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Thursday, September 05, 2013

The Purpose of the United Nations

After two devastating world wars, the nations of the world got together in San Francisco in 1945 to form the United Nations. The goal was to prevent further wars by pledging to resolve conflicts peaceably or, if that were not possible, to act collectively to reign in rogue nations. The fundamental idea was that no one nation could decide on its own to act as judge, jury, and executioner when it comes to making war. This applies especially to powerful nations whose self righteous attitudes often led them to believe that they could ignore the views of other nations.

The goals of the United Nations have not always been achieved. We have plenty of examples of nations acting unilaterally by going to war and many examples of groups of nations that ignored the United Nations. In spite of these examples, most nations still profess allegiance to the principles that led to the founding of the United nations.

Here's Chapter 1 of the Charter of the United Nations.
Article 1

The Purposes of the United Nations are:
  1. To maintain international peace and security, and to that end: to take effective collective measures for the prevention and removal of threats to the peace, and for the suppression of acts of aggression or other breaches of the peace, and to bring about by peaceful means, and in conformity with the principles of justice and international law, adjustment or settlement of international disputes or situations which might lead to a breach of the peace;
  2. To develop friendly relations among nations based on respect for the principle of equal rights and self-determination of peoples, and to take other appropriate measures to strengthen universal peace;
  3. To achieve international co-operation in solving international problems of an economic, social, cultural, or humanitarian character, and in promoting and encouraging respect for human rights and for fundamental freedoms for all without distinction as to race, sex, language, or religion; and
  4. To be a centre for harmonizing the actions of nations in the attainment of these common ends.
Article 2

The Organization and its Members, in pursuit of the Purposes stated in Article 1, shall act in accordance with the following Principles.
  1. The Organization is based on the principle of the sovereign equality of all its Members.
  2. All Members, in order to ensure to all of them the rights and benefits resulting from membership, shall fulfill in good faith the obligations assumed by them in accordance with the present Charter.
  3. All Members shall settle their international disputes by peaceful means in such a manner that international peace and security, and justice, are not endangered.
  4. All Members shall refrain in their international relations from the threat or use of force against the territorial integrity or political independence of any state, or in any other manner inconsistent with the Purposes of the United Nations.
  5. All Members shall give the United Nations every assistance in any action it takes in accordance with the present Charter, and shall refrain from giving assistance to any state against which the United Nations is taking preventive or enforcement action.
  6. The Organization shall ensure that states which are not Members of the United Nations act in accordance with these Principles so far as may be necessary for the maintenance of international peace and security.
  7. Nothing contained in the present Charter shall authorize the United Nations to intervene in matters which are essentially within the domestic jurisdiction of any state or shall require the Members to submit such matters to settlement under the present Charter; but this principle shall not prejudice the application of enforcement measures under Chapter Vll.
Today we are dealing with the possibility that the most powerful nation in the world will attack a much weaker nation in spite of the opposition of many other nations, especially important permanent members of the Security Council. No peaceful resolutions are being explored and very few politicians in that powerful nation are expressing concern that they are ignoring the United Nations. All the rhetoric from that nation seems to be based on the idea that their leaders are judge, jury, and executioner when it comes to policing weaker, more vulnerable, nations. Most of those politicians do not see a problem with bombing another nation in order to punish it for a wrongdoing. Violence and war are viable options and, in this case, the first choice.

To those of us who live in other countries, that is not the kind of behavior one would like to see in the most powerful nation in the world.

I think it's about time that the United States of American quit the United Nations since it clearly has no intention of living up to its commitment to peaceful resolution of conflicts and collective action in cooperation with other nations.


Wednesday, September 04, 2013

Carnival of Evolution #63

The latest issue of Carnival of Evolution is hosted by Adam Benton, an undergraduate at the University of Liverpool. He's studying evolutionary anthropology. Adam blogs at Evoanth. Read: Carnival of Evolution: Eclectic September edition.
Step right up ladies and gentlemen, here for one month only under the big top is the one, the only, the carnival of evolution. For your delectable delight we have a range of articles, covering everything from bacterial evolution to Neanderthal hearing to T. rex‘s eating habits.

As someone who spends a lot of time focusing on human evolution it can be rather easy to get tunnel vision and miss all of this excellent writing on non-evoanth subjects. I’ve thoroughly enjoyed being given a taste of the world outside my field. I only wish there were some way to get people to send me these stories every month.

But before I start trying to contract out my science reading, I better get round to the reason we’re all here. So without much further ado: Welcome to the September edition of the Carnival of Evolution!
This month's edition highlights the people who SUBMITTED articles as opposed to those who wrote them. This is a reminder that anyone can submit at article—it's not just authors who submit their own works.

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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Join the University of Toronto Secular Alliance (UTSA)

This is Orientation Week at the University of Toronto. There are 10,000 beginning first year students who are just leaning what they got themselves into. Classes start next week.

Today is "Clubs Day." It's the day when all the clubs set up booths around Hart House Circle and the students come to sign up for various activities. That's Cameron Proctor, the Vice President of the University of Toronto Secular Alliance [Facebook] at his booth. I saw his list—there were about 50 people signed up. I had to clear away a huge crowd in order to get the picture.

I didn't count the number of religious clubs but there must have been at least a dozen. Each one had five or six people soliciting new members and each one had more inquisitive students at the tables than UTSA. I don't get it. I figure that half the students are nonblievers but I guess they aren't interested in a club for nonbelievers.

UTSA has a number of programs planned for this Fall and the members meet every second Thursday starting Sept. 28. Maybe I'll see you there?




Monday's Molecule #213

Last week's molecule was 6-phosphogluconolactone, the first intermediate in the pentose phosphate pathway. The winner was Brian Shewchuck [Monday's Molecule #212].

Today (Wednesday, but who's counting?) we're going to continue with basic metabolism in honor of all students who are just being introduced to the wonders of introductory biochemistry. Give the common name and identify the pathway. Explain briefly why this pathway is important.

Email your answers to me at: Monday's Molecule #213. I'll hold off posting your answers for 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.)

James Hood (1776-1859)

We were at a wedding in Orillia (Ontario) on the weekend with my son and his wife. On the way home we took the long route and stopped at the Creemore Union Cemetery in Creemore, Ontario. The town is known mainly for its beer (Creemore Springs Brewery) but we were looking for ancestors.

James Hood was born on April 6, 1775 in Kelso, Scotland but his family moved to the Glascow area a few years later. His father was a Calton weaver and so was James. The recession following the end of the Napoleonic Wars meant that the weavers could no longer make a decent living and the British government encouraged them to emigrate to Canada by offering free passage and free land.

James and his family arrived in Canada on the "Prompt" in 1820. They settled originally in the area around Perth, Ontario. My wife, Leslie (neé Rodger) descends from James' son William whose family remained in Perth. James Hood and many of his other children moved to the Creemore area in 1830 and that's where he died on July 30, 1859.

James Hood is my wife's great, great, great, great, grandfather (and the great5 grandfather of Gordon and Jane). He is also the great, great, great grandfather of Mitt Romney [see A Mormon Tale].


Thursday, August 29, 2013

Richard Lenski's Classic Papers: Luria and Delbrück, 1943

Richard Lenski has joined a number of other biologists and blogged about classic "must-read" papers. His first example is Luria and Delbrück (1943)—the Fluctuation Test. It's an excellent description and there's a personal touch.

John Dennehy [The Fluctuation Test and Jonathan Eisen [Luria and Delbrück] also picked the same paper. That means it must really be a "must-read"! (I agree.)

Given that the early history of molecular biology is no longer being taught, I imagine that there are quite a few of you who have never heard of Max Delbrück (1906-1981) or Salvador Luria (1912-1991) in spite of the fact they are Nobel prize winners. Here's some of my posts on them ....

The Velvet Underground of Molecular Biology
Nobel Laureates Max Delbrück, Alfred D. Hershey, Salvador E. Luria


Core Misconcept: Epigenetics

Sarah C.P. Williams is a science writer. She published an article in PNAS last February: Epigenetics. Here's the opening paragraphs ...
Despite the fact that every cell in a human body contains the same genetic material, not every cell looks or behaves the same. Long nerve cells stretch out the entire length of an arm or a leg; cells in the retina of the eye can sense light; immune cells patrol the body for invaders to destroy. How does each cell retain its unique properties when, in its DNA-containing nucleus, it has the same master set of genes as every other cell? The answer is in the epigenetic regulation of the genes: the control system that dictates which of many genes a cell uses and which it ignores. The same mechanism could also explain why identical twins—who have identical genes—can develop different diseases, traits, or personalities.

Epigenetic regulation consists of chemical flags, or markers, on genes that are copied along with the genes when the DNA is replicated. Without altering the sequence of DNA’s molecular building blocks, epigenetic changes can alter the way a cell interacts with DNA. These changes can block a cell’s access to a gene, turning it off for good.
Statements like that make me cringe. Not only is she ignoring decades of work on the real explanation of differential gene expression, she is also proposing an explanation that can't possibly live up to the claim she is making.

PNAS should be embarrassed.

Fortunately, I'm not the only one who was upset. Mark Ptashne had the same reaction as several hundred other scientists but he took the time to write up his objections and get them published in the April issue of PNAS [Epigenetics: Core Misconcept]. I'll quote his opening paragraph and then let you follow the link and get educated about real science.
Indeed understanding this problem has been an overarching goal of research in molecular, developmental, and, increasingly, evolutionary biology. And over the past 50 years a compelling answer has emerged from studies in a wide array of organisms. Curiously, the article ignores this body of knowledge, and substitutes for it misguided musings presented as facts.
There was a time when every molecular biology student knew how gene expression was controlled. They knew about the pioneering work in bacteria and 'phage and the exquisite details that were worked out in the '60s, '70s, and '80s. That information has been lost in recent generations. Our current crop of graduate students couldn't tell you how gene expression is controlled in bacteriophage λ.

If you are one of those students then I urge you to read Ptashne's book A Genetic Switch before it goes out of print. If the current trends continue, that information is soon going to pass out of the collective memory of molecular biologists just as it has been forgotten (or never learned) by science writers.


What Happens When a Creationist Argument Is Refuted?

A few days ago, Jonathan McLatchie published an article on evolution News & Views (sic) where he claimed that humans embryos synthesize the enzyme that makes vitamin C [A Simple Proposed Model For Function of the Human Vitamin C GULO Pseudogene]. This is important for creationists because the gene for that enzyme is a classic pseudogene—a formerly active gene that has lost it's function.

Intelligent Design Creationists don't like pseudogenes because they are junk and their intelligent designer would not fill up the human genome with junk. Hence, pseudogenes must have some function that has yet to be discovered.

Wednesday, August 28, 2013

An Example of a Very Bad Press Release

Cornelius Hunter is gloating over another study that disputes the notion of junk DNA [More Functions For “Junk” DNA, and More Functions For “Junk” DNA]. His article sounded interesting so I followed the link to the press release.

There was something about the press release that sounded suspicious and that prompted me to seek out the original published paper. Here it is with the abstract ...
Wong, J.J.-L., Ritchie, W., Ebner, O.A., Selbach, M., Wong, J.W., Huang, Y., Gao, D., Pinello, N., Gonzalez, M. and Baidya, K. (2013) Orchestrated Intron Retention Regulates Normal Granulocyte Differentiation. Cell 154:583-595. [PDF] [doi: 10.1016/j.cell.2013.06.052]

Intron retention (IR) is widely recognized as a consequence of mis-splicing that leads to failed excision of intronic sequences from pre-messenger RNAs. Our bioinformatic analyses of transcriptomic and proteomic data of normal white blood cell differentiation reveal IR as a physiological mechanism of gene expression control. IR regulates the expression of 86 functionally related genes, including those that determine the nuclear shape that is unique to granulocytes. Retention of introns in specific genes is associated with downregulation of splicing factors and higher GC content. IR, conserved between human and mouse, led to reduced mRNA and protein levels by triggering the nonsense-mediated decay (NMD) pathway. In contrast to the prevalent view that NMD is limited to mRNAs encoding aberrant proteins, our data establish that IR coupled with NMD is a conserved mechanism in normal granulopoiesis. Physiological IR may provide an energetically favorable level of dynamic gene expression control prior to sustained gene translation.
The authors found 86 genes expressed in mouse granulocytes where there were at least some transcripts that retained an intron. This could be due to mistakes in splicing but the authors prefer to think that intron retention is part of a regulatory step. The transcripts that retain an intron are degraded and this reduces the level of protein that would have been made if a properly spliced transcript had produced a functional mRNA.

It's an example of down-regulation, according to the authors. In most cases the intron-retaining transcripts make up only a few percent of the total transcripts but this is presumably enough to make a difference. In 25 of the genes, the aberrant transcripts are more that 25% of the total cytoplasmic transcripts.

There's nothing in the paper that mentions junk DNA.

Contrast this with the press release from Centenary Institute, Sydney Australia. I reproduce it below ...
How 'Junk DNA' Can Control Cell Development

Aug. 2, 2013 — Researchers from the Gene and Stem Cell Therapy Program at Sydney's Centenary Institute have confirmed that, far from being "junk," the 97 per cent of human DNA that does not encode instructions for making proteins can play a significant role in controlling cell development.

And in doing so, the researchers have unravelled a previously unknown mechanism for regulating the activity of genes, increasing our understanding of the way cells develop and opening the way to new possibilities for therapy.

Using the latest gene sequencing techniques and sophisticated computer analysis, a research group led by Professor John Rasko AO and including Centenary's Head of Bioinformatics, Dr William Ritchie, has shown how particular white blood cells use non-coding DNA to regulate the activity of a group of genes that determines their shape and function. The work is published today in the scientific journal Cell.

"This discovery, involving what was previously referred to as "junk," opens up a new level of gene expression control that could also play a role in the development of many other tissue types," Rasko says. "Our observations were quite surprising and they open entirely new avenues for potential treatments in diverse diseases including cancers and leukemias."

The researchers reached their conclusions through studying introns -- non-coding sequences which are located inside genes.

As part of the normal process of generating proteins from DNA, the code for constructing a particular protein is printed off as a strip of genetic material known as messenger RNA (mRNA). It is this strip of mRNA which carries the instructions for making the protein from the gene in the nucleus to the protein factories or ribosomes in the body of the cell.

But these mRNA strips need to be processed before they can be used as protein blueprints. Typically, any non-coding introns must be cut out to produce the final sequence for a functional protein. Many of the introns also include a short sequence -- known as the stop codon -- which, if left in, stops protein construction altogether. Retention of the intron can also stimulate a cellular mechanism which breaks up the mRNA containing it.

Dr Ritchie was able to develop a computer program to sort out mRNA strips retaining introns from those which did not. Using this technique the lead molecular biologist of the team, Dr Justin Wong, found that mRNA strips from many dozens of genes involved in white blood cell function were prone to intron retention and consequent break down. This was related to the levels of the enzymes needed to chop out the intron. Unless the intron is excised, functional protein products are never produced from these genes. Dr Jeff Holst in the team went a step further to show how this mechanism works in living bone marrow.

So the researchers propose intron retention as an efficient means of controlling the activity of many genes. "In fact, it takes less energy to break up strips of mRNA, than to control gene activity in other ways," says Rasko. "This may well be a previously-overlooked general mechanism for gene regulation with implications for disease causation and possible therapies in the future."
The published paper has nothing to do with junk DNA. Even if intron retention were a common mechanism of gene regulation (it is not), that would only account for about 100 base pairs per gene of additional sequence-dependant information. That's less than 0.1% of the genome.

This is a bad press release because it highlights information that is not in the published paper. The authors bear responsibility for press releases from their own institute that distort their published work. While they may not have written the press release, they presumably are quoted correctly and they should be aware of what's in the press release.

I wonder if they are willing to defend this press release as an accurate representation of their published work?


Saturday, August 24, 2013

John Mattick vs. Jonathan Wells

John Mattick and Jonathan Wells both believe that most of the DNA in our genome is functional. They do not believe that most of it is junk.

John Mattick and Jonathan Wells use the same arguments in defense of their position and they quote one another. Both of them misrepresent the history of the junk DNA debate and both of them use an incorrect version of the Central Dogma of Molecular Biology to make a case for the stupidity of scientists. Neither of them understand the basic biochemistry of DNA binding proteins leading them to misinterpret low level transcription as functional. Jonathan Wells and John Mattick ignore much of the scientific evidence in favor of junk DNA. They don't understand the significance of the so-called "C-Value Paradox" and they don't understand genetic load. Both of them claim that junk DNA is based on ignorance.

Friday, August 23, 2013

Reading the Entrails of Chickens

Dan Graur has a recent post on the phylogeny of placental mammals [The Root of the Placental Phylogenetic Tree: Are we Overlooking Something?]. He refers to a recent review in Molecular Biology and Evolution (MBE) that discusses various options. Graur believes that the question has been settled by examining transposon insertions.

But that's not the part that caught my attention. At the end of his post he says,
Finally, there is a small sentence in the Teeling and Hedges commentary that drove me up the wall: “The timing of the splitting event—approximately 100 Ma based on molecular clocks—is not in debate, at least among molecular evolutionists (Hedges et al. 1996…” Actually, dear Blair, it is. And whether you like it or not, both William Martin and I are fine molecular evolutionists.
The reference is to a paper by Dan Graur and Bill Martin—a formidable team that you want on your side because the alternative can be very embarrassing. You really, really don't want to mess with these guys.

We need more papers like this one.

Graur, D. & Martin, W. (2004) Reading the entrails of chickens: molecular timescales of evolution and the illusion of precision. TRENDS in Genetics 20:80-86 [doi: 10.1016/j.tig.2003.12.003] [PDF]

How IDiots Would Activate the GULOP Pseudogene

The enzyme L-glucono-γ-lactone oxidase is required for the synthesis of vitamin C. Humans cannot make this enzyme because the gene for this enzyme is defective [see Human GULOP Pseudogene]. The GenBank entry for this pseudogene is GeneID=2989. GULOP is located on chromosome 8 at p21.1 in a region that is rich in genes.

Here's a diagram that compares what is left of the human GULOP pseudogene with the functional gene in the rat genome.

Best Beatles' Songs

Jerry Coyne thinks that the Beatles are the greatest rock group ever [Match this song!]. I'm pleased to announce that I agree with him on this point.

Jerry thinks that A Day in the Life is the best Beatles' song and that's where we part company. His second choice is Eleanor Rigby [Eleanor Rigby] and that's also one of my top ten.

We'll see what his other favorites are over the next few days. If he doesn't mention the very best song (IMHO) I'll correct him when he's finished.


Some Questions for IDiots

Here's a short quiz for proponents of Intelligent Design Creationism. Let's see if you have been paying attention to real science. Please try to answer the questions below. Supporters of evolution should refrain from answering for a few days in order to give the creationists a chance to demonstrate their knowledge of biology and of evolution.

The bloggers at Evolution News & Views (sic) are promoting another creationist book [see Biological Information]. This time it's a collection of papers from a gathering of creationists held in 2011. The title of the book, Biological Information: New Perspectives suggests that these creationists have learned something new about biochemistry and molecular biology.

One of the papers is by Jonathan Wells: Not Junk After All: Non-Protein-Coding DNA Carries Extensive Biological Information. Here's part of the opening paragraphs.
James Watson and Francis Crick’s 1953 discovery that DNA consists of two complementary strands suggested a possible copying mechanism for Mendel’s genes [1,2]. In 1958, Crick argued that “the main function of the genetic material” is to control the synthesis of proteins. According to the “ Sequence Hypothesis,” Crick wrote that the specificity of a segment of DNA “is expressed solely by the sequence of bases,” and “this sequence is a (simple) code for the amino acid sequence of a particular protein.” Crick further proposed that DNA controls protein synthesis through the intermediary of RNA, arguing that “the transfer of information from nucleic acid to nucleic acid, or from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid, is impossible.” Under some circumstances RNA might transfer sequence information to DNA, but the order of causation is normally “DNA makes RNA makes protein.” Crick called this the “ Central Dogma” of molecular biology [3], and it is sometimes stated more generally as “DNA makes RNA makes protein makes us.”

The Sequence Hypothesis and the Central Dogma imply that only protein-coding DNA matters to the organism. Yet by 1970 biologists already knew that much of our DNA does not code for proteins. In fact, less than 2% of human DNA is protein-coding. Although some people suggested that non-protein-coding DNA might help to regulate gene expression, the dominant view was that non-protein-coding regions had no function. In 1972, biologist Susumu Ohno published an article wondering why there is “so much ‘ junk’ DNA in our genome” [4].
  1. Crick published a Nature paper on The Central Dogma of Molecular Biology in 1970. Did he and most other molecular biologists actually believe that "only protein-coding DNA matters to the organism?"
  2. Did Crick really say that "DNA makes RNA makes protein" is the Central Dogma or did he say that this was the Sequence Hypothesis? Read the paper to get the answer—the link is below).
  3. Is it true that, in 1970, the majority of molecular biologists did not believe in repressor and activator binding sites (regulatory DNA)?
  4. Is it true that in 1970 molecular biologists knew nothing about the functional importance of non-transcribed DNA sequences such as centromeres and origins of DNA replication?
  5. It is true that most molecular biologists in 1970 had never heard of genes for ribosomal RNAs and tRNAs (non-protein-coding genes)?
  6. If the answer to any of those questions contradicts what Jonathan Wells is saying then why do you suppose he said it?

Crick, F. (1970) Central Dogma of Molecular Biology. Nature 227:561-563. [PDF]

Wednesday, August 21, 2013

Goodbye Copenhagen

We've been in Copenhagen for a few days but today is the last day of our vacation. We fly to Iceland and Toronto in a few hours.