that he wrote the following in the abstract of one of his papers:

We focused on the origin of new genes by exon shuffling and retroposition. We will first summarize our experimental work, which revealed four new genes in Drosophila, plants, and humans. These genes are 10⁶ to 10⁸ million years old. The recency of these genes allows us to directly examine the origin and evolution of genes in detail.

Did you notice it? I'll admit, I didn't pick it up until just now -- easily the tenth time I've read the abstract. Look at the age of the genes . . . yes, Dr. Long claims they are 1 trillion to 100 trillion years old. I'd hardly call those recently duplicated genes. In fact, they're older the universe itself (let alone the Earth). I think he meant to say "These genes are 10⁶ to 10⁸ years old," but I need to go through the paper to figure it out. This is the kind of error you would expect to be corrected in peer-review. And, no, Genetica has not issued a correction, or they if they did, it's not posted along with the article.

The Dinosaurs Do Design

Dinosaur Comics has tackled intelligent design:



Evolution is not entirely random -- mutations are random, but natural selection is a deterministic process. Read the rest; there are no great insights, but check out what God has to say about the whole issue.

Note to Molecular Biologists: Quit Misusing "Homology"

Homology: Similarity between species [or DNA sequences] that results from inheritance of traits from a common ancestor (Freeman and Herron 1998, Evolutionary Analysis).

Similarity: The quality or condition of being similar; resemblance. See Synonyms at likeness (The American Heritage Dictionary of the English Language, Fourth Edition).

I've been reading a lot of papers on the molecular biology and genetics of recombination and chromosomal aberrations. For those who aren't familiar with the literature, the mechanisms behind recombination and genome rearrangements (such as inversions, chromosomal translocations, and segmental deletions) are quite similar. They both begin with a double strand break (DSB) and subsequent invasion of a highly similar sequence (usually from the homologous chromosome) in order to repair that break. If the repair comes via a homologous chromosome, we get either gene conversion or a crossing over event. If, however, a non-allelic region (i.e., a similar sequence from a non-homologous region) invades, we can get a chromosomal aberration that may have biological consequences such as speciation or disease.

An overview of meiotic recombination between two homologous chromosomes, based on the DSB repair model, showing intermediates and the proteins implicated in their formation by genetic and/or molecular criteria. The points at which several proteins act is still under investigation, and some may be required at several steps. Proteins that function in both mitotic and meiotic HR are indicated in bold; all others are unique to meiosis. A DSB is introduced in a DNA duplex by the Spo11 nuclease, likely acting in conjunction with several other proteins that are known to be required for DSB induction. The 5' ends of the break undergo 5' to 3' resection to yield 3'-OH single-stranded tails. 3) One of these single-stranded tails invades a homologous duplex, displacing a D-loop. 4) Several steps resulting in the formation of a bimolecular intermediate with double Holliday junctions follow. At this point, correction of mismatches in heteroduplex DNA can result in gene conversion. 5) Resolution of the intermediate to yield a product with a parental configuration of flanking sequences (non-crossover). 6) Resolution to yield a crossover product. (http://www.infobiogen.fr/services/chromcancer/Deep/DoubleStrandBreaksID20008.html)

The molecular biologists who write articles about recombination and DSB repair usually refer to a homologous sequence being used as the template. This is usually the case, as the allele from the homologous chromosome is most common site of genetic exchange. The problem arises when they refer to degrees of homology, distinguishing between sequences of "high homology" or "very little homology" in different repair pathways. To an evolutionary biologist, this sounds like nails on a chalkboard. Homology refers to common ancestry -- two sequences are either homologous (they share a common ancestor) or they are not. There is no in between. It's kind of like being pregnant: you either are or you are not, and you cannot be "a little bit pregnant."

What these diction-deficient molecular biologists mean when they say "homology" is "sequence similarity identity." Similarity Identity can be measured as a proportion or percent and sequences can be highly similar (95% of the same nucleotides) or highly divergent with low similarity identity. This scale of similarity identity ranges from zero percent to 100 percent, although determining similarity identity below 25 percent is impossible due to difficulties in alignment. Even though homology is a yes or no issue, we could think of a case where we have a probability of homology. This would not refer to the amount of sequence similarity identity between sequences, but rather the probability that the sequences are homologous. There would be a correct answer (either yes or no), but due to uncertainties in our ability to determine homology, we would be forced to say we are 80% sure that these sequences are homologous. I'm not sure if anyone does this.

Name That Tune

I know I promised to write about William Harris's talk a couple of weeks ago, and I am working on it -- I got about halfway through and could not muster another thought about creationism. Once I get motivated again, I'll try to dig through the waste and emptiness and finish it up. I hope to have my comments up within the next week or so.

In the meantime, here's a little game to keep you entertained. Let's play a little "Name That Tune"! This one is in the category of "The Conservative Nature of Natural Selection". In how many sentences can you name that tune (author and/or publication):

Sentence #1:

"Natural selection has been extremely effective in policing allelic mutations which arise in already existing gene loci."

Did anyone get it? It doesn't sound like a very controversial statement about what we refer to as purifying selection. Let�s move on to sentence #2:

"Because of natural selection, organisms have been able to adapt to changing environments, and by adaptive radiation many new species were created from a common ancestral form."

Well, it's definitely not a Young Earth Creationist (YEC); YECs don't believe in adaptive radiation. Some Intelligent Designers (IDers) also don't believe in adaptive radiation, but some do. What does sentence #3 hold for us:

"Yet, being an effective policeman, natural selection is extremely conservative by nature."

Oooh, anyone see where this is going? For more sacrilege against the god of natural selection, see sentence #4:

"Had evolution been entirely dependent on natural selection, from a bacterium only numerous forms of bacteria would have emerged."

Natural selection can't account for all of evolution!? All we would have is bacteria!? And "forms" sounds a lot like "kinds". What blasphemy! Ok, maybe it gets better in sentence #5:

"The creation of metazoans, vertebrates and finally mammals from unicellular organisms would have been quite impossible, for such big leaps in evolution required the creation of new gene loci with previous nonexistent functions."

Evolution would have been impossible . . . if it wasn't for this type of event that the author hints at. Some of my readers may see where this is going. I'll give you a clue: we're not talking about a mystical force creating new genes or biochemical pathways. For those of you who need one more line, here is sentence #6:

"Only the cistron which became redundant was able to escape from the relentless pressure of natural selection, and by escaping, it accumulated formerly forbidden mutations to emerge as a new gene locus."

Give up? No, it's not from some creationist tripe. This is actually from the Preface of a well respected book within evolutionary genetics: Susumu Ohno's Evolution by Gene Duplication published in 1970. Yes, even thirty five years ago evolutionary biologists did not need intelligent designers to tell them that natural selection is not the be all, end all of evolutionary forces. We've known it all along, and without gene duplication (via retrotransposition, segmental duplication, and whole genome duplication) evolution would have ceased with the simplest of all prokaryotes.

You see, it's easy to attack a caricature of evolutionary theory consisting of only random mutation and natural selection, but that's just a straw man. Understanding evolution to any extent requires one to examine more than just the pop culture concept of Darwin. Natural selection on allelic mutations cannot explain much beyond within population variation and speciation; to truly appreciate the amazing diversity of life on earth (and some within population variation and speciation) we must invoke genome rearrangements, neutral processes, and many other evolutionary forces . . . or we could just say "Goddidit!"

Lastly, it really bothers me that people justify the ID movement by arguing that it makes biologists consider other things besides natural selection when it really just wastes our time with silly arguments. You can make a pretty good career out of contributing to the knowledge of a field, but to go down as a legend you must lead research in a new direction. The fathers of evolutionary genetics (Dobzhansky, Wright, Fisher, Haldane, et al) did just that. So did Ohta Kimura with his neutral theory. We don't need anyone telling us to do good research and come up with new ideas. Now, you can argue that ID is just the newest in a long line of novel evolutionary concepts. Of course, you would be wrong if you did. See, what differentiates Behe, Dembski, and Wells from the real scientists is that the latter actually understood the field they were revolutionizing. Attacking the god of natural selection is a pitiful battle because no real evolutionary biologist worships at that altar.

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Ohno, S. Evolution by Gene Duplication. Springer-Verlag, New York, NY.