I've been teaching my students about random genetic drift, phylogenetic trees, and the molecular clock. It's hard for undergraduates to understand that trees based on sequences are reflections of the fixation of nearly neutral alleles by random genetic drift. That's because they, like almost everyone else, think of evolution in terms of natural selection and adaptation.
It's even harder to grasp the idea of a molecular clock even though it's been around for fifty years. It was back in the 1960s that scientists like Emanual Margoliash noted that the rate of substitution of amino acids in every lineage was remarkably similar [The Modern Molecular Clock]. We now know that this is because the alleles are fixed by random genetic drift and that the rate of fixation by drift depends only on the mutation rate. It looks like the mutation rate is relatively constant in all lineages (bacteria, protozoa, plants, animals, etc.). This isn't a big shock since the vast majority of mutations are due to errors in DNA replication and the fundamental biochemistry of DNA replication and repair are similar in all species.
There's a big difference between publishing the complete sequence of a genome and having a highly accurate "finished" version that's fully annotated. You may be surprised to learn that there aren't very many high quality genomes of eukaryotes—especially vertebrates.
That's why I was interested in a paper published last April on the zebrafish genome. The authors have produced a high quality reference genome that will serve the scientific community (Howe et al. 2013).
Sequencing and assembly are highly automated and there are several programs that will find genes and other interesting bits of a draft genome. It's a lot more work to finish off the sequence by filling the gaps and it's even more work to annotate and check the sequences. Much of this work is labor intensive and expensive and that's why there are so many unfinished sequences in the literature.
I wasn't surprised to see that the original paper on the annotated zebrafish genome had 171 authors although that did seem a bit excessive. It meant that each author contributed an average of 0.6% to the final result. Some of them must have made a much smaller contribution. I wonder if every author read and approved the paper before publication?
Apparently there weren't enough authors. The January 9, 2014 edition of Nature contains a Corrigendum (correction) to the zebrafish paper. Five other authors were "inadvertantly ommitted" from the list bringing the total to 176 authors. In addition, the names of three other authors were spelled incorrectly in the original publication last April. I don't know why it took eight months before anyone noticed.
That just goes to show you that modern scientists have to deal with problems that us old fogies never encountered. I never had to spent more that a few seconds writing down the names of the authors on any of my papers. Today you need data management software to keep track of your authors.
Howe, K. and 171+5 others (2013 The zebrafish reference genome sequence and its relationship to the human genome. Nature 496:498–503. [doi: 10.1038/nature12111]
Some of us have been trying to educate the IDiots for over twenty years. It can be very, very, frustrating.
The issue of junk DNA is a case in point. We've been trying to explain the facts to people like Casey Luskin. I know he's listening because he comments on Sandwalk from time to time. Surely it can't be that hard? All they have to do is acknowledge that "Darwinians" are opposed to junk DNA because they think that natural selection is very powerful and would have selected against junk DNA. All we're asking is that they refer to "evolutionary biologists" when they talk about junk DNA proponents.
We've also pointed out, ad nauseam, that no knowledgeable scientist ever said that all noncoding DNA was junk. We just want the IDiots to admit that there were some smart scientists who knew about functional noncoding DNA—like the genes for ribosomal RNAs, origins of replication, and centromeres.
There's plenty of evidence that most of the DNA in mammalian genomes is junk [Five Things You Should Know if You Want to Participate in the Junk DNA Debate]. There's also plenty of evidence that as much as 10% of these genomes are functional in some way or another. This is a lot more DNA than the amount in coding regions but that shouldn't surprise anyone since we've known about functional noncoding DNA for half a century.
Lot's of genes specify functional RNA molecules. The best known ones are the genes for ribosomal RNAs, tRNAs, the spliceosomal RNAs, and a variety of other catalytic RNAs. A host of small regulatory RNAs have been characterized in bacteria over the past five decades (Waters and Storz, 2009) and in the past few decades a variety of different types of small RNAs have been identified in eukaryotes (see Sharp, 2009). These include miRNAs, siRNAs, piRNAs, and others (Malone and Hannon, 2009; Carthew and Sontheimer, 2009).
I recently described a really bad paper published in Science by Stergachis et al. (2013). The principle investigator is John Stamatoyannopoulos of ENCODE notoriety [see The "duon" delusion and why transcription factors MUST bind non-functionally to exon sequences].
The group mapped millions of transcription factor binding sites in the human genome and discovered that 1.8% of them were in exons (coding regions). They assumed that these were functional—they play a role in regulating gene expression. Thus the nucleotide binding sites are also codons meaning that the sequence specifies two different kinds of information. The workers named these sequences "duons."
Michael Egnor is a proponent of Intelligent Design Creationism. He's a neurosurgeon practicing on Long Island (New York, USA) and a frequent contributor to creationist blogs. He also likes to comment on Sandwalk from time to time even though it makes him look foolish.
Speaking of looking foolish, he recently got upset about the idea that science and religion are in conflict. He decided to explain how science shows us that God exists. Read it on his blog at: God, in Larry Moran's nose.
This is not comedy or satire. He really believes what he writes.
The proof of God's existence is in Larry Moran's nose, and everywhere, in every atom.
The fact that any subatomic particle moves in a predictable fashion-- let alone in a fashion as mathematically elegant as quantum mechanics-- is straightforward evidence for God's existence. It is, in fact, God's handiwork, manifest everywhere and always.
Richard Lenski's long-term evolution experiment (LTEE) has yielded a number of interesting results over the past two decades. Back in 1988, he set up twelve flasks of E. coli B growing in minimal medium. The cultures were diluted 1/100 every day. There were 6.64 generations per day or almost 2,500 per year. By now, the cultures have evolved for 60,000 generations.
All twelve cultures are under strong selection for rapid growth and all twelve cultures have evolved. One, and only one, of the cultures evolved to utilize citrate as a carbon source (normal E. coli cultures cannot use citrate but it's in the medium as a chelating agent). You can read about the mutations that gave rise to this phenotype in: Lenski's long-term evolution experiment: the evolution of bacteria that can use citrate as a carbon source.
Last week's molecule was arachidonate, one of the key intermediates in the synthesis of complex lipids, especially protaglandins in mammals [Monday's Molecule #227 ]. The winner is Bill Gunn.
This week's molecule (left) is an easy one for all of the undergraduates who are just beginning a new term. This is one of those molecules that everyone should recognize. Just be sure you pay attention to all the groups and the part in red. All you have to do is supply the common name and NOT the IUPAC systematic name that correctly identifies the exact molecule shown in the image. However, if anyone wants to supply the systematic name, feel free to do so.
Email your answer to me at: Monday's Molecule #228. 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.)
When I was a graduate student, there were several professors in adjacent labs who had a profound impact on me. One of them was brilliant at developing new techniques to answer fundamental questions. Unfortunately, the time and effort required to stay at the top of his field took a toll on his marriage and his wife left him ... with the children.
Another professor made important contributions to his field because he was able to look at things from a different perspective. He taught me to be skeptical of "prevailing dogma." Fifteen years later he committed suicide by jumping off the roof of his lab.
Time and Careercast.com have compiled a list of the ten least stressful jobs in America [The 10 Least Stressful Jobs in America]. The subtitle says, "If your job requires frequent travel and strict deadlines it won't make the cut."
Job site CareerCast published a list of the least stressful jobs yesterday based on measurements of 11 specific factors across 200 occupations. The factors it considered are whether the job requires travel (the more travel, the higher the stress), growth potential (dead-end jobs tend to create more stress), strict deadlines, working in the public eye, competitiveness within the organization, physical demands, environmental conditions, putting your life at risk, hazards encountered, meeting the public, and having someone else’s life in your hands.
University Professor is #4 on the list.
Most of my colleagues are working 60 hours a week and most of them are preparing grants for the next "strict deadline." Their careers could be over if they can't get funding for their lab. If you don't think they are stressed, then I invite you to visit your local university and see for yourself. It's too bad that the people at Careercast.com didn't bother to do the research. It doesn't inspire confidence in their business.
Professors have become adept at finding the cheapest flights to conferences and meetings. Many of them have to balance their time away from home with their responsibilities as parents. But travel is an essential part of a Professor's job.
Some of my colleagues are skipping dinner with their families in order to finish reading the thesis for this week's Ph.D. oral. That's a deadline that can't be avoided and they have a responsibility to the student. We are very used to having the future lives and careers of students depend on us. We're used to it but that doesn't make it any less stressful.
Speaking of stress, I wonder how many people at Time magazine have ever taught a large class of undergraduates? "Working in the public eye" seems to be part of a Professor's job and I can guarantee you that it's stressful—especially after the mid-term grades have been posted. (There are times when it seems like you are "putting your life at risk" but I don't want to compare this with firefighters and police officers who are really putting their lives at risk.) Speaking of strict deadlines ... I have a lecture tomorrow so I shouldn't be wasting time on this blog. It's going to get a lot worse next month when I have a pile of essays to grade and get back to the students in a timely manner.
Oh, I almost forgot. Two of my colleagues are up for tenure this semester. If you don't get tenure, you will be fired and the prospects of getting another job are slim. No stress there, right?
In fairness, Careercast.com specified "University Professor (tenured)" as the job that made the list. Here's what they say ...
The long road to becoming a tenured university professor is certainly challenging, too. For those who achieve tenured status, however, the rewards include job stability—a huge plus in a turbulent economy—and lucrative prospects. The College and University Professional Association for Human Resources reports that in the 2012-13 school year, tenured professors earned on average from $82,363 for Baccalaureate programs to $115,579 annually at research institutions and many professors receive top benefits such as tuition reimbursement for family members.
But the greater reward is sharing knowledge with their students.
Ultimately, a job’s reward trumps all other factors, including stress.
It's true that tenured University Professors have a great deal of job security as long as they continue to perform adequately. It's also true that professors earn higher than average salaries. It goes without saying that for most good paying jobs there are costs and benefits and the benefits must outweigh the costs or else nobody would do the job. (Duh!)
I love my job. So do most tenured professors. That does not mean that the job is one of the least stressful jobs in America. It means that the "job's reward trumps all other factors, including stress." I dare say that most people would not be able to handle the stress experienced by my younger, tenured, colleagues. You don't get to be a professor if you can't handle stress.
I don't want to exaggerate the stress and difficulty of being a University Professor but I do want to attack the common idea that it's a cushy high-paying job that almost anyone could handle if they were lucky enough to get hired.
My granddaughter just turned four so it's time to learn about chemistry. Her first experiment was checking the pH of various household liquids. Here she is paying close attention to her Mom. Later on she got to mix things by herself. Read the full story—incuding where she teaches Mommy how to count—at: And so it begins.....SCIENCE.
The Canadian Broadcasting Corporation (CBC) aired an episode of The Fifth Estate on Friday night. I taped it and watched it yesterday between curling matches and the Canadian figure skating championships.1
The Fifth Estate program documents the shutting down of various government labs by the Conservative government of Stephen Harper. The title says it all: Silence of the Labs. Follow the link and you can watch the entire program. I highly recommend that you watch the first two minutes to get the gist of what's happening in Canada.
Here's part of the summary that appears on the CBC website ...
Scientists across the country are expressing growing alarm that federal cutbacks to research programs monitoring areas that range from climate change and ocean habitats to public health will deprive Canadians of crucial information.
"What’s important is the scale of the assault on knowledge, and on our ability to know about ourselves and to advance our understanding of our world," said James Turk, executive director of the Canadian Association of University Teachers.
In the past five years the federal government has dismissed more than 2,000 scientists, and hundreds of programs and world-renowned research facilities have lost their funding. Programs that monitored things such as smoke stack emissions, food inspections, oil spills, water quality and climate change have been drastically cut or shut down.
The fifth estate requested interviews with two senior bureaucrats and four cabinet ministers with responsibility for resources, the environment and science. All of those requests were denied.
On Tuesday, the fifth estate received a statement from the office of Greg Rickford, Minister of State for Science and Technology, and the Federal Economic Development Initiative for Northern Ontario.
"Our government has made record investments in science," it stated. "We are working to strengthen partnerships to get more ideas from the lab to the marketplace and increase our wealth of knowledge. Research is vibrant and flourishing right across the country."
But members of the scientific community disagree. CBC’s the fifth estate spoke to scientists across the country who are concerned that Canadians will suffer if their elected leaders have to make policy decisions without the benefit of independent, fact-based science.
The CBC is a crown corporation. That means it has to report to a branch of the government and some its Board of Directors are government appointees. A lot of its funding comes from the Federal Government.
You probably won't be surprised to learn that the CBC is also under attack from the Harper government. I don't think that pressure is going to diminish once Conservative MPs see this program.
[Photo Credit: I took this picture during a protest on Parliament Hill in July 2012. There are videos in the Fifth Estate program but I didn't see any glimpses of me of any of my friends.]
1. So many exciting things on television—one has to have priorities. I don't watch the Leafs any more.
Some of the articles that are published in Biochemistry and Molecular Biology Education (BAMBED) are a little bit difficult to understand. Here's one from the latest issue....
Laura Miralles, Paloma Moran, Eduardo Dopico and Eva Garcia-Vazquez (2013) DNA Re-EvolutioN: A game for learning molecular genetics and evolution. BAMBED 41:396-401 [doi: 10.1002/bmb.20734]
The abstract explains that the goal is to teach evolution.
Evolution is a main concept in biology, but not many students understand how it works. In this article we introduce the game DNA Re-EvolutioN as an active learning tool that uses genetic concepts (DNA structure, transcription and translation, mutations, natural selection, etc.) as playing rules. Students will learn about molecular evolution while playing a game that mixes up theory and entertainment. The game can be easily adapted to different educational levels. The main goal of this play is to arrive at the end of the game with the longest protein. Students play with pawns and dices, a board containing hypothetical events (mutations, selection) that happen to molecules, “Evolution cards” with indications for DNA mutations, prototypes of a DNA and a mRNA chain with colored “nucleotides” (plasticine balls), and small pieces simulating t-RNA with aminoacids that will serve to construct a “protein” based on the DNA chain. Students will understand how changes in DNA affect the final protein product and may be subjected to positive or negative selection, using a didactic tool funnier than classical theory lectures and easier than molecular laboratory experiments: a flexible and feasible game to learn and enjoy molecular evolution at no-cost. The game was tested by majors and non-majors in genetics from 13 different countries and evaluated with pre- and post-tests obtaining very positive results.
I would be embarrassed to present this game to students at the University of Toronto. It seems more suitable for adolescents who are just learning about evolution in high school.
What do you think? Is this a suitable class experience for students at your university?
The latest issue of Biochemistry and Molecular Biology Education (BAMBED) has a list of "Websites of Note." One of them is Memorize.com. Here's what the BAMBED says about this site ...
You may be impressed or appalled that this site reduces biochemistry to the basics for rote learning. Type biochemistry into the search box associated with Learn on the home page. You will then discover numerous pages created by individual students who have listed prompts and answers to help in their biochemistry studies. Mostly the tabulations of pathways and facts are excellent and accurate. Try Laura Wright's page at memorize.com/biochemistry-metabolism-1/laurawright. The memorization protocol is simple, but effective. After declaring that you have memorized a table you will be tested and at the prompt you answer mentally or on paper, not by entering an answer. You then get to reveal the answer and tell the program whether your recall was correct. Continue as required until all propositions are memorized and can be answered correctly. Pavlov and Skinner would endorse the approach. If a student is pestering with the question "what else can I do to prepare for the exam?" then recommending this site may be the answer.
I was more than a little surprised that an education journal would advertise such a site especially since ASBMB (American Society of Biochemistry and Molecular Biology has come out strongly in favor of concept driven teaching [see ASBMB Promotes Concept Driven Teaching Strategies in Biochemistry and Molecular Biology]. The last issue of BAMBED had a series of articles on the proper way to teach biochemistry.
Theme
Better BiochemistryA concept driven course is incompatible with rote memorization and regurgitation of facts. No respectable teacher—and no reader of BAMBED—should ever send students to the memorize.com website.
According to ASMBM the The five core concept categories are:
- Evolution
- matter and energy transformation
- homeostasis
- biological information
- macromolecular structure and function
While I disagree with the way the evolution concept is described [ASBMB Core Concepts in Biochemistry and Molecular Biology: Evolution], I agree that it is important to teach biochemistry from an evolutionary perspective. I'm interested in knowing how biochemistry is taught at other schools and that's why I often look at websites such as memorize.com where students post what they think is important.
What I see at memorize.com is appalling. It's clear that students who are posting there have taken courses that focus exclusively on rat liver metabolism and human biochemistry. There's no evolutionary approach visible in any of the student websites. Not only that, many of these students seem to be fixated on something called the "rate-limiting step" in various pathways. Where does that come from? Is there a textbook that teaches like that?
There are people out there who actually think that as soon as an undergraduate finishes a biochemistry course they become an expert. This is the only explanation for all the favorable references to biochemistry websites constructed by teenagers who don't even have an undergraduate degree. (Many of them are directed at pre-med students who are preparing for the MCAT.)
Let's look at a few things that Laura Wright (Oxford University, UK?) says on her page at memorize.com [Biochemistry - Metabolism 1].
The first box tells us where various pathways are located in the cell. Of course, we're talking about animal cells, not bacteria or plants (photosynthesis isn't mentioned). We learn that protein synthesis takes place in the "RER.". I had to look that up ... it means "rough endoplasmic reticulum." I'd love to know who taught her that. Only a small subset of proteins enter the endoplasmic reticulum. The vast majority of protein synthesis takes place in the cytoplasm.
Students taking a rote memorization course often have to memorize the number of ATP equivalents produced when glucose is oxidized to CO2. This number is 32 ATP equivalents in bacteria and less in eukaryotes. It depends on a number of estimates, especially the number of ATP equivalents produced when electrons from NADH pass through the membrane-associated electron transport system (should be 2.5). Laura Wright says,
32 from malate-aspartate shuttle (heart and liver) vs only 30 from glycerol-3P shuttle (muscle)
This is not what I teach in my textbook but the point is that the "correct" answer on a multiple choice test will not depend on what I think or what Laura Wright thinks. She thinks that the citric acid cycle produces 24 ATP equivalents, I think it produces 20 ATP equivalents, and who know what YOUR professor thinks.
If biochemistry is properly taught from concepts then every student would understand the problems with these estimates and would be able to explain the assumptions behind the calculations.
It's sad to see the sorts of things that students have to memorize. Apparently, many of them have to memorize the names of metabolic diseases (e.g. Niemann-Pick disease) and the symptoms. I think they're also expected to memorize the names of enzymes.
This is not how biochemistry should be taught.
The Clergy Letter Project is sponsoring the 9th annual "Evolution Weekend" on February 7-0 2014. This is a weekend where clergy talk to their congregations about science and evolution. Here's how they describe the event ...
Evolution Weekend is an opportunity for serious discussion and reflection on the relationship between religion and science. An ongoing goal has been to elevate the quality of the discussion on this critical topic, and to show that religion and science are not adversaries. Rather, they look at the natural world from quite different perspectives and ask, and answer, different questions.
Maybe it's just me, but I thought that "serious discussion and reflection" means that all aspects of the conflict between science and religion would be considered. This includes the possibility that the conflict is very real and cannot be accommodated.
I was wrong. If you are a member of the Clergy Letter Project your mind is already made up.
Because religion and science use different methodologies to understand the world, and because religion and science ask very different questions, there is no reason to view them in conflict. One important facet of Evolution Weekend 2014, therefore, is to explore the questions each ask and to examine the different ways of knowing embodied in each.
There's not going to be any serious discussion about different ways of knowing and which ones are successful.
One of the most important lessons of science is that life evolved from simple primitive organisms over a period of at least three billion years. The history of life can be fully explained by natural causes without any need for miracles or divine intervention. We have learned that the evolution of life on this insignificant planet, in an ordinary galaxy, in a vast universe, has no purpose or goal.
There aren't many religions that can accommodate those facts.
[Hat Tip: Panda's Thumb]
My department is in a Faculty of Medicine and the main source of research funding for biomedical sciences in Canada is the Canadian Institutes of Health Research (CIHR). The current Conservative Government has been consistently underfunding CIHR over the past six years so that the number of grants available for basic research (e.g. biochemistry and molecular biology) has been falling.
This is the time of the year when my colleagues hear the results of the latest grant competitions. It's been a sad couple of days because four labs failed to get funding for their main research projects. Eight other labs failed to get additional funding for ongoing projects that were not part of their main grant.
What does this mean? Let's think about the consequences for labs that lose their grants. In the short term, the lab will survive until the next application deadline but it means that the Professor running the lab can't take on any new graduate students or post-docs no matter how brilliant they might be. In some cases, the department, or the university, might have to provide "bridging" funds in order to pay the salaries and stipends of people in the lab. If the Professor manages to get the grant back in the next competition then a recovery is possible but a lot of damage has already been done.
However, in many cases the second or third attempts to recover funding are not successful and the lab must shut down. That's the situation we face in our department with several active research groups that have disappeared or are about to disappear.
The first people to be let go are the post-docs who are funded from the grant. They have to scramble to find a new position and this isn't easy. It could be the end of their career.
The most expensive people in the lab are the research technicians ($50-60,000 per year1). They have to be put on notice and they will be fired. These are scientists with advanced degrees who are the heart and soul of a research lab. They are mostly women in mid-career. Many of them will never find another position that pays as well.
Graduate students who are close to finishing can usually be helped but those at the beginning of their studies have to switch to another lab and start a new project. This may not be possible.
Our research labs have two or three undergraduate students doing research projects as part of their degree requirements. As we lose more and more active labs, we also lose the ability to train undergraduates. We also hire undergraduate to work in labs over the summer and this provides invaluable experience in preparation for graduate school. If you don't have a funded lab you can't hire students. If you lose part of your funding, the easiest way to save money is not to hire anyone.
The groups that are losing their grants are the backbone of Canadian research infrastructure. The typical lab has three or four graduate students, a post-doc, and a research technician (research associate, lab manager). It takes about $150,000 per year to sustain such a lab. The Professor who runs the lab is usually between 30 and 40 years old (mid-career). The lab is producing several papers a year in respectable journals. These labs would easily have been funded a decade ago when the success rate on grant applications was 25% but now that it's down to 15% they are being cut out of the system.
Even those labs that are still funded are affected when a colleague loses a grant. That's because there's a lot of sharing of equipment and resources and expertise. We can foresee a time when the department falls below a critical mass of active research labs and when that happens everyone will lose their grants. Morale is already at an all-time low. Students and faculty are more worried about survival than science.
A generation of mid-career scientists is being destroyed by the policies of the Canadian government. Graduate students, post-docs, technicians, and undergraduates are being affected. It might take another generation to recover if funding were to return to appropriate levels. We might never recover if something isn't done soon.
Here at the University of Toronto we used to talk about becoming a world-class research centre. We don't talk about that very much any more.
1. Salary plus benefits.
