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.



Sunday, August 18, 2013

Saint Petersburg

Here are some photos of Saint Petersburg. I was happy to visit the cruiser Aurora in the Neva river. I first read about its role in the Russian revolution when I was in high school.

The fourth photo shows a typical street scene in the city. You should be able to translate the sign (СТОП) under the stop lights if you were paying attention to my post from a few weeks ago.


Saint Petersburg: Hermitage Museum

The highlight of our Baltic cruise was the visit to Saint Petersburg, Russia. We hired a guide and driver to take us around to the various sites in Saint Petersburg and the outskirts. The Hermitage (Зрмитаж) museum is located on the banks of one of the main channels of the Neva river (Болъшая Нева). The first photo shows a view form across the river.

This is the old winter palace of the Russian Czars so the building itself is part of the history—like the Louvre in Paris.

The second photo is one of the spectacular views from inside the museum. Everyone says that you really need three days to see everything and I agree. However, our guide took us on a brief tour of the major highlights so we got a good impression in just three hours.

The last photo shows us getting into our van at the end of the visit. If you look closely, you’ll see the name of Ms. Sandwalk’s blog on the dashboard (click to embiggen).



A Rainy Day in Helsinki

We visited Helsinki, Finland, a few days ago (August 14, 2013). It was a rainy day. We spent most of our time shopping and walking around the old town.


Wednesday, August 14, 2013

Stockholm: Old Town

We visited Stockholm yesterday and toured the city with my cousin Sharon and her husband Dennis. (That’s them with Ms. Sandwalk in the third photo.) Here are some photos of the Old Town including one of the Swedish Academy where I tried to put in a good word for all my readers.


45 Years Ago

We're celebrating our 45th wedding anniversary by taking a cruise in the Baltic. We were in Oslo, Norway on our anniversary day (August 9) where we met our friends Dag and Robin from graduate student days. They are als0 marride 45 years so we celebrated with champagne at their house. More about that later.




Monday, August 12, 2013

University of Rostock

The University of Rostock was founded in 1419. It’s said to be the oldest university in the Baltic Sea area. The main university building is a prominent landmark in Rostock but I was more interested in the Zoology building off to the side.

Looks like I just missed an important conference. Does everyone know who Willi Hennig is?



Warnemünde and Rostock

Yesterday our boat stopped at the habor in Warnemünde, Germany. There was a lot of activity of the quay in Warnemünde because a number of tall ships were in the harbor.

We took the train to the medieval town of Rostock—a key port in the Hansiatic League (Hansa=guilds). The architecture was similar to that in other leading cities of the Hansiatic League, notably Bruges.



Sunday, August 11, 2013

Cruising

We've been on this boat for three days and we'll be on it for another 8 days as we cruise the Baltic Sea. Internet access costs 70 cents ($0.75 US) per minute so posts will be short and infrequent.




Wednesday, August 07, 2013

Carnival of Evolution #62: The Whig History

The latest issue of Carnival of Evolution is hosted by Joachim D, an evolutionary ecologist who blogs at Ecology and Evolution Footnotes. Read: Carnival of Evolution 62: The Whig History .
When it comes to the history of evolutionary theory, a whiggish image could look something like [the figure below]

I leave it to the readers to come up with a female version (including, for example, Maria Sibylla Merian, Rosalind Franklin, Barbara McClintock, Christiane Nüsslein-Volhard).

Arranging July's posts that I found interesting or entertaining as well as the few submitted by others according to a Whig history of evolutionary theory in the following is purely ornamental and does, of course, not imply any whiggishness on the side of the contributors.


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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Tuesday, August 06, 2013

Carnival of Evolution #61: Crustie Lovin; Edition

I was out of town when the last two Carnivals of Evolution were published so I'm doing a bit of catchup. The July issue of Carnival of Evolution was hosted by Marc Srour at Teaching Biology. He's the only blogger I know who is based in Cyprus. (He may have just moved to Japan.) Read: Carnival of Evolution #61: Crustie Lovin; Edition.
Hello, and welcome to the Carnival of Evolution #61. For this edition, I’ve chosen to celebrate what I perceive as an inexplicably underappreciated group of animals: the Crustacea. Of the major arthropod groups, I notice that crustaceans often get the short end of the stick. Everyone can name insects and recognise spiders, but besides seafood, crustaceans seem to be a question mark with most people. Insects and spiders have movies and songs written about them; crabs are the logo for cancer, the vernacular name for an STD, and they are an astrological sign.

Insulting. Crustaceans are awesome. There may be over a million insect species, but crustaceans take the cake when it comes to disparity, or morphological diversity, a measure in which no other taxon can match them.

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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Monday, August 05, 2013

Carnival of Evolution #60: Party like it’s 1953

I was out of town when the last two Carnivals of Evolution were published so I'm doing a bit of catchup. The June issue of Carnival of Evolution was hosted by Zen Faulkes at NeuroDojo. He's a invertebrate neuroethologist, whatever that is. Read: Carnival of Evolution #60: Party like it’s 1953.
Ladies and gentlemen, this is a special edition of the Carnival of Evolution. It’s the big six oh!

In honor of that achievement, we shall share this carnival’s space with other events celebrating their sixtieth anniversary.


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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Monday's Molecule #212

Last week's molecule was a thymine dimer. The winners were Alex Ling and Matt McFarlane. [Monday's Molecule #211].

Today's molecule is an important part of a major pathway. Give the common name and identify the pathway. Explain briefly why this pathway is important.

Email your answers to me at: Monday's Molecule #212. 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.)

Sunday, August 04, 2013

Dear Denyse, Stop Digging

You're not going to believe what Denyse O'Leary just posted on Uncommon Descent: Junk DNA: Just because information is never used, doesn’t mean it is junk.
Further to Cornelius Hunter’s “Evolutionist: We do not promote any ‘spiritual ideologies,’” (in which he recounts that recent findings about RNA structure conservation suggest that even more of the mammalian genome is functional than supposed, hence there is less “junk DNA”:

I’ve never clearly understood Darwin’s fans attachment to junk DNA. It makes a good “anti-God” statement, as long as you are certain that the stuff is not and never could be any use. But that is precisely what is now widely contested. And it was a trap they need not have fallen into.

But a simple illustration will show that even if most of the information in DNA were never used, it would still be valuable. Let us say I have a directory of members of a club I belong to. I never use most of the phone numbers. Many numbers may never be used by anyone.

Does lack of use make that proportion of the directory junk?