More Recent Comments

Thursday, January 08, 2015

Evolutionary biochemistry and the importance of random genetic drift

I urge you to read an important paper that has just been published in PNAS.
Lynch, M., Field, M.C., Goodson, H.V., Malik, H.S., Pereira-Leal, J.B., Roos, D.S., Turkewitz, A.P., and Sazer, S. (2014) Evolutionary cell biology: Two origins, one objective. Proc. Natl. Acad. Sci. (USA) 111:16990–16994. [doi: 10.1073/pnas.1415861111]
Here's the bit on random genetic drift. It will be of interest to readers who have been discussing the importance of drift and natural selection in a previous thread [How to think about evolution].

Do you think Lynch et al. are correct? I do. I think it's important to emphasize the role of random genetic drift and I think it's true that most biochemists and cell biologists are stuck in an adaptationist mode of thinking.
A commonly held but incorrect stance is that essentially all of evolution is a simple consequence of natural selection. Leaving no room for doubt on the process, this narrow view leaves the impression that the only unknowns in evolutionary biology are the identities of the selective agents operating on specific traits. However, population-genetic models make clear that the power of natural selection to promote beneficial mutations and to remove deleterious mutations is strongly influenced by other factors. Most notable among these factors is random genetic drift, which imposes noise in the evolutionary process owing to the finite numbers of individuals and chromosome architecture. Such stochasticity leads to the drift-barrier hypothesis for the evolvable limits to molecular refinement (28, 29), which postulates that the degree to which natural selection can refine any adaptation is defined by the genetic effective population size. One of the most dramatic examples of this principle is the inverse relationship between levels of replication fidelity and the effective population sizes of species across the Tree of Life (30). Reduced effective population sizes also lead to the establishment of weakly harmful embellishments such as introns and mobile element insertions (7). Thus, rather than genome complexity being driven by natural selection, many aspects of the former actually arise as a consequence of inefficient selection.

Indeed, many pathways to greater complexity do not confer a selective fitness advantage at all. For example, due to pervasive duplication of entire genes (7) and their regulatory regions (31) and the promiscuity of many proteins (32), genes commonly acquire multiple modular functions. Subsequent duplication of such genes can then lead to a situation in which each copy loses a complementary subfunction, channeling both down independent evolutionary paths (33). Such dynamics may be responsible for the numerous cases of rewiring of regulatory and metabolic networks noted in the previous section (34, 35). In addition, the effectively neutral acquisition of a protein–protein-binding interaction can facilitate the subsequent accumulation of mutational alterations of interface residues that would be harmful if exposed, thereby rendering what was previously a monomeric structure permanently and irreversibly heteromeric (8, 36–39)1. Finally, although it has long been assumed that selection virtually always accepts only mutations with immediate positive effects on fitness, it is now known that, in sufficiently large populations, trait modifications involving mutations with individually deleterious effects can become established in large populations when the small subset of maladapted individuals maintained by recurrent mutation acquire complementary secondary mutations that restore or even enhance fitness (40, 41).


1. Note the brief description of how irreversibly complex structures can evolve. This refutes Michael Behe's main point, which is that irreversibly complex structures can't have arisen by natural processes and must have been designed. We've known this even before Darwin's Black Box was published.

Wednesday, January 07, 2015

The problem of the origin of life has been solved and creationists are terrified

You learn something new every day. Today I learned that a young physics professor at MIT has figured out how life originated without god(s). Salon let's us know about this amazing discovery: God is on the ropes: The brilliant new science that has creationists and the Christian right terrified.
The Christian right’s obsessive hatred of Darwin is a wonder to behold, but it could someday be rivaled by the hatred of someone you’ve probably never even heard of. Darwin earned their hatred because he explained the evolution of life in a way that doesn’t require the hand of God. Darwin didn’t exclude God, of course, though many creationists seem incapable of grasping this point. But he didn’t require God, either, and that was enough to drive some people mad.

Darwin also didn’t have anything to say about how life got started in the first place — which still leaves a mighty big role for God to play, for those who are so inclined. But that could be about to change, and things could get a whole lot worse for creationists because of Jeremy England, a young MIT professor who’s proposed a theory, based in thermodynamics, showing that the emergence of life was not accidental, but necessary. “[U]nder certain conditions, matter inexorably acquires the key physical attribute associated with life,” he was quoted as saying in an article in Quanta magazine early in 2014, that’s since been republished by Scientific American and, more recently, by Business Insider. In essence, he’s saying, life itself evolved out of simpler non-living systems.
Jerremy England's ideas are too complex for me. Watch this video to see for yourself.



Should politicians and lawyers ban the teaching of some subjects in public schools?

The Scottish Secular Society (SSS) was upset that creationism might be slipping into some schools in Scotland. They petitioned the Scottish government requesting that teaching creationism be banned in public schools in Scotland.1 Government officials refused on the grounds that there were already mechanisms in place to ensure that students received a proper science education [Schools creationism ban rejected by Scottish Government].

The official said,
Safeguards include; school managers having oversight of curriculum planning and resources; local authorities with robust complaints procedures, independent school inspections and the development of curriculum materials through a collegiate approach that provides for early identification of any inappropriate material.
This seems like the proper approach to me. Governments can set up mechanisms to create standardized curricula and that should include descriptions of what should be taught in each grade. They can even pass a law saying that all schools have to adhere to the guidelines.

I don't think they should be responding to pressure groups that want to ban the teaching of certain subjects. Most of us would react strongly to any government that banned teaching of sex education, evolution, communism, Islamic culture, feminism, gun control, or post-modernism.2 We should also be wary of banning other subjects even though we are certain that they are wrong—subjects such as Young Earth Creationism. If you give politicians the right to ban teaching of certain subjects then don't be surprised if it backfires.

It's best not to give them that power in the first place but to rely instead on curricula and standards that are developed by educators and enforced by educators. Mistakes will be made but it's better in the long run to do it that way than to have education influenced by the power of lobbyists and pressure groups and petitions.

Jerry Coyne disagrees. He thinks that the Scottish government should have banned the teaching of creationism [Scotland refuses to ban teaching of creationism]. This is one of those issues where Jerry and I strongly disagree. He wants to fire teachers who teach creationism and he wants government to pass and enforce laws that prohibit the teaching of certain subjects.

Here's the letter he wrote to Fiona Robertson, the director of Scotland’s Learning Directorate.
Dear Ms. Robertson,

As an American professor who teaches evolutionary biology, I was deeply disappointed to read in The Herald of Scotland that your country’s education directors refuse to ban the teaching of creationism to schoolchildren....

As the author of a popular book on the evidence for evolution (Why Evolution is True), I am fully aware of the massive evidence for evolution and the complete absence of evidence for any creationist views, which invariably stem from Biblical literalism. Creationism is thus a purely nonscientific view based on religion, and I’m saddened that Scotland won’t take even a minimal stand to ensure that its children are not indoctrinated with such bogus "science". The truth of evolution, I’ve found, is not only fascinating, based as it is on mountains of diverse but congruent evidence, but also deeply enlightening, showing us how our own species, and other species as well, came to be. It is the true story of our origins.

I hope that Scotland, like England and Wales, will have the resolve to explicitly establish some guidelines about what Tim Simmons, head of the Curriculum Unit, called "well-established science." Without an explicit statement that creationism is not well-established science, schools are at the mercy of whatever their teachers want to impart about the origins and diversity of organisms.

Thank you for your consideration.
Cordially,
Jerry Coyne
Professor
Department of Ecology and Evolution
The University of Chicago
Chicago, IL 60637 USA
I don't agree with Jerry Coyne. I'm all in favor of teaching evolution and proper science but I'm also in favor of teaching students why things like creationism, astrology, and homeopathy are wrong and why the Loch Ness monster doesn't exist.

It's a bit ridiculous to pass laws banning the teaching of every single thing that "is not well-established science."

It's true that "schools are at the mercy of whatever their teachers want to impart" but the way to fix that problem is to change the views of society, and teachers, about evolution and creationism. There isn't much evidence that simply banning certain subjects will actually change whether students believe them or not. If that were true, then we would expect that the students of Dover Pennsylvania have now come to accept evolution and reject creationism.


1. I'm using "public" school in the North American sense to refer to schools that are open to the public and supported by government funding.

2. I'm a bit ambivalent about banning post-modernism.

Tuesday, January 06, 2015

The textbooks are wrong about protein synthesis according to a press release from the University of Utah

A recent paper in Science provides evidence that when protein synthesis is stalled a protein called Rqc2 ("conserved from yeast to man") catalyzes the addition of random amounts of alanine and threonine the the C-terminus of the proteins that's about to be destroyed (Shen et al., 2015).

Here's the editorial summary of the work ...
During the translation of a messenger RNA (mRNA) into protein, ribosomes can sometimes stall. Truncated proteins thus formed can be toxic to the cell and must be destroyed. Shen et al. show that the proteins Ltn1p and Rqc2p, subunits of the ribosome quality control complex, bind to the stalled and partially disassembled ribosome. Ltn1p, a ubiquitin ligase, binds near the nascent polypeptide exit tunnel on the ribosome, well placed to tag the truncated protein for destruction. The Rqc2p protein interacts with the transfer RNA binding sites on the partial ribosome and recruits alanine- and threonine-bearing tRNAs. Rqc2p then catalyzes the addition of these amino acids onto the unfinished protein, in the absence of both the fully assembled ribosome and mRNA. These so-called CAT tails may promote the heat shock response, which helps buffer against malformed proteins
This is mildly interesting. We've known about ubiquitin ligase for decades but this is a different way of tagging proteins for destruction.

We'll have to see if this work stands up to verification but even if it does, it's not going to make it into the textbooks.

Let's see what the University of Utah Press Office has to say ...
Defying Textbook Science, Study Finds New Role for Proteins

Open any introductory biology textbook and one of the first things you’ll learn is that our DNA spells out the instructions for making proteins, tiny machines that do much of the work in our body’s cells. Results from a study published on Jan. 2 in Science defy textbook science, showing for the first time that the building blocks of a protein, called amino acids, can be assembled without blueprints – DNA and an intermediate template called messenger RNA (mRNA). A team of researchers has observed a case in which another protein specifies which amino acids are added.

"This surprising discovery reflects how incomplete our understanding of biology is,” says first author Peter Shen, Ph.D., a postdoctoral fellow in biochemistry at the University of Utah. “Nature is capable of more than we realize." ...
Mathew Cobb, writing on Jerry Coynes blog, explains why this isn't really a big deal [CAT tails weaken the central dogma – why it matters and why it doesn’t]. Let me just add that the synthesis of peptides with defined sequences in the absence of mRNA and ribosomes has been described in most textbooks since the 1980s. The best examples are the peptides involved in pepditogylcan synthesis (cell walls) and peptide antibiotics.

Here's a figure from my book.


What this means is that the statement, "... showing for the first time that the building blocks of a protein, called amino acids, can be assembled without blueprints – DNA and an intermediate template called messenger RNA (mRNA)" is simply not true.

We really, really, need to do something about university press releases.


Shen, P.S., Park, J., Qin, Y., Li, X., Parsawar, K., Larson, M.H., Cox, J., Cheng, Y., Lambowitz, A.M., Weissman, J.S., Brandman, O., and Frost, A. Rqc2p and 60S ribosomal subunits mediate mRNA-independent elongation of nascent chains. Science 347:75-78. [doi: 10.1126/science.1259724 ]

Guilt by association

There are many common fallacies that can easily make your argument invalid. The Intelligent Design Creationists seem to posses an uncanny ability to use each and every one of them. Here's a good example of guilt by association, heavily laced with ad hominem.

It's a documentery called The Biology of the Second Reich) by John West and colleagues. John West is one of the bigwigs at the Discovery Institute. The IDiots see this sort of propaganda as support for Intelligent Design Creationism and evidence against evolution.


The IDiots are excited about the fact that this documentary just won a prize in the "Best Documentary Short" category of the Los Angeles Cinema Festival of Hollywood! [Congratulates to John West as Biology of the Second Reich, "Best Documentary Short," Scores Big Recognition!]. I'm pretty sure the prize is based on the quality of the production and not on the accuracy of the information in the documentary. This is typical of most awards for documentaries and nonfiction books.


Monday, January 05, 2015

If you take away religion, you can't hire enough police

Here's a Harvard Professor, Clayton Christensen, telling us with a straight face that democracy in the USA requires religion because in the absence of religion people won't choose to obey laws. He ends with, "If you take away religion, you can't hire enough police."

It makes me wonder how much critical thinking goes on in his classes at Harvard Business School. Do Harvard students let him get away with this crap?



Sunday, January 04, 2015

A lesson on genetic load

The genetic load argument is one of the five things you should know if you are going to participate in the junk DNA debate.

Dan Graur has written an excellent summary of the genetic load argument from the perspective of population genetics. He links to it from his blog: If @ENCODE_NIH is right, each of us should have 7 x 1045 children.

Read it.


Is that really all they've got?

Last week I alerted you to seven of the top ten evolution stories according to IDiots [Is that all they've got?. Now it's time for the top three stories .... hang on to your hats.

#3. #3 of Our Top Ten Evolution Stories of 2014: Cosmos Finale Takes One Last Shot at the Privileged Planet Thesis

#2. #2 of Our Top Ten Evolution Stories of 2014: Now with More Doubt! Meyer's Landmark Is Back in a New Edition, Replying to the Critics

And the number one proof of Intelligent Design Creationism in 2014 is ....

#1. Happy New Year! Our #1 Evolution Story of 2014: New Paper from Biologic Institute, "Shared Evolutionary History or Shared Design?"

At this rate real, science will probably survive through most of 2015.


A physiologist thinks about evolution

Denis Noble is a physiologist at Oxford University (now Professor Emeritus). He is famous for his work on the physiology of the heartbeat and he is touted as one of the founders of systems biology.

Denis Noble wrote a book on evolutionary theory called The Music of Life. It's featured on The Third Way, a website created by James Shapiro to promote his version of a paradigm shift in thinking about evolution. All the usual suspects are represented on that site.1

Here's how the book is described on that website ....
What is Life? Decades of research have resulted in the full mapping of the human genome - three billion pairs of code whose functions are only now being understood. The gene’s eye view of life, advocated by evolutionary biology, sees living bodies as mere vehicles for the replication of the genetic codes.

But for a physiologist, working with the living organism, the view is a very different one. Denis Noble is a world renowned physiologist, and sets out an alternative view to the question - one that becomes deeply significant in terms of the living, breathing organism. The genome is not life itself. Noble argues that far from genes building organisms, they should be seen as prisoners of the organism.

The view of life presented in this little, modern, post-genome project reflection on the nature of life, is that of the systems biologist: to understand what life is, we must view it at a variety of different levels, all interacting with each other in a complex web. It is that emergent web, full of feedback between levels, from the gene to the wider environment, that is life. It is a kind of music.

Including stories from Noble’s own research experience, his work on the heartbeat, musical metaphors, and elements of linguistics and Chinese culture, this very personal and at times deeply lyrical book sets out the systems biology view of life.
I haven't read this book and I don't intend to read it. Having listened to a lecture by Denis Noble (below) I don't think I'm going to learn anything more by buying the book.

I urge you to watch the lecture. It's the plenary lecture at the International Conference of Physiological Sciences in November, 2012. Denis Noble is the President of the International Union of Physiological Sciences. The lecture is only 30 minutes long but it gives you a good introduction to the way many scientists from outside the field of evolutionary biology are thinking about evolution (and the Central Dogma of Molecular Biology). It's not a very pretty picture.


If you want a brief summary of what's wrong with this lecture see Jerry Coyne's blog website post: Famous physiologist embarrasses himself by claiming that the modern theory of evolution is in tatters.


1. For more on James Shapiro see: The Third Fourth? Way
Evolution: a View from the 21st century
Reply to Laurence A Moran’s review of Evolution: A View from the 21st Century
James Shapiro Responds to My Review of His Book
James Shapiro Never Learns
James Shapiro Claims Credit for Predicting That Junk DNA Is Actually Part of a "highly sophisticated information storage organelle"
Revisiting the Central Dogma in the 21st Century.

Saturday, January 03, 2015

Thinking critically about the Central Dogma of Molecular Biology

Our department is preparing to review our undergraduate courses and programs. Part of the review will be to examine our fundamental goals and objectives and determine if we are meeting them. In preparation for this exercise, I've been going over some papers that have been sitting around my office.

One of them concerns teaching the Central Dogma of Molecular Biology (Wright et al., 2014). It was just published last year. The authors have discovered that students have a "weak conceptual understanding" of information flow. Here's how they describe it in the abstract.
The central dogma of molecular biology, a model that has remained intact for decades, describes the transfer of genetic information from DNA to protein though an RNA intermediate. While recent work has illustrated many exceptions to the central dogma, it is still a common model used to describe and study the relationship between genes and protein products. We investigated understanding of central dogma concepts and found that students are not primed to think about information when presented with the canonical figure of the central dogma. We also uncovered conceptual errors in student interpretation of the meaning of the transcription arrow in the central dogma representation; 36% of students (n = 128; all undergraduate levels) described transcription as a chemical conversion of DNA into RNA or suggested that RNA existed before the process of transcription began. Interviews confirm that students with weak conceptual understanding of information flow find inappropriate meaning in the canonical representation of central dogma. Therefore, we suggest that use of this representation during instruction can be counterproductive unless educators are explicit about the underlying meaning.

Thursday, January 01, 2015

Most popular Sandwalk post in 2014

Lot's of people are publishing year-end summaries of their blog activity. It got me to wondering which of my posts was the most popular in 2014.

The result was a surprise ...

August 18, 2014: John Wilkins discusses the "Demarcation Problem"
One of the most fascinating things about philosophy is the fact that philosophers still can't agree on the major issues even after debating them for hundreds of years. For example, they still can't, as a discipline, agree on whether there are good arguments for the existence of gods. Many universities have theologians who masquerade as philosophers and publish in philosophy journals....

Tuesday, December 30, 2014

What do you do in Los Angeles in February?

I've visited Los Angeles in February. There are lots of cool things you can do, like going to the beach with your granddaughter or spending a day at Disneyland. I won't be there this February and that's a shame because I'll be missing an important event [Things to do in LA in February].
Bad Biology: How Adaptationist Thinking Corrupts Science

11 a.m., Sun., Feb. 15 – Hollywood; 4:30 p.m. – Costa Mesa

In 1979, Gould and Lewontin published an important paper, “The Spandrels of San Marco and the Panglossian Paradigm: A Critique of the Adaptationist Programme”, in which they deplored the narrow focus on seeing evolution as only a process of adaptation. They further criticized the field of evolutionary biology for perpetuating this pattern of flawed thinking.

Biologist PZ Myers bemoans that their warnings have gone unheeded in some biological sub-disciplines. He’ll be discussing a few examples of bad evolutionary biology, including the “human biodiversity” movement that is little more than a collection of pseudoscientific rationalizations for racism; evolutionary psychology, which seeks to explain modern human biology with imaginary scenarios of adaptive constraints from 10,000 years ago; and the ENCODE project, which was an obvious and overt exercise in adaptive bias applied to genomic data. A common thread among these examples is an excessive reliance on adaptationist thinking and a lack of appreciation of the diversity of mechanisms underlying our evolutionary history.
Don't miss it if you are anywhere near Los Angeles this February.


Simulated meteorite impact produces RNA bases. So what?

A group of Czech scientists have fired a big laser at a solution of formamide and found traces of adenine, guanine, cytosine, and uracil (Ferus et al., 2014). The result is reported in an article in Science [From hell on Earth, life's building blocks]. The image is from the Science article.

Here's the abstract of the PNAS article ...
The coincidence of the Late Heavy Bombardment (LHB) period and the emergence of terrestrial life about 4 billion years ago suggest that extraterrestrial impacts could contribute to the synthesis of the building blocks of the first life-giving molecules. We simulated the high-energy synthesis of nucleobases from formamide during the impact of an extraterrestrial body. A high-power laser has been used to induce the dielectric breakdown of the plasma produced by the impact. The results demonstrate that the initial dissociation of the formamide molecule could produce a large amount of highly reactive CN and NH radicals, which could further react with formamide to produce adenine, guanine, cytosine, and uracil. Based on GC-MS, high-resolution FTIR spectroscopic results, as well as theoretical calculations, we present a comprehensive mechanistic model, which accounts for all steps taking place in the studied impact chemistry. Our findings thus demonstrate that extraterrestrial impacts, which were one order of magnitude more abundant during the LHB period than before and after, could not only destroy the existing ancient life forms, but could also contribute to the creation of biogenic molecules.
In case you don't appreciate the significance of this research, PNAS provides you with a brief summary ...
This paper addresses one of the central problems of the origin of life research, i.e., the scenario suggesting extraterrestrial impact as the source of biogenic molecules. Likewise, the results might be relevant in the search of biogenic molecules in the universe. The work is therefore highly actual and interdisciplinary. It could be interesting for a very broad readership, from physical and organic chemists to synthetic biologists and specialists in astrobiology.
The problem with all these studies is that they don't answer the most important question; what happens next?

Let's assume that the four bases were created in the atmosphere as meteorites crashed into Earth four billion years ago. Let's assume there was water in the form of early oceans or big lakes. Then what happens? Do these researchers imagine that the concentrations of these bases built up gradually over thousands of years until there were spontaneous reactions with five-carbon sugars and phosphate to form nucleotides? Then did these nucleotides assemble into short RNA molecules?

It's a very large step from demonstrating that RNA bases can be made from formamide under extreme conditions to showing that their concentrations could have been high enough to make RNA spontaneously.

We need to demand more of these researchers. If they are going to postulate that life arose in a primordial soup then it's no longer sufficient to publish one more paper on how you can make organic molecules from inorganic precursors. Enough already. That's the easy part of the hypothesis. Let's see some evidence for the hard part.


Ferus, M., Nesvorný, D., Šponer, J., Kubelík, P., Michalčíková, R., Shestivská, V., Šponer, J.E., and Civiš, S. (2014) "High-energy chemistry of formamide: A unified mechanism of nucleobase formation." Proceedings of the National Academy of Sciences Published online before print December 8, 2014. [doi: 10.1073/pnas.1412072111]

Sunday, December 28, 2014

How do we teach our students that basic research is important?

There's a fabulous editorial in the Toronto Star today. It's critical of the Prime Minister and the Conservative Party of Canada for the damage they are doing to science in Canada [Canada needs a brighter federal science policy: Editorial].

Here's some excerpts ...
Finding a fan of Canada’s current science policy among those who care about such things would be a discovery worthy of Banting and Best. Few if any would contend that Ottawa’s approach is sound; rather, the debate in 2014 has been over what in the world would possess a government to pursue such a catastrophic course.

According to one school of thought, the answer is simple: the Conservatives are cavemen set on dragging Canada into a dark age in which ideology reigns unencumbered by evidence. Let’s call this the Caveman Theory.

The other, more moderate view holds that Prime Minister Stephen Harper et al are not anti-science – that they at least understand the importance of research and development to their "jobs and growth" agenda – but are instead merely confused about how the enterprise works and about the role government must play to help it flourish. Let’s call this the Incompetence Theory.
The rest of the editorial describes how Stephen Harper and his Conservative buddies have directed funding agencies to concentrate on research that will be of direct benefit to Canadian for-profit companies.

It concludes with ...
Whatever the government’s motives, whatever it understands or does not about how science works, it has over the last eight years devastated Canadian research in a way that will be hard to reverse. Private sector R&D continues to lag, but in our efforts to solve that problem we have seriously reduced our capacity for primary research, squandering a long-held Canadian advantage. Meanwhile, we have earned an international reputation for muzzling scientists, for defunding research that is politically inconvenient and for perversely conflating scientific goals with business ones, thus dooming both. Our current funding system is less well placed than it was in 2006 to promote innovation and our science culture has been so eroded that we are unlikely to attract the top talent we need to compete in the knowledge economy.

Whether it was anti-intellectualism, incompetence or both that led us to this dark place, let this coming election year bring the beginning of a climb back into the light.
How can the government of Canada be so ignorant? It's because they have a huge amount of support from the general public who see all research as technology. They are only willing to support research that helps the economy.

Most people are not interested in research that simply advances our knowledge of the natural world.

What are we doing as educators to reverse this trend? Not very much, as it turns out. Many of our courses in biochemistry focus on how biochemistry can benefit medicine as though this was the only reason for learning about biochemistry.1 Our department is discussing whether we should have undergraduate courses on drug discovery and how drugs are brought to market. We are considering a co-op program where students will spend some time working in the private sector. We are toying with the idea of creating an entirely new program that will train students to work in the pharmaceutical industry.

It's no wonder that the general public thinks of science as the servant of industry. We are not doing a very good job of teaching undergraduates about the importance of knowledge and the value of scientific thinking. In fact, we are doing the opposite. We are supporting the Stephen Harper agenda.

Don't be surprised if it comes back to bite you in the future.


1. We teach medical case studies in our introductory biochemistry course for science undergraduates!