Last week's molecule (right) [Monday's Molecule #239] was 2-carboxy-D-arabinitol 1-phosphate. It's an inhibitor of the enzyme ribulose 1,5-bisphosphate carboxylase-oxygenase, better known as Rubisco. That's the key enzyme responsible for CO2 fixation in the Calvin cycle. Plants have to inhibit Rubisco during the night when the lack of sunlight prevents production of ATP and NADPH by photosynthesis. One of the ways they inhibit the enzyme is to produce 2-carboxy-D-arabinitol 1-phosphate at night. The winner is Piotr Gąsiorowski.
This week's molecule (below) is pretty complicated. I don't expect a complete name; just concentrate on getting the correct name of the core part of the molecule on the left. In addition to identifying the molecule, you need to explain what it is used for and, specifically, the purpose of the -N3 group in the lower left corner of the molecule.
Email your answer to me at: Monday's Molecule #239. The first one with the correct answer wins. I will only post the names of winners 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.)
Let's briefly review what happened in September 2012 when the ENCODE Consortium published their results (mostly in Nature).
Here's the abstract of the original paper published in Nature in September 2012 (Birney et al. 2012). Manolis Kellis (see below) is listed as a principle investigator and member of the steering committee.
The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research.
Most people reading this picked up on the idea that 80% of the genome had a function.
I draw your attention to a new paper on junk DNA by my friends Alex Palazzo and Ryan Gregory (Palazzo and Gregory, 2014).
You should read this paper if you want a nice summary of the evidence for a high percentage of junk in our genome. They cover genetic load, sequence conservation, and the evidence from the genome sequence itself. There's a brief description of the nearly-neutral theory of molecular evolution and why it's relevant to the debate.1
One of the most important contributions is an explanation of the C-Value Paradox and the Onion Test. The Onion Test was originally published on Ryan's blog (The onion test) but some people won't reference blog posts so here it is in a peer-reviewed paper.
There are several key points to be understood regarding genome size diversity among eukaryotes and its relationship to the concept of junk DNA. First, genome size varies enormously among species [18], [19]: at least 7,000-fold among animals and 350-fold even within vertebrates. Second, genome size varies independently of intuitive notions of organism complexity or presumed number of protein-coding genes (Figure 1). For example, a human genome contains eight times more DNA than that of a pufferfish but is 40 times smaller than that of a lungfish. Third, organisms that have very large genomes are not few in number or outliers—for example, of the >200 salamander genomes analyzed thus far, all are between four and 35 times larger than the human genome [18]. Fourth, even closely related species with very similar biological properties and the same ploidy level can differ significantly in genome size.
These observations pose an important challenge to any claim that most eukaryotic DNA is functional at the organism level. This logic is perhaps best illustrated by invoking “the onion test” [20]. The domestic onion, Allium cepa, is a diploid plant (2n = 16) with a haploid genome size of roughly 16 billion base pairs (16 Gbp), or about five times larger than humans. Although any number of species with large genomes could be chosen for such a comparison, the onion test simply asks: if most eukaryotic DNA is functional at the organism level, be it for gene regulation, protection against mutations, maintenance of chromosome structure, or any other such role, then why does an onion require five times more of it than a human? Importantly, the comparison is not restricted to onions versus humans. It could as easily be between pufferfish and lungfish, which differ by ~350-fold, or members of the genus Allium, which have more than a 4-fold range in genome size that is not the result of polyploidy [21].
In summary, the notion that the majority of eukaryotic noncoding DNA is functional is very difficult to reconcile with the massive diversity in genome size observed among species, including among some closely related taxa. The onion test is merely a restatement of this issue, which has been well known to genome biologists for many decades [18].
1. A little birdy tells me that there's a "better" paper coming out in a few months. 
Palazzo, A. and Gregory T.R. (2014) The Case for Junk DNA. PLoS Genetics (published May 8, 2014) [doi: 10.1371/journal.pgen.1004351]
I just discovered a new paper on the origin of life (Keller et al. 2014). The authors think they are looking at the first primitive biochemical pathways, which they identify as glycolysis and the pentose phosphate pathways.
Here's what they did. They took a bunch of pure sugar phosphates1 and dissolved them in water containing salts and metal ions that were likely present in the primordial oceans. They heated the solution up to 70° C and looked at the degradation products. Low and behold, the sugar phosphates degraded and sometime the products were other intermediates in the glycolytic and pentose phosphate pathway, including pyruvate and glucose.
They conclude that ...
According to Friendly Atheist, there's been a Supreme Court Disaster: In a 5-4 Ruling, Justices Approve of Christian Prayers in Greece, New York.
Apparently a majority of US Supreme Court justices think it's okay to say Christian prayers at the opening of a town council meeting. There seems to be widespread agreement among all justices that there's nothing wrong with prayers as long as the town makes an effort to be inclusive. The majority opinion was written by Justice Anthony Kennedy. He says that making the prayers "nonsectarian" would be equivalent to asking the politicians to "to act as supervisors and censors of religious speech."
He also says that as long as the town tries to accommodate all faiths there's nothing wrong with prayers, even if almost all the churches were Christian [TOWN OF GREECE, NEW YORK v. GALLOWAY ET AL.].
To hold that invocations must be nonsectarian would force the legislatures that sponsor prayers and the courts that are asked to decide these cases to act as supervisors and censors of religious speech, a rule that would involve government in religious matters to a far greater degree than is the case under the town’s current practice of neither editing or approving prayers in advance nor criticizing their content after the fact.
…
Finally, the Court disagrees with the view taken by the Court of Appeals that the town of Greece contravened the Establishment Clause by inviting a predominantly Christian set of ministers to lead the prayer. The town made reasonable efforts to identify all of the congregations located within its borders and represented that it would welcome a prayer by any minister or layman who wished to give one. That nearly all of the congregations in town turned out to be Christian does not reflect an aversion or bias on the part of town leaders against minority faiths. So long as the town maintains a policy of nondiscrimination, the Constitution does not require it to search beyond its borders for non-Christian prayer givers in an effort to achieve religious balancing.
Only one of the judges put her finger on the real issue. Justice Elena Kagan said,
When a person goes to court, a polling place, or an immigration proceeding — I could go on: to a zoning agency, a parole board hearing, or the DMV — government officials do not engage in sectarian worship, nor do they ask her to do likewise. They all participate in the business of government not as Christians, Jews, Muslims (and more), but only as Americans — none of them different from any other for that civic purpose. Why not, then, at a town meeting?
Exactly. Why is it necessary to have prayers at town meetings? Just drop them like most cities and towns in Ontario did when our Appeals Court ruled that they violated the Charter of Rights? [see Prayer at Mississauga City Council]
Many of the creationists are just learning about Neutral Theory for the first time in their lives. (The basics were published in the late 1960s—over 45 years ago.)
Vincent Torley (vjtorley), a philosopher from Australia, has struggled with the idea for several weeks and now he thinks he has some challenging questions for evolutionary biologists. Those creationists are really fast learners. It took me several years of study before I really grasped the basic concepts and the theory behind population genetics. Torley's questions are at: Will the real Neutral Theory please stand up?. The obligatory piling on by "News" is at: Is there a real neutral theory of evolution?.
Torley begins with ...
The Canadian Association of University Teachers (CAUT) has launched a campaign to alert the public about changes in science policy and funding. The Conservative government of Stephen Harper has shifted funds toward directed research and starved Canadian scientists who focus on basic, curiosity motivated, research.
What this means is that young scientists are finding it increasingly difficult to get funding from the government. It means that scientists in mid-career are losing their grants and this means that research technicians have to be fired, graduate students can't be funded, and post-docs have to find another position.
Why is this important? Why should you care? Those are the questions that CAUT wants to answer by sponsoring meetings across the nation to explain why it's important to "Get Science Right." Come to a Town Hall meeting at the University of Toronto (Toronto, Ontario, Canada) and learn more. The meeting starts at 7pm. It's in room 119 at Emmanuel College (Victoria Uiniversity). [Facebook: Get Science Right - Toronto Town Hall]
Let me know if you plan to attend. We could get together before or after the meeting.
Last week's molecules (right) [Monday's Molecule #238] were correctly identified by Dean Bruce (again) who wrote ...
... it is 3-hydroxy-3-methylglutarate-CoA (HMG-CoA) synthetase. HMG-CoA appears to be the only molecule in the active sites of the illustration. Acetoacetyl-CoA and Acetyl-CoA in a Claisen condensation (of the beta-carbonyl of acetoacetyl-CoA) form HMG-CoA.
The mitochondrial one is the isoform involved in metabolic pathology. The disease is called "mitochondrial HMG-CoA synthetase-2 deficiency" in the Online Mendelian Inheritance of Man.
This week's molecule is an important regulatory molecule in some species. Identify it using the standard IUPAC nomenclature and describe the enzyme whose activity it regulates.
Email your answer to me at: Monday's Molecule #239. The first one with the correct answer wins. I will only post the names of winners 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.)
There are many ways of defining the gene but only some of them are reasonable in the 20th and 21st centuries [What Is a Gene?]. By the 1980s most knowledgeable biologists were thinking of a gene as a DNA sequence that's transcribed to produce a functional product.
They were familiar with genes that encoded proteins and with a wide variety of genes that produce functional RNAs like ribosomal RNA , transfer RNA, regulatory RNAs, and various catalytic RNAs. It would have been difficult to find many knowledgeable biologists who thought that all genes encoded proteins.
By the 1980s, most knowledgeable biologists were aware of RNA processing. They knew that the primary transcripts of genes could be modified in various ways to produce the final functional form. They knew about alternative splicing. All these things were taught in undergraduate courses and written in the textbooks.
Here's how Michael White views that history in: Your Genes Are Obsolete.
Creationists in general, and Intelligent Design Creationists in particular, feel very threatened by the idea that most of our genome is junk. We know why they feel threatened: it's because a genome full of junk doesn't seem like something gods would design on purpose. It's pretty hard to reconcile junk DNA with with gods that spend so much effort designing bacterial flagella.
The creationists get very excited whenever a group of scientists publish evidence for function in junk DNA and they could hardly contain themselves when the ENCODE preliminary results were published in 2007 because the ENCODE Consortium said that most of the human genome was functional. You will recall that the creationists fell hook line and sinker for the ENCODE publicity hype in September 2012 when the ENCODE leaders came right out and said that their analysis of the entire genome shows there is almost no junk in the human genome.
The creationists, just like the ENCODE leaders, were very resistant to all of the scientific evidence for junk DNA. Both groups showed a remarkable ignorance of four decades of work leading to the conclusion that our genomes are full of junk DNA [see ENCODE, Junk DNA, and Intelligent Design Creationism ]. Creationists, and even some scientific opponents of junk DNA, quote Jonathan Wells' book The Myth of Junk DNA as an authority of the issue.
Now, I wrote a pretty extensive review of The Myth of Junk DNA showing where mistakes were made and why the evidence still favored lots of junk DNA in our genome [The Myth of Junk DNA by Jonathan Wells]. That was in 2011. Here's how Jonathan Wells responded ... [Jonathan Wells Sends His Regrets].
Oh, one last thing: “paulmc” referred to an online review of my book by University of Toronto professor Larry Moran—a review that “paulmc” called both extensive and thorough. Well, saturation bombing is extensive and thorough, too. Although “paulmc” admitted to not having read more than the Preface to The Myth of Junk DNA, I have read Mr. Moran’s review, which is so driven by confused thinking and malicious misrepresentations of my work—not to mention personal insults—that addressing it would be like trying to reason with a lynch mob.
The ENCODE Consortium has decided that it had better backtrack a little on the subject of junk DNA. Their recent PNAS article (Kellis et al., 2014) pretends that the publicity hype of September 2012 never existed and, even if it did, they may have been right to conclude that 80% of our genome is functional. It all depends on how you define function. Apparently they have just discovered that lots of scientists define it in a way that the ENCODE Consortium overlooked in September 2012.
Now they just want to make sure that everyone knows they have done their homework and they acknowledge that there's a wee bit of a controversy—but they weren't wrong! They just have a different way of defining function.
This puts some of the creationists in a difficult position. Some of them are actually willing to conceded that there's a lot of junk DNA in our genome while other are only willing to concede that the case for function may not be quite as rock solid as they thought.
Here's how an anonymous creationist explains the backtracking of the ENCODE Consortium on Evolution News & Views (sic): Defining "Functional": The Latest from ENCODE.
He/she starts off with the obligatory snipe at "Darwinists" and the obligatory misrepresentation of the case for junk DNA. He/she is referring to the Kellis et al. paper ...
First, the paper is a remarkably restrained and balanced response to some of the rather intemperate criticisms of ENCODE from hard-core Darwinists who insist that (a) ONLY an evolutionary approach yields valid information about functionality, (b) evolutionary theory necessarily implies that most of our DNA is junk, and (c) junk DNA provides evidence that Darwinian evolution is a fact. In other words this paper is a model of rational and civil scientific discourse, in contrast to what we have come to expect from some hard-core Darwinists.
(See the quote above from Jonathan Wells for an example of "a model of rational and civil scientific discourse.")
The Evolution News & Views post concludes with ...
The authors conclude that all three approaches must be taken into account, though a simple intersection of the three (which would include only DNA sequences that meet the test of functionality for all three approaches) would be far too restrictive. Unfortunately, the authors do not specify exactly how the three approaches could be integrated to yield a single reliable estimate of the percentage of functional DNA.
So the debate continues.
Believe it or not, that last sentence ("So the debate continues") is pretty remarkable considering that the creationists have steadfastly refused to admit that there is a scientific debate. Over the past decade, they have consistently claimed that the evidence is in and it shows that gods did it after all most of our genome is functional.
Maybe I'm being overly optimistic but it looks to me like some creationists are actually disagreeing with Jonathan Wells. Stay tuned.
Kellis, M. et al. (2014) Defining functional DNA elements in the human genome. Proc. Natl. Acad. Sci. (USA) April 24, 2014 published online [doi: 10.1073/pnas.1318948111 ]
Last week's molecules (right) [Monday's Molecule #237] were α-D-glucopyranosyl-(1➝4)-β-D-glucopyranose, the β anomer of maltose and α-D-glucopyranosyl-(1➝6)-α-D-glucopyranose, the β anomer of isomaltose. The winner is Dean Bruce. A surprising number of people got it right.
This week's molecules (below) are related. They are cytoplasmic (PDB 2P8U left) and mitochondrial (PDB 2WYA right) versions of very important enzymes. The human versions are shown. Name the enzymes and the products bound in the active sites (complete common name of the product). Mutations in one of the genes coding for one of these enzymes cause a rare genetic disease. Which one? Why are there no known diseases associated with genetic defects in the gene for the other version of the enzyme?
Email your answer to me at: Monday's Molecule #238. The first one with the correct answer wins. I will only post the names of winners 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.)
I'm in San Diego (California, USA) attending Experimental Biology 2014 (EB2014). This is a large meeting of several differnent societies. The one I belong to is ASMBM (American Society for Biochemisty & Molecular Biology).
I'm mostly interested in the sessions on teaching. The two I went to yesterday were on "Measuring Success in Undergraduate Education" and "Mentoring and Networking: Preparing for the Future."
There are far too many science talks. It's a bit overwhelming. I tend to focus on the plenary sessions where you can get an overview of a subject. This is where I'm most likely to find new material for my textbook. (No luck so far.)
All the cool people are here.
Here's Voet & Voet (Don Voet and Judy Voet). I also met John Tansey and several of the other authors on the paper covering ASMBM Core Concepts [see ASBMB Core Concepts in Biochemistry and Molecular Biology: Molecular Structure and Function ].
We've had some interesting discussions. I don't think I've convinced them, yet.
Sometimes you just want to throw up your hands and say something very rude. This is one of those times.
Salvador Cordova is trying to explain non-Darwinian evolution to his friends over on Uncommon Descent [Cost of maintenance and construction of design, neutral theory supports ID and/or creation].
Here's the punchline ....
But if most evolution is non-Darwinian, maintenance much less construction of design cannot be explained by Darwinism, then the case for ID is strengthened.
Now if most evolution had been non-Darwinian, one would rightly argue it would have been a random walk, and thus not much better than a tornado going trough a junkyard. Creationist have seized on this and said, "well we’re not a junkyards, therefore some non-random process must have created designs in nature, hence we are designed". In contrast, Larry Moran and friends have said "evolution is a random walk and we are obviously junkyards and you’re an IDiot if you think biological organisms are mostly functional."
It's very, very, difficult for me to believe that Cordova isn't lying through his teeth. He can't be that stupid, can he?
