Stop Using the Term "Noncoding DNA:" It Doesn't Mean What You Think It Means

Axel Visel is a member of the ENCODE Consortium. He is a Staff Scientist at the Lawrence Berkeley National Laboratory in Berkeley, California (USA). Axel Visel is responsible, in part, for the publicity fiasco of September 2012 where the entire ENCODE Consortium gave the impression that most of our genome is functional.

He is also the senior author on a paper I blogged about last week—the one where some journalists made a big deal about junk DNA when there was nothing in the paper about junk DNA [How to Turn a Simple Paper into a Scientific Breakthrough: Mention Junk DNA].

Dan Graur contacted him by email to see if he had any comment about this misrepresentation of his published work and he defended the journalist. Here's the email response from Axel Visel to Dan Gaur.

The Carnival of Evolution #65: Horror Host Edition

The latest issue of Carnival of Evolution is hosted by PZ Myers, a developmental biologist with an interest in evolution (among other things). He's a professor at the University of Minnesota in Morris. PZ blogs at Pharyngula. Perhaps you've heard of it?

Read: The Carnival of Evolution #65: Horror Host Edition.

I prepared for the Carnival of Evolution late at night over the last several days, bracketing the Halloween holiday, and coupled them with my traditional custom of watching horror movies. It wasn’t a good match. The evolutionary stories were far more frightening!

There are several dozen contributions and some of them are very scary.

If you want to host a Carnival of Evolution please contact Bjørn Østman. Bjørn is always looking for someone to host the Carnival of Evolution. He would prefer someone who has not hosted before but repeat hosts are more than welcome right now! Bjørn is threatening to name YOU as host even if you don't volunteer! Contact him at the Carnival of Evolution blog. You can send articles directly to him or you can submit your articles at Carnival of Evolution although you now have to register to post a submission. Please alert Bjørn or the upcoming host if you see an article that should be included in next month's. You don't have to be the author to nominate a post.

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How Many Different Cell Types in an Adult Human?

We're having a little discussion about complexity in the comments from my post of last Friday [Vertebrate Complexity Is Explained by the Evolution of Long-Range Interactions that Regulate Transcription?]. I pointed out that many scientists just can't come to grips with the idea that humans aren't much more complicated than other animals. We are not special. I call this The Deflated Ego Problem.

One of the minor arguments in favor of human exceptionalism is the idea that we (mammals?) have more cell types that other species. Therefore, we are more complex. The number that's often bandied about is 210 cell types. PZ Myers debunks this myth (once again) in Methinks it is like a fox terrier". I love it when people like PZ make oblique references to Stephen Jay Gould as he does in the title. If you don't know what this has to do with fox terriers then you're in for a double treat.

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Vertebrate Complexity Is Explained by the Evolution of Long-Range Interactions that Regulate Transcription?

The Deflated Ego Problem is a very serious problem in molecular biology. It refers to the fact that many molecular biologists were puzzled and upset to learn that humans have about the same number of genes as all other multicellular eukaryotes. The "problem" is often introduced by stating that the experts working on the human genome project expected at least 100,000 genes but were "shocked' when the first draft of the human genome showed only 30,000 genes (now down to about 25,000). This story is a myth as I document in: Facts and Myths Concerning the Historical Estimates of the Number of Genes in the Human Genome. Truth is, most knowledgeable experts expected that humans would have about the same number of genes as other animals. They realized that the differences between fruit flies and humans, for example, didn't depend on a host of new human genes but on the timing and expression of a mostly common set of genes.

This isn't good enough for many human chauvinists. They are still looking for something special that sets human apart from all other animals. I listed seven possibilities in my post on the deflated ego problem:

A "Perfect Painting" Proves that Beneficial Mutations Are Impossible and Neutral Mutations Are Impossible

There are times when the stupidity of creationists just makes you gasp. This is one of those times. The creationist is Denyse O'Leary, who holds some kind of record for stupidity.

In this case she can be partially excused since she seems to be quoting someone named Laszlo Bencze. You can read the whole thing at: Is there no such thing as a neutral mutation? Art explains why there probably isn’t.

Denyse quotes Laszlo Bencze (I think) talking about a painting by French artist Jean-Auguste-Dominique Ingres (1780-1867).

Here is a famous and gorgeous painting by Ingres which I just saw in person at the Frick Museum in New York.

Let’s imagine we can improve it by adding a dot of paint 1mm in diameter to it. In evolutionary terms we will give it a “point mutation,” the smallest possible change. If we add this dot randomly, the odds are pretty high it will damage the painting by creating an obvious, intrusive speck. So let’s give evolution every advantage. Let’s make the process far more likely to succeed by having the great contemporary painter, David Hockney, add the speck wherever he thinks it will “do the most good.”

Now I happen to know that Hockney is a great admirer of Ingres and would be shocked and dismayed at any such request. But if a cruel tyrant under pain of death forced him to do it, Hockney would understand that there is no place he could possibly place a dot of paint that would improve the painting. Like a living thing, the painting is so well crafted that anything he might add to it could only be neutral at best. So Hockney would strive to place the most neutral dot he could by choosing a pigment that matched some dark portion of the painting and hope to hide his speck there.

But would such a speck be truly neutral? No matter how well it matched the color, wouldn’t it be visible as a raised dot under the right lighting conditions? And wouldn’t that actually damage the painting even if ever so slightly? And this is precisely Sanford’s point. In the world of biology it is impossible to create a neutral mutation. The change may be extremely slight, even invisible, yet always a degradation no matter how small.

When you think about it, it's really very sad this this is the best the Intelligent Design Creationists can offer. They are so ignorant that you can almost feel sorry for them.

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Time to Re-Write the Textbooks! Nature Publishes a New Version of the Citric Acid Cycle

I was looking through my copy of Nature the other day trying to take seriously all the special reviews on "Transcription and Epigenetics." One article caught my eye ...

Gut, P. and Verdin, E. (2013) The nexus of chromatin regulation and intermediary metabolism. Nature 502:489-498. [doi: 10.1038/nature12752]

Living organisms and individual cells continuously adapt to changes in their environment. Those changes are particularly sensitive to fluctuations in the availability of energy substrates. The cellular transcriptional machinery and its chromatin-associated proteins integrate environmental inputs to mediate homeostatic responses through gene regulation. Numerous connections between products of intermediary metabolism and chromatin proteins have recently been identified. Chromatin modifications that occur in response to metabolic signals are dynamic or stable and might even be inherited transgenerationally. These emerging concepts have biological relevance to tissue homeostasis, disease and ageing.

The authors argue that, among other things, methylation of histones is regulated by changes in the concentrations of some citric acid cycle metabolites. I find it difficult to imagine that the concentrations of the citric acid cycle intermediates could change significantly enough to act as allosteric effectors but that's not what grabbed my attention.

It's the figure showing the citric acid cycle (TCA cycle) that shocked me.

Textbooks show that the products of the citric acid cycle are ...

That's three NADH, one QH₂, and one GTP (or ATP) for a total of ten ATP equivalents. The new version, published last week in the most prestigious science journal in the world, shows that there are six NADH produced per cycle for a total of 15 ATP equivalents. It must be correct because this is a paper about intermediary metabolism and it was reviewed by experts in the field. Unfortunately, the authors don't give a reference to this new information. I assume that it's common knowledge among the top metabolism researchers so they didn't bother citing the papers.

Can anyone out there direct me to the revolutionary papers that I missed?

P.S. I'm not even going to mention that FADH₂ is NOT a product of enzyme-catalyzed β-oxidation.

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I Just Signed Up for an Evolution MOOC!

I'm not a big fan of MOOCs but I just couldn't resist a course called "Evolution: A Course for Educators". The instructors are two Ph.D. employees from the American Museum of Natural History in New York (USA). As you probably know, the American Museum of Natural History is very proud of its tradition in education. Here's what they say on their website.

The American Museum of Natural History is one of the world’s preeminent scientific, educational and cultural institutions. Since its founding in 1869, the Museum has advanced its global mission to discover, interpret, and disseminate information about human cultures, the natural world, and the universe through a wide-ranging program of scientific research, education, and exhibition.

This is a course for educators and that's right up my alley. You may want to sign up as well. Here's the description and the video.

How are all of the species living on Earth today related? How does understanding evolutionary science contribute to our well-being? In this course, participants will learn about evolutionary relationships, population genetics, and natural and artificial selection. Participants will explore evolutionary science and learn how to integrate it into their classrooms.

....

The AMNH course Evolution: A Course for Educators provides an overview of biological evolution for educators. Informed by the recently released Next Generation Science Standards, the course explores the history of evolutionary theory and the evidence that supports it. We will learn about patterns of human evolution and societal implications of modern evolutionary biology, and how scientists determine relatedness among living and extinct organisms. Course participants will bring their understanding of course themes - along with content resources, discussion questions, and assignments - into their own teaching.

It's a bit disturbing that the Next Generation Science Standards don't mention random genetic drift, Neutral Theory, speciation, or population genetics [Natural Selection and Evolution] but the course promises to cover population genetics and I assume that it will also cover all mechanisms of evolution since it's being taught by an evolutionary biologist (Joel Cracraft).

The purpose of the course is to train the next generation of high school (and university) teachers. One of the instructors, David Randle, is an expect on education. We all know that teachers need to be updated on modern evolutionary theory.

It starts next Monday. I'll let you know how I'm doing when I write the first test.

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The Khan Academy and AAMC Teach Evolution in Preparation for the MCAT

Ross Firestone is a 2nd year MD/PhD student at the Albert Einstein College of Medicine. He is one of the winners of the MCAT Video Competition. Apparently the Khan Academy and the Association of American Medical Colleges were impressed with his presentations on evolution. You can see all six videos at Evolution and population dynamics.

I'm posting the first one on Evolution and Natural Selection. It's all about natural selection but it's a very strange kind of natural selection. The organisms are parthenogenic and each individual is genetically programed to have a certain probability of reproducing. One type has a 50% probability of reproducing and another type has only a 25% probability of reproducing. These probabilities seem to be independent of any competition between them. Each successful individual produces four offspring. After some time the number of one type remains constant (25% probability) but the number of the other type (50% probability) doubles with each generation. This is natural selection according to Ross Firestone.

"Naturally," I was disappointed that natural selection was the only mechanism mentioned. There's nothing about random genetic drift in this video and nothing about the stochastic nature of natural selection. But my face lit up when I saw that there was another video on "Alternative Selection: Learn about driving forces of evolution other than natural selection." This could almost make up for screwing up the description of natural selection.

Alas, the second video is even worse. The "alternatives" are group selection and artificial selection. It gets even more worse. The example of group selection is the grandmother hypothesis. According to Ross Firestone, the fact that grandmothers help their grandchildren survive is group selection.

The video on "Bottlenecks and the environment" is also quite interesting. I didn't know that that the peppered moth story is an example of a bottleneck. Did you?


I think these videos are horrible—so horrible, in fact, that the Khan Academy should take them down. What do you think?

Are you wondering why a 2nd year med student feels so confident that he knows enough about evolution to teach it to pre-med students? Me too.

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The Khan Academy and AAMC Teach the Central Dogma of Molecular Biology in Preparation for the MCAT

Here's a presentation by Tracy Kovach, a 3rd year medical student at the University of Virginia School of Medicine. Sandwalk readers will be familiar with my view of Basic Concepts: The Central Dogma of Molecular Biology and the widespread misunderstanding of Crick's original idea. It won't be a surprise to learn that a 3rd year medical student is repeating the old DNA to RNA to protein mantra.

I suppose that's excusable, especially since that's what is likely to be tested on the MCAT. I wonder if students who take my course, or similar courses that correctly teach the Central Dogma, will be at a disadvantage on the MCAT?

The video is posted on the Khan Academy website at: Central dogma of molecular biology. What I found so astonishing about the video presentation is that Tracy Kovach spends so much time explaining how to remember "transcription" and "translation" and get them in the right order. Recall that this video is for students who are about to graduate from university and apply to medical school. I expect high school students to have mastered the terms "transcription" and "translation." I'm pretty sure that students in my undergraduate class would be insulted if I showed them this video. They would be able to describe the biochemistry of transcription and translation in considerable detail.


There are people who think that the Central Dogma is misunderstood to an even greater extent than I claim. They say that the Central Dogma is widely interpreted to mean that the only role of DNA information is to make RNA which makes protein. In other words, they fear that belief in that version of the Central Dogma rules out any other role for DNA. This is the view of John Mattick. He says that the Central Dogma has been overthrown by the discovery of genes that make functional RNA but not protein.

I wonder if students actually think that this is what the Central Dogma means? Watch the first few minutes of the video and give me your opinion. Is this what she is saying?

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The Khan Academy and the Association of American Medical Colleges (AAMC) Team Up to Teach Evolution and Biochemistry for the New MCAT

Theme

Better BiochemistryStudents have to write an exam called the MCAT in order to get into American Medical Schools (Canadians students also write the MCAT). The exam is created and marked by the Association of American Medical Colleges (AAMC). The format of the exam is changing in 2015 to include more biochemistry and molecular biology. This means that "pre-med" students will likely be taking more biochemistry and molecular biology courses.

Most American schools teach to the MCAT in their biochemistry and molecular biology courses because there are large numbers of wannna-be doctors in their class. The biochemistry lecturers feel that it's their duty to prep the pre-med students to pass the MCAT. This has a devastating effect on American biochemistry courses [Better Biochemistry: Teaching to the MCAT?] [Better Biochemistry: Teaching ATP Hydrolysis for the MCAT]. It is inconsistent with the American Society for Biochemistry and Molecular Biology (ASBM) goals of developing concept-driven courses that focus on fundamental principles [Fundamental Concepts in Biochemistry and Molecular Biology ].

The Khan Academy is taking advantage of the new MCAT in 2015 by posting a series of videos on basic biochemistry and evolution. The content is approved by the AAMC in order to make sure it is suitable for MCAT preparation. Here's what they say on their website [Khan Academy MCAT].

This collection is being developed for the revised MCAT® exam that will first be administered in spring 2015. Videos will be added to the collection through fall 2014. All content in this collection has been created under the direction of the Khan Academy and has been reviewed under the direction of the Association of American Medical Colleges (AAMC). All materials are categorized according to the pre-health competencies tested by the MCAT²⁰¹⁵ exam; however, the content in this collection is not intended to prescribe a program of study for the MCAT²⁰¹⁵ exam. The content is also included in the Pre-health Collection within MedEdPORTAL’s iCollaborative sponsored by the AAMC: www.mededportal.org/pre-health *MCAT® is a program of the AAMC and related trademarks owned by the Association include Medical College Admission Test, MCAT, and MCAT²⁰¹⁵. For more information about the MCAT exam visit : www.aamc.org/mcat2015.

So, how did the Khan Academy prepare the videos? They set up an MCAT Video Competition and picked the best ones. You can read about the winners at MCAT Video Competition Winners. It's an eclectic mix of people but 11 out of 15 winners are medical school students or graduate students. Keep in mind that teaching introductory subjects like evolution and biochemistry is hard and Teachers Have to Know Their Subject.

I'm going to look at the videos on evolution prepared by a second year MD/PhD student at Albert Einstein College of Medicine and videos on biochemistry prepared by a second year MD student at Harvard Medical School and a third year med student at the University of Virginia School of Medicine. Medical students are very bright and very confident of their abilities. We'll see if these students learned enough in their undergraduate courses to be able to create accurate videos that will help university graduates pass the MCAT.

Before looking at some specific examples, let me make a general comment on Khan Academy videos. I've looked at quite a few of them over the years and every single one I've seen is a "kindergarten-level" video. What I mean by that is that the level of the presentation is barely suitable for students beginning high school and in some cases they really are pitched at the level my three-year old granddaughter could understand in a year or two. They certainly aren't up to the level of any university course that I've ever taught.

These MCAT videos are no exception. But they are intended for students who are about to graduate from university. Most of these students will be getting a science degree. The mini courses are intended for students who are about to write the MCAT exam and this should represent the level of knowledge expected of medical students. As a general rule, the students who are preparing for the MCAT have achieved high grades in their biology and chemistry courses and in their biochemistry and molecular biology courses. They wouldn't be considering medical school if they weren't in the top 25% of their class.

Why are the videos pitched at such a low level of education? Is this truly representative of the quality of university education in American universities? Check them out for yourself at: Biomolecules.

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Teachers Have to Know Their Subject

I've said it before and I'll say it again. The top three criteria for good teaching are: (1) accuracy, (2) accuracy, and (3) accuracy. Everything else is in fourth place or lower and that includes style. If what you're teaching is not accurate then nothing else matters.

It is hard to teach an introductory science course. You have to go back to basics and make sure that what you cover all the fundamental principles and concepts and that ain't easy. That's why the best teachers in introductory courses are often senior professors and lecturers with plenty of experience behind them. They have learned what's important and what's not and they can tell the difference between wheat and chaff.

PZ Myers puts it very well in a blog post defending teachers [Teaching is so easy, anyone can do it!].

One of the first things you learn when you start teaching is that you have to know the content inside and out — it’s simply not enough to know the bare minimum that you expect the students to master, because as a teacher, you need to push just a bit farther to get them up there. You need to be able to lead them to knowledge, and you need to be able to point off in the distance to all the cool stuff they can learn if they continue. How can you inspire if you’re not drinking deeply from the Pierian Spring yourself?

Keep this in mind next time we discuss teaching evolution and biochemistry. Teachers have to be experts and it takes a lot of work to make sure you know your content. If what you're teaching is not correct then you are not a good teacher no matter what the student evaluations say. And it's not only a question of accuracy—as PZ points out, you need to be more than a few steps ahead of your students in order to inspire them to do better.

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Submitting to Carnival of Evolution

PZ Myers is hosting the next Carnival of Evolution [Guess who’s hosting the Carnival of Evolution?]. I tried submitting an article but I was unable to read the stupid fuzzy words that you need to type before submitting. Now I can't submit unless I log in. When I do that, my time seems to expire before I can enter the necessary information. Very frustrating.

So, I figured I would just add a comment on PZ's blog. Easier said than done. You have to log in to his blog and none of my usual names and passwords work. I'm beginning to understand why submissions to the Carnival of Evolution are way down.

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Michael Egnor Keeps Digging

When you find yourself in a hole, stop digging.
Will RogersI favor teaching biochemistry from an evolutionary perspective and I was pleased to see that ASBMB considers evolution to be one of the fundamental concepts in biochemistry and molecular biology [ASBMB Core Concepts in Biochemistry and Molecular Biology: Evolution]. (ASBMB screws up their description of evolution but at least their heart's in the right place.)

Unless they understand evolution, students can't really understand why some parts of a protein are the same in all species and other parts are quite variable. They certainly can't understand why you can construct a phylogenetic tree from sequences and why this tree closely resembles those trees made from comparing anatomy/embryology. They won't know why those molecular trees are consistent with a fossil record unless they understand evolution.

Monday's Molecule #221

Last week's molecule was 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU). It is an intermediate in the degradation pathway from uric acid (or urate) to carbon dioxide and ammonia. Uric acid is the main breakdown product in purine catabolism. Humans have lost activity of all of the enzymes of this pathway so they excrete urate. Most other species excrete ammonia, although in other animals some of the terminal enzymes have been lost.

Some textbooks do not show the uric acid degradation pathway since it doesn't occur in humans and those textbooks aren't interested in an evolutionary approach to biochemistry (e.g. Berg, Tymoczko, and Stryer). The other majors textbooks (Voet & Voet, Garrett & Grisham, Nelson & Cox [Lehinger]) all show uric acid converted directly to allantoin via urate oxidase. This reaction was shown to be incorrect about 15 years ago. The actual pathway from uric acid to allantoin involves two intermediates; 5-hydroxyisourate and OHCU.

Image Credit: Moran, L.A., Horton, H.R., Scrimgeour, K.G., and Perry, M.D. (2012) Principles of Biochemistry 5th ed., Pearson Education Inc. page 568 [Pearson: Principles of Biochemistry 5/E] © 2012 Pearson Education Inc.

The winner, for the second week in a row, is Jean-Marc Neuhaus. [Monday's Molecule #220]. Jean-Marc lives in Switzerland so I've made arrangements to fly over there to visit him and treat him to two fondues at the Pinte de Pierre-à-Bot in Neuchatel. Jean-Marc was kind enough to send me a menu [PDF]. There are about 30 different fondues to choose from. If you would like to join us you can leave a comment on last week's post.

This week's molecule is related to a discussion we are having on the How Do the IDiots Explain the Origin of Life? post. Can you identify this molecule? You have to be very specific.

Email your answer to me at: Monday's Molecule #221. I'll hold off posting your answers for at least 24 hours. The first one with the correct answer wins. I will only post the names of people with mostly correct answers to avoid embarrassment. The winner will be treated to a free lunch.

There could be two winners. If the first correct answer isn't from an undergraduate student then I'll select a second winner from those undergraduates who post the correct answer. You will need to identify yourself as an undergraduate in order to win. (Put "undergraduate" at the bottom of your email message.)

Trace Dominguez of Discovery News Says 98% of Your Genome Is Junk

Theme Genomes & Junk DNAI happened to stumble on this video where Trace Dominguez (@trace501) promotes the idea of junk DNA based on the C-value Paradox—a version of the Onion Test. It's good that he tells the general public about junk DNA but it's bad that he equates "noncoding DNA" with "junk DNA." It's really silly to tell people that the only important part of your genome is the 2% that codes for proteins.

Just so you know, some of the important known functions of "noncoding DNA" are [What's in Your Genome?] ....

1. Genes for functional RNAs like ribosomal RNA, tRNA, and a host of others.
2. Regulatory sequences that control expression of all genes.
3. Part of intron sequences.
4. Origins of replication;specific sites where DNA replication begins.
5. Telomeres.
6. Centromeres.
7. SARS or scaffold attachment regions; sites required to organize chromatin.
8. Functional transposons or "selfish DNA."
9. Functional DNA and RNA viruses.

Scientists believe that about 2% of our genome encodes proteins and about 8% has other functions. It is not true that all noncoding DNA is junk. No knowledgeable scientist ever said that.

I realize that the kind of presentation shown in this video doesn't lend itself to a detailed description of noncoding DNA functions but surely we can do better than this? Why not say that scientists have determined that genes make up about 2% of our genome and about 8% contains information necessary for the proper functioning of genes and chromosomes? The rest, about 90%, is thought to be junk?

98% of your DNA is junk

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