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Friday, July 19, 2013

Speaking of Trees

My friends and colleagues, David Isenman and Jacqueline Segall, used to have a big tree in their back yard. On Monday July 8th it rained ... a lot. The ground became very soggy and the tree tipped over.

So much for the life of this tree. They need a new shed.



What Is Humanism?

What the heck is humanism? The short answer is ... I have no idea.

If someone tells me they're a humanist then I can guess that they have some kind of ethical standards that have nothing to do with religion but that's about all I can guess. They might as well have told me that they are an atheist and leave it at that.

Are humanists socialists? Do they all favor socialized medicine and support unions? Do they oppose the death penalty? Are they in favor of gun control and abortion on demand? Do humanists oppose the American war in Afghanistan? Did they support the invasion of Iraq?

Are humanists willing to vote for a Republican or a Conservative? How about a Communist? Do all humanists think gay marriage should be legal? Would they legalize prostitution and pornography? Would they legalize drugs like cocaine and marijuana? How do they feel about euthanasia?

Do humanists support a public school system or are some in favor of vouchers and private schools? Do they all have the same position on immigration? on welfare?

I don't know the answer to any of these questions. I don't know what it means to be a humanist.

Hermant Mehta thinks that Humanism tells us what he believes. Watch this video to see what that means.


Still confused? Go to the American Humanist Association website and you'll be even more confused. Read the Humanist Manifesto and the essays by Fred Edwords. They don't answer any of the questions I asked.


How to Build a Research Institute


The Francis Crick Institute is under construction in London (UK). When I first heard about this I thought that it would be a wonderful place for theoretical biologists—a sort of Institute for Advanced Study for biologists. That would be in keeping with the career of Francis Crick. It's also something that sorely needed in the 21st century because most biology has degenerated into data collection and mining with little attention to ideas and concepts.

Alas, the director, Paul Nurse, had other ideas. He wanted to create "a world-leading centre of biomedical research and innovation." In other words, translation research.

Paul Nurse and two research directors (Richard Treisman and Jim Smith) wrote an editorial in a recent issue of Science [Building Better Institutions]. They take it as a given that what Great Britain needs is a research institute that concentrates on medical research. They also believe that mixing scientists, clinicians, and representatives of the pharmaceutical industry will lead to better results. You better throw in a few physical scientists for good measure because physical scientists have good ideas.
Despite the recent growth in scientific knowledge, conventional discipline-based methods have not been suffi ciently effective at developing new understanding and treatments. Researchers need to be encouraged to identify important questions and tackle them with multidisciplinary approaches. Contemporary biomedical research has to integrate biological, nonbiological, and clinical disciplines, and its application requires interactions with hospital and commercial partners. This can be facilitated by research institutions with an environment that supports strong interdisciplinary interactions between scientists: a place where laboratory biologists are encouraged to collaborate with clinical researchers to understand the medical implications of their work, with pharmaceutical companies for the translation of discoveries into treatments, and with physical scientists to expand their thinking and repertoire of experimental approaches. Such an institution must be continually open to new ideas and permeable to interactions with outside researchers and organizations.
We've been doing exactly that at our hospital research institutes here at the University of Toronto. The industrial relationship has been helped by something we call the MaRS Discovery District. The experiment has been running for over a decade and, as I'm sure you all know, it has been hugely successful. Toronto has been churning out new medical discoveries on a daily basis. (Not!)

The Francis Crick Institute will support young investigators because scientists at the beginning of their career have such a tremendous track record of creativity and originality. (?) In fact, the new institute believes so strongly in young investigator that 80 out of 120 positions will be set aside for them. But what happens when they reach their mid-forties?
These appointments will be of up to 12 years, supported by the Crick's funding partners (the Medical Research Council, Cancer Research UK, and the Wellcome Trust). Group leaders will then leave the institute to establish a research group elsewhere; the aim is to give researchers who are effective and remain in the United Kingdom a transition package to support their moves, creating a thriving network of highly trained researchers.
Science is a risky business so every year there will likely be three or four investigators whose time is up but whose scientific output is just average. What happens when they're tossed out of the institute?

Does anyone think this is a good idea?


What Should We Teach About the "Tree of Life"?

As most of you already know, I think the Three Domain Hypothesis is dead. The history of life is better explained as a net with rampant transfer of genes between species [The Web of Life]. This idea has been widely promoted by Ford Doolittle.

The debate over the tree of life has implications concerning the distinction between "prokaryote" and "eukaryote." I was checking some recent papers and came across one by Doolittle and Zhaxybayeva (2013) that seems particularly relevant. They discuss the evidence for and against the division of life into three domains and the attempt by Norm Pace to ban the word "prokaryote."

The authors point out, once again, that eukaryotic genes are most closely related to genes from cyanobacteria, proteobacteria, and archaebacteria, in that order. The majority, by far, have their closest homologs in bacteria, not archaebacteria. The most likely explanation is that euakryotes are chimeras resulting from fusion of an archaebacterium and a eubacterium plus genes transferred from mitochondria and chloroplast to the nuclear genome.

Thursday, July 18, 2013

The Largest Prokaryotic Genomes

Some bacterial genomes are quite large. A few are larger than the smallest eukaryotic genomes.

Many species of cyanobacteria are complex, multicellular organisms [Multicellular Bacteria]. Those species tend to have large genomes.

Recently Degan et al. (2013) sequenced the genomes of six new cyanobacteria species and one of them turns out to have a large genome.1 (see Contradictory Phylogenies for Cyanobacteria for more information on that paper.) The species is Scytonema hofmanni and its genome is 12,073,012 bp in size. It has 12,356 potential protein-coding genes. If all of them are correctly identified then the total, counting non-protein-coding genes, is likely to be 12,500 genes. That's a record for prokaryotes.

Half of these genes are only found in Scytonema and that's very strange.

There are bacteria with larger genomes, notably the soil bacterium Ktedonobacter racemifer with a genome size of 13,661,586 bp.

For comparison, the genome of the yeast, Saccharomyces cerevisiae, is 12,156,677 bp in size and it has 6,200 genes.


Photo Credit: Scytonema hofmanni from cyanobacteria slides.

1. Some of you might be under the impression that I give a shit about Norm Pace and his attempt to banish the word "prokaryote" (Pace, 2009). Don't bother to try and convince me because it requires that I accept the false Three Domain Hypothesis and that ain't gonna happen.

Dagan, T., Roettger, M., Stucken, K., Landan, G., Koch, R., Major, P., Gould, S. B., Goremykin, V.V., Rippka, R., de Marsac, N.T., Gugger, M., Lockhart, P.J., Allen, J.F., Brune, I., Maus, I., Pühler, A. and Martin, W.A. (2013) Genomes of stigonematalean cyanobacteria (Subsection V) and the evolution of oxygenic photosynthesis from prokaryotes to plastids. Genome biology and evolution 5:31-44.
[doi: 10.1093/gbe/evs117]

Pace, N.R. (2009) Time for a change. Nature 441:289. [doi:10.1038/441289a]

Contradictory Phylogenies for Cyanobacteria

The cyanobacteria are interesting for a number of reasons. They have a complex photosynthesis pathway with two separate phostosystems and an oxygen evolving complex. That means they can use water as an electron donor and NADP as an electron acceptor.

Cyanobacteria probably played an important role in creating an atmosphere with significant levels of oxygen but, contrary to some speculation, they almost certainly arose fairly late in the history of life (i.e. after 500 million years). Cyanobacteria make up a significant proportion of life in the ocean. Primitive cyanobacteria gave rise to chloroplasts in modern plants and algae.

The Shortest Distance ....

I have many pet peeves. One of them concerns the people who build paths and walkways. If you're going to spend a lot of money constructing fancy walkways, then it makes sense to put a little thought into where you're going to put them. As a general rule, you should put the walkway where people are going to walk.

A few years ago (2008), the University of Toronto spent a million dollars on constructing new pathways throughout the downtown campus. The new paths mostly followed the old paths but there were places where that didn't make sense. As I reported back then [If you build it, will they follow?], the old path didn't line up with the new ramp to my building (see photo below). The guys building the path agreed with me that the placement of the walkway made no sense but they were overruled by their supervisor who insisted that the alignment wasn't a problem. People would stay on the new walkway and they would be encouraged to do so by strategic placement of a big rock.



Can you guess what happened? That ramp is now the main entrance to my building for people coming up from the subway exit. Will they follow the path, taking a sharp right turn then a sharp left turn or will they cut straight across the grass making as much of a mess as before the new walkway was constructed?

Here's the result ...


Isn't that ridiculous? Just as predicted, people take the shortest distance between two points and if that means walking over the grass and making an ugly mess, then so be it. What's the point of spending a ton of money to make the campus look nice if this is the result?


Monday, July 15, 2013

Evidence for Intelligent Design

Remember how the IDiots are always trying to tell us that their movement is scientific? It's all about scientific evidence for design.

The facts say otherwise. Almost all of their arguments are based on "evidence" against evolution and on trashing scientists, especially Darwin. Much of their opposition has nothing to do with scientific evidence of design; instead, it's directed at materialism and atheism and other views that they see as an integral part of something called "Darwinism."

Let's see how bizarre this can get. Friedrich Nietzsche ("God is dead") is hardly someone who the IDiots respect for his philosophical view. But that doesn't matter as long as he said something bad about Charles Darwin [Nietzsche, possibly the Nazis’ favourite well-known philosopher, criticized Darwinism on aesthetic grounds].

But, wait a minute. If Nietzsche was a favorite of the Nazis then Darwin must have been opposed to Nazism because Nazi Neitsche criticized natural selection. I'm confused. What does this have to do with evidence of design?


How the IDiots View Genome Research

It's safe to say that a majority of knowledgeable scientists now agree that the most of our genome is junk. This is bad news for Intelligent Design Creationism because they have staked their credibility on the idea that if the DNA is present is must be the product of god(s) the intelligent designer and it must be there for a reason.

One of the latest posts on Evolution News & Views (sic) emphasizes this point [More Clues that Intergenic DNA Is Functional]. Its author doesn't identify herself/himself. The point of the post is to cherry-pick a couple of papers from the scientific literature, including the horrible paper by Hangauer et al. (2013) [see How to Make a Scientific Argument ].

Jenny McCarthy Will Be the New Co-Host of The View

You all remember Jenny McCarthy, right? She's the person who urges parents not to vaccinate their children, prompting formation of the Jenny McCarthy body count.

Sandwalk readers might recall that Jenny McCarthy was scheduled to appear at an Ottawa fund raising event last February until CFI Canada and the Ottawa Skeptics forced the organizers to dump her [Jenny McCarthy Dumped].

Now she's been officially named co-host of The View. What in the world was ABC thinking?

I have sent a complaint to ABC. Here's a convenient webpage: contact us.


Hat Tip: Friendly Atheist.

Monday's Molecule #209

Last week's molecule was depicted on a stamp honoring Gerty Cori. It was supposed to be the "Cori ester" (glucose 1-phosphate) but the image shown on the stamp is not correct. Nobody recognized that so there was no winner last week [Monday's Molecule #208].

Today's molecule is a very famous RNA with secondary structure. Do you recognize it without BLASTing the sequence?

Email your answers to me at: Monday's Molecule #209. I'll hold off posting your answers for 24 hours. The first one with the correct answer wins. I will only post 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.)

Sunday, July 14, 2013

Happy Bastille Day!

On July 14, 1789 a bunch of French citizens stormed the Bastille and liberated a handful of political prisoners [Bastille Day]. It marks the beginning of the French Revolution.

One of Ms. Sandwalk's ancestors is William Playfair, inventor of pie charts and histograms [Bar Graphs, Pie Charts, and Darwin]. He's famous because he knew Erasmus Darwin. He's also famous because there are stories that he took part in the Storming of the Bastille while living in Paris.

One the other hand, there are plenty of things for which he is less than famous [William Playfair] and there's a a good reason why his children left England and migrated to Canada becoming farmers near Perth, Ontario.


People I Met in Chicago at SMBE2013

I had a great time at SMBE2013 (Society for Molecular Biology and Evolution) in Chicago. Here are some of the people I met. I apologize for not including everyone—I forgot to take pictures of everyone I talked to.

I went to hear Masatoshi Nei give a talk on Monday morning (July 8) during a special session on "Ideas and Thoughts." The title of his talk was "Darwinism and the Theory of Mutation-Driven Evolution." This was the first time I had seen Nei in person and it was quite a thrill. I've been a huge fan ever since I read Molecular Evolutionary Genetics in 1987. That's when I first became aware of the power of population genetics and the importance of mutation and mutationism.

What Did Dan Graur Say in Chicago?

Dan Graur gave a fantastic and entertaining talk at SMBE2013 [Powerpoint]. He covered a lot of bases, but unfortunately left some out 'cause he had many slides that he didn't get to because of time limitations. Most of the audience enjoyed the talk very much—there was much laughter and enthusiastic head nodding. (I figure that two thirds of the audience agreed with his stance on junk DNA and ENCODE.)

Apparently Cornelius Hunter was in the audience because he blogged about it on Darwin's God: Dan Graur Gave a Great Talk This Week (copied on Uncommon Descent: Dan Graur Gave a Great Talk This Week). It's a shame he didn't make himself known to me or Reed Cartwright or Nick Matzke.

One of the things that Graur said was that if ENCODE is right then evolution is wrong. Now this may be a bit of an exaggeration, but not by much. If the ENCODE leaders are right that 85% of our genome has a biological function then we really do have to rethink the C-value paradox and genetic load. We also have to re-think a lot of biochemistry. I think that's what Dan meant. Cornelius Hunter says that's the one "glaring error" in Graur's presentation.

Theme

Genomes
& Junk DNA
Graur said that junk DNA is a "known known" and by that he means that there's plenty of evidence for junk DNA. It's not "dark matter" and we don't use the term "junk" to mask our ignorance. Speaking of ignorance, Cornelius Hunter seems to be completely unaware of any evidence for junk DNA. I guess he didn't stay to hear my presentation.


How Not to Do Science

Theme
Genomes
& Junk DNA
Many reputable scientists are convinced that most of our genome is junk. However, there are still a few holdouts and one of the most prominent is John Mattick. He believes that most of our genome is made up of thousand of genes for regulatory noncoding RNA. These RNAs (about 100 of them for every single protein-coding gene) are mostly involved in subtle controls of the levels of protein in human cells. (I'm not making this up. See: John Mattick on the Importance of Non-coding RNA )

It was a reasonable hypothesis at one point in time.

How do you evaluate a hypothesis in science? Well, one of the things you should always try to do is falsify your hypothesis. Let's see how that works ...
  1. The RNAs should be conserved. FALSE
  2. The RNAs should be abundant (>1 copy per cell). FALSE
  3. There should be dozens of well-studied specific examples. FALSE
  4. The hypothesis should account for variations in genome size. FALSE
  5. The hypothesis should be consistent with other data, such as that on genetic load. FALSE
  6. The hypothesis should be consistent with what we already know about the regulation of gene expression. FALSE
  7. You should be able to refute existing hypotheses, such as transcription errors. FALSE
Normally, you would abandon a hypothesis that had such a bad track record but true believers aren't about to do that. So what's next? Maybe these regulatory RNAs don't show sequence conservation but maybe their secondary structures are conserved. In other words, these RNAs originated as functional RNAs with a secondary structure but over the course of time all traces of sequence conservation have been lost and only the "conserved" secondary structure remains.1 The Mattick lab looked at the "conservation" of secondary structure as an indicator of function using the latest algorithms (Smith et al., 2013). Here's how they describe their attempts to prove their hypothesis in light of conflicting data ...
The majority of the human genome is dynamically transcribed into RNA, most of which does not code for proteins (1–4). The once common presumption that most non–protein-coding sequences are nonfunctional for the organism is being adjusted to the increasing evidence that noncoding RNAs (ncRNAs) represent a previously unappreciated layer of gene expression essential for the epigenetic regulation of differentiation and development (5–8). Yet despite an exponential accumulation of transcriptomic data and the recent dissemination of genome-wide data from the ENCODE consortium (9), limited functional data have fuelled discourse on the amount of functionally pertinent genomic sequence in higher eukaryotes (1, 10–12). What is incontrovertible, however, is that evolutionary conservation of structural components over an adequate evolutionary distance is a direct property of purifying (negative) selection and, consequently, a sufficient indicator of biological function The majority of studies investigating the prevalence of purifying selection in mammalian genomes are predicated on measuring nucleotide substitution rates, which are then rated against a statistical threshold trained from a set of genomic loci arguably qualified as neutrally evolving (13, 14). Conversely, lack of conservation does not impute lack of function, as variation underlies natural selection. Given that the molecular function of ncRNA may at least be partially conveyed through secondary or tertiary structures, mining evolutionary data for evidence of such features promises to increase the resolution of functional genomic annotations.
Here's what they found ..
When applied to consistency-based multiple genome alignments of 35 mammals, our approach confidently identifies >4 million evolutionarily constrained RNA structures using a conservative sensitivity threshold that entails historically low false discovery rates for such analyses (5–22%). These predictions comprise 13.6% of the human genome, 88% of which fall outside any known sequence-constrained element, suggesting that a large proportion of the mammalian genome is functional.
Apparently 13.6% of the human genome is a "large proportion." Taken at face value, however, the Mattick lab has now shown that the vast majority of transcribed sequences don't show any of the characteristics of functional RNA, including conservation of secondary structure. Of course, that's not the conclusion they emphasize in their paper.

Why not?

1. I can't imagine how this would happen, can you? You'd almost have to have selection AGAINST sequence conservation.

Smith, M.A., Gese, T., Stadler, P.F. and Mattick, J.S. (2013) Widespread purifying selection on RNA structure in mammals. Nucleic Acid Research advance access July 11, 2013 [doi: 10.1093/nar/gkt596]