Transcription of the 7SL Gene

Theme:
Transcription
There are five different kinds of RNA polymerase in eukaryotes. Each of them is responsible for transcription of a different class of gene [Eukaryotic RNA Polymerases]. RNA polymerase III transcribes a heterogeneous class of genes that give rise to small RNAs.


The class III genes can be subdivided into four types depending on the location of the promoter regions. Type 1 genes possess an internal control region (ICR) that functions as the promoter. What this means is that the site of binding of the pol III transcription complex is within the gene. 5S RNA genes are the only kind of type 1 gene.

A cartoon drawing of the pol III transcription complex on a 5S RNA gene is shown above (Moran, Scrimgeour et al. 1994). The transcription factor TFIIIA binds to the internal control region (ICR). Another transcription factor, TFIIIC, binds TFIIIA and it, in turn, interacts with TFIIIB and RNA polymerase III. Transcription is initiated at a site (+1) upstream from the internal control region. Note that when the 5S RNA is produced it will contain the binding sites for TFIIIA. The significance of this fact will become clear in a few minutes.

The type 2 genes have an intragenic promoter with two binding sites, A and B. TFIIIC binds directly to this promoter causing the assembly of a transcription complex upstream in the same manner as the type 1 genes. Most of the transfer RNA (tRNA) genes are type 2 genes.

Type 3 genes have an upstream promoter and no internal promoter. In this sense they resemble the typical class II genes (transcribed by RNA polymerase II), such as those that encode protein. The U6 snRNA gene, a component of the spliceosome [RNA Splicing: Introns and Exons] is the prototype gene of this category.

Finally, type 4 genes have both an internal region where the regular class III transcription factors bind and a promoter at the 5′ end of the gene where regulatory transcription factors bind to control transcription. The 7SL RNA gene is a type 4 gene.

Recall that 7SL RNA is the major component of Signal Recognition Particle (SRP). There are three genes for this RNA located on human chromosome 14 [Human Genes Involved in the Signal Hypothesis Pathway]. Since 7SL RNA is one of the small RNAs present in most cells it should not come as a surprise that its gene is transcribed by RNA polymerase III.


The RN7SL promoter has been characterized by Englert et al. (2004). The main features are shown in the diagram above. The solid blue box represents the gene—the DNA sequence corresponding to the 7SL RNA. There's a start site for transcription (+1) that's determined by the positioning of RNA polymerase III upstream. The transcription complex is assembled when TFIIIC binds to an internal control region specified by box A and box B. These are short DNA sequences (10 bp) that resemble the binding sites in tRNA genes. The upstream promoter region consists of a TATA box where RNA polymerase III binds and a regulatory site where unknown transcription factors (TF) bind.

Transcription terminates at a short stretch of thymidylate residues (T) at the 3′ end of the gene.

All four regulatory sites have to be present for maximum rates of transcription but—and this is important—there will still be low levels of transcription if only the A box and the B box are present.


From time to time cellular RNAs are copied by an enzyme called reverse transcriptase to create a DNA:RNA double-stranded molecule. On occasion this hybrid molecule will become integrated into the genome through a nonhomologous recombination event. (Sometimes the RNA strand will be replaced by DNA synthesis to create double-stranded DNA corresponding to the 7SL sequence.) This creates something called a processed pseudogene. Most genomes have hundreds of these pseudogenes derived from hundreds of different genes. They have arisen from accidental events over the course of millions of year of evolution and since there's no pressure to eliminate them, they are retained in the genome as junk.

Theme:
Junk DNA
If the processed pseudogene is derived from a class III gene there's a good chance that it will retain prompter activity because a good part of the promoter sequence was present in the RNA molecule. This is the case with 7SL pseudogenes and tRNA pseudogenes. They are often transcribed at low levels. The production of additional RNAs from the processed pseudogenes increases the probability that more pseudogenes will be created. More significantly, if the processed 7SL or tRNA pseudogenes happen to integrate near certain mobilization sequences they will be converted to retrotransposons because they can direct transcription of themselves—a necessary step in transposition. When this happens the pseudogenes will spread rapidly throughout the genome. We call this selfish DNA.

More than 10% of your genome consists of degenerate 7SL genes. That's where some of the junk DNA in your genome comes from.

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Englert, M., Felis, M., Junker, V. and Beier, H. (2004) Novel upstream and intragenic control elements for the RNA polymerase III-dependent transcription of human 7SL RNA genes. Biochimie. 86:867-74. [PubMed]

DNA Tatoo

 
Carl Zimmer has been collecting biological tattoos. The latest is a DNA tattoo [Science Tattoo Friday: A Textbook On Your Back]. Here's what the victim fan has to say ...

"My tattoo is from an Irving Geis illustration of DNA. I was attracted to his attention to the molecular detail while also drawing in a representational spiral that doesn't ignore the basic beauty of the double helix. This particular sequence (I've BLASTED) is too short to be specific to only one gene, but one human gene it's found it is the 5' UTR of one of our tight junctions."-Matthew MacDougall, 4th year medical student

The figure is, indeed, a drawing by Irving Geis. It's based on a structure of the dodecamer CGCGAATTCGCG solved by Drew et al. (1981). You can download the PDB file yourself at 1BNA and look at it in your favorite structure viewer. Mine is RasMol. The DNA is in the typical B-DNA form first predicted by Watson & Crick.

THEME

Deoxyribonucleic Acid (DNA)I've prepared two views of this structure (below) so you see how it compares to the Geis drawing. The drawing is in some textbooks, notably Voet & Voet Biochemistry 3rd ed. (p.1108). If you look closely, you will notice that Geis has taken a few "liberties" with his drawing. It's not quite the same as the actual molecular model but it's pretty close. I don't think our 4th year medical student has to worry about anyone noticing the difference, except for curmudgeonly biochemistry Professors!

Inflating a Little Man

 
TIME magazine gets it (mostly) right in a column by Joe Klein [Inflating a Little Man].

Well, at the top of the list are our old friends the neoconservatives, the folks who provided the intellectual rationale for Bush's war in Iraq, many of whom are now itching for a war with Iran. Norman Podhoretz, the neocon paterfamilias, has written a trifle called World War IV: The Long Struggle Against Islamofascism and loves to posit Ahmadinejad and Osama bin Laden—a far more dangerous character—as the heirs to Hitler and Stalin. "They follow the path of fascism, Nazism and totalitarianism," he writes. This is incendiary foolishness. Terrorists have the ability to wreak terrible damage intermittently, but they don't represent an existential threat to the U.S. Ahmadinejad commands no legions—not even the Hizballah forces in Lebanon that attacked Israel in the summer of 2006—and if Podhoretz doesn't know that, he should. Taking Ahmadinejad literally, as the neoconservatives do, is being disingenuous with lethal intent. It gives license to a conga line of politicians—especially Republicans running for �President—to strut their stuff by jumping on Ahmadinejad and Columbia University and liberals in general. Mitt Romney runs an ad in which he brags that he denied the milquetoast reformer Khatami a police escort to Harvard University in 2006. Now there's a man! The New York Daily News, owned by neoconservative Mort Zuckerman, runs the headline the evil has landed. The cable news networks hyperventilate. Even the president of Columbia University, Lee Bollinger, feels the need to demolish Ahmadinejad — elegantly, I must say — before the speech. A giant toxic bubble overwhelms the public square.

And then, there he is — and laughter is freedom's only appropriate reaction. The bubble bursts. He denies not only the Holocaust but also homosexuality? Suddenly, it all becomes obvious: We are being played by extremists on both sides. To be sure, Iran does arm Hizballah, and it does have an active nuclear program that may or may not be proved to have hostile intent, and it is making trouble for the U.S. in Iraq, supplying weapons to our enemies. These are all problems to be addressed soberly and perhaps even, eventually, with multilateral force. But the neoconservative campaign to transform Ahmadinejad into Hitler or Stalin, to pretend that he has the ability to destroy the world, to make a hoo-ha over letting the little man speak, is a cynical attempt to plump for war. Ahmadinejad may be ridiculous, but Podhoretz—who recently spent 45 minutes with Bush arguing for more war—isn't very funny at all. 

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[Hat Tip: John Wilkins at Evolving Thoughts (How to fix Iraq, and not invade Iran)]

US High School Dropout Rate

 
According to the University of Minnesota, the high school dropout rate in the USA is close to 25% [U of Minnesota study finds that US high school dropout rate higher than thought].

University of Minnesota sociologists have found that the U.S. high school dropout rate is considerably higher than most people think -- with one in four students not graduating -- and has not improved appreciably in recent decades. Their findings point to discrepancies in the two major data sources on which most governmental and non-governmental agencies base their findings.

The U.S. Census Bureau’s Current Population Survey (CPS) is widely used by governmental and non-governmental sources -- from the Annie E. Casey Foundation to the White House -- to report high school dropout rates. The CPS paints a rosy picture, showing dropout rates at about 10 percent in recent years and declining some 40 percent over the past generation. On the other hand, measures of high school completion based on the National Center for Education Statistics’ Common Core of Data survey (CCD) paint a darker picture, with high school completion rates holding steady at about 75 percent in recent decades.

Here's the important question that everyone seems to ignore: What is the optimal high school dropout rate? Surely it shouldn't be zero because that would be setting the bar too low. It probably shouldn't be 50% because that sets the bar too high. What should it be, assuming that lack of ability to complete high school was the only reason for dropping out?

If we're interested in keeping students in high school by addressing those other reasons for dropping out, then how will we know if we're succeeding unless we establish the minimum dropout rate? Is 25% good?

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[Photo Credit: "Joining nationwide demonstrations, high-school students in Valparaíso [Chile] take to the streets on May 30 [2006] to protest proposed changes in Chile's public education system." Eliseo Fernandez—Reuters /Landov (Encyclopedia Britanica Online)]

The Giardia lamblia Genome

 
The sequence of the Giardia lamblia genome has just been published in this month's issue of Science [Morrison et al., 2007].

Giardia lamblia is a single-celled eukaryote with two nuclei and prominent flagella (undulipodia, cilia) [Giardia lamblia, Wikipedia]. In most classification schemes it is placed in the Diplomonadida group, which may or may not be accorded the rank of phylum [Giardia lamblia NCBI Taxonomy]. Giardia is an intestinal parasite that colonizes the small intestine causing diarrhea and sometimes pain and nausea.

Many of the press releases focus on the medical relevance of the work on Giardia but the direct quotations from the scientists involved in the project reveal the real purpose behind this genome sequencing project. For example, Mitchell Sogin is quoted in the Marine Biogical Laboratory press release [Giardia Genome Unlocked].

“We embarked upon this genome project because of its importance to human health and suggestions from earlier molecular analyses that Giardia represents a very early-diverging lineage in the evolutionary history of eukaryotes,” Sogin says. “Giardia’s genome content and architecture support these theories about the parasite’s ancestral character.”

Sogin has a long standing interest in the evolution of eukaryotes and I think it's fair to say that Giardiasis is not the main focus of his research at the Marine Biological Laboratory in Woods Hole, Maine Massachusetts (USA) .

The Giardia lamblia genome is ~11.7 Mb in size (11,700,00 base pairs). This makes it about the same size as the yeast genome and the largest bacterial genomes. Mammalian genomes are about 200-300 times larger.

Preliminary results indicate 6470 genes distributed on five chromosomes. Most of the genes do not have introns and the average distance between genes is a few hundred nucleotides. What this means is that the genome is very compact with hardly any junk DNA (77% of the genome corresponds to coding regions as opposed to less than 2% in humans).

The number of genes is similar to the number found in yeast [Saccharomyces Genome Database (SGD)]. Multicellular species have 15-25,000 genes.

The introduction to the Morrison et al. (2007) paper has a nice summary of the main problems with relating Giardia to other eukaryotes.

Unusual features of this enigmatic protist include the presence of two similar, transcriptionally active diploid nuclei and the absence of mitochondria and peroxisomes. Giardia is a member of the Diplomonadida, which includes both free-living (e.g., Trepomonas) and parasitic species. The phylogenetic position of diplomonads and related excavate taxa is perplexing. Ribosomal RNA (rRNA), vacuolar ATPase (adenosine triphosphatase), and elongation factor phylogenies identify Giardia as a basal eukaryote (2–4). Other gene trees position diplomonads as one of many eukaryotic lineages that diverged nearly simultaneously with the opisthokonts and plants. Discoveries of a mitochondrial-like cpn60 gene and a mitosome imply that the absence of respiring mitochondria in Giardia may reflect adaptation to a microaerophilic life-style rather than divergence before the endosymbiosis of the mitochondrial ancestor.

Originally, it was thought that Giardia must be part of a group that diverged very early on in eukaryotic evolution, before other lineages acquired mitochondria. However, in the past ten years or so these amitochondrial species have been shown to contain genes that are clearly derived from mitiochondria (e.g., cpn60, dnaK). Thus, it now appears that these species have lost their original mitochondria, calling into question their position at the root of the eukaryotic tree.

One of the main surprises is the confirmation of what had long been suspected: Giardia is missing some common eukaryotic genes. The title of the paper highlights this finding: "Genomic Minimalism in the Early Diverging Intestinal Parasite Giardia lamblia."

In many cases the protein machines in Giardia are simpler than those in other eukaryotes and some key metabolic enzymes are not present. Is this a derived phenomenon resulting from a parasitic lifestyle or is it indicative of a primitive state in eukaryotic evolution?

Morrison et al. (2007) indicate their preference ...

As discussed earlier, Giardia consistently shows a pattern of simplified molecular machinery, cytoskeletal structure, and metabolic pathways compared to later diverging lineages such as fungi and even Trichomonas or Entamoeba (Supporting Online Material; table S7 and fig. S5). A parsimonious explanation of this pattern is that Giardia never had many components of what may be considered "eukaryotic machinery," not that it had and lost them through genome reduction as is evident for Encephalitozoon. Taking a whole-evidence approach, one sees that these data reflect early divergence, not a derived genome.

They attempt to construct phylogenetic trees based on a number of newly sequenced genes but immediately encountered problems.

Phylogenetic inference alone cannot resolve Giardia's evolutionary history. Because so many of Giardia's genes may have been derived from horizontal transfer or be subject to accelerated evolution, only a subset can be used to infer phylogeny. Of the ~1500 genes for which there are known homologs, only a handful included diverse eukaryotic taxa and generated robust trees, largely because the sequences could not be unambiguously aligned. We generated and examined trees for many conserved proteins, and selected ribosomal proteins for a multigene data set because they are an ancient family, whose nature—interaction with rRNAs and with all cellular proteins during their synthesis—constrains their divergence.

Their data suggests that Giardia and its close relatives form a lineage that branches deeply in the eukaryotic tree suggesting that they diverged very early on in eukaryotic evolution (above, from the supplemental data). (Probably close to two billion years ago.)

In an article accompanying the original paper, Keeling (2007) discusses the implications. He includes the phylogenetic tree shown here [Deep Questions in the Tree of Life].

Eukaryotic evolution. The hypothetical evolutionary tree consists of five "supergroups" based on several kinds of evidence (15). The branching order of supergroups is unresolved, implying that the relationships are unknown rather than a simultaneous radiation. CM indicates the presence of cryptic mitochondria (hydrogenosomes or mitosomes). A question mark indicates that no organelle has yet been found.

This is not a consensus tree by any stretch. The existence of the five groups is hotly contested and it remains to be seen whether these groupings will gain widespread support. Notice that Keeling does not commit to a branching order for the five groups in spite of the conclusions of Morrison et al. (2007) in the paper he is reviewing.

What is clear is that the old trees based on ribosomal RNA genes are not reliable and other genes will have to be examined in future work. That's the real significance of the Giardia lamblia genome sequence and the sequences of the genomes of other simple eukaryotes. Given that Giardia is missing some important genes—posibly because of its parasitic lifestyle—this may not be an easy task. Keeling (2007) sums it up like this ....

The outcome of this debate affects not only our understanding of early eukaryotic evolution, but also our view of Giardia biology. Simple characteristics could be primitive or derived via reduction, alternatives with very different meanings. The simplicity of Giardia's molecular systems differs from that of known derived parasites (1, 13). However, different lineages can follow different reductive paths (14), so determining Giardia's origins independently of its simplicity is essential. Given the depth of these questions, the new life that Morrison et al. have breathed into the debates is welcome, and will ensure continued attention on both a fascinating cell and the origin of eukaryotes.

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[Photo Credits: The life cycle diagram is from the National Institutes of Health (USA) (Wikimedia Commons). The scanning electron micrograph of Giardia is from the Centers for Disease Control and Prevention (USA) (Wikimedia Commons)]

Morrison, H.G., McArthur, A.G., Gillin, F.D., Aley, S.B., et al. (2007) Genomic Minimalism in the Early Diverging Intestinal Parasite Giardia lamblia. Science 317:1921 - 1926. [Science]

Keeling, P.J. (2007) Deep Questions in the Tree of Life. Science 317:1875-1876. [Science]

I Wish I Could Be There to See the Flaming Framing

 
SPECIAL EVENT:
Speaking Science 2.0: New Directions in Science Communications
Friday, September 28, 2007
7:30 p.m.
Bell Museum Auditorium
$5 Suggested Donation

Seed magazine writers and influential science bloggers gather to discuss new directions in science communication. This lively panel discussion will cover a range of topics, including science and culture, public engagement with science, the role of scientists in the public discussion of science, and communication via the Internet, film, museums and other media. Author and journalist Chris Mooney, American University communications professor Matthew Nisbet, and University of Minnesota anthropologist Greg Laden will join moderator Jessica Marshall, a U of M science journalism professor. A reception in Dinkytown will follow the event. Co-sponsored by the Bell Museum of Natural History; Seed Magazine/ScienceBlogs; The Humphrey Institute's Center for Science, Technology and Public Policy; and the Minnesota Journalism Center.

Will PZ Myers be there?

Danger on the Southern Border

 
From CNN.com comes scary news about our southern border [ Report: Security on U.S.-Canada border fails terror test].

WASHINGTON (CNN) -- A terrorist wanting to smuggle radioactive material from Canada into the United States probably would find it easy to do, a new report from congressional investigators said.

Government investigators were able to cross from Canada into the United States carrying a duffle bag with contents that looked like radioactive material and never encountered a law enforcement official, according to a report released Thursday by investigators from the Government Accountability Office.

"Our work clearly shows substantial vulnerabilities in the northern border to terrorist or criminals entering the United States undetected," the GAO's Greg Kutz testified Thursday at a Senate Finance Committee hearing on the topic.

"Although the southern border appears to be substantially more secure, we did identify several vulnerabilities on federally managed lands where there was no CBP [Customs and Border Protection] control."

It's our Southern border we Canadians should be worried about. There are far more terrorists in American than in Canada. Wake up Canadians! Don't you realize that terrorists from the USA could be infiltrating our country as we speak!? They're out to attack us because we're free ... well maybe not "free" but at least we're cheap now that the Canadian dollar has reached parity.

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[Photo Credit: A border marker shows you where Canada ("left", or maybe right) meets the USA (right, I think) near Blumenort, Manitoba]

Nations must fight climate change like terrorism, Rice says

 
From CNN [ Nations must fight climate change like terrorism, Rice says].

WASHINGTON (CNN) -- U.S. Secretary of State Condoleezza Rice on Thursday told delegates to a global climate change conference that countries around the world must work together to combat climate change, much as they cooperate against terror and the spread of disease.

"No one nation, no matter how much power or political will it possesses, can succeed alone," she said. "We all need partners, and we all need to work in concert."

Rice said the United States takes climate change seriously, "for we are both a major economy and a major emitter."

Other nations have been critical of the Bush administration's policy on climate change after the United States withdrew from the 1997 U.N. Framework Convention on Climate Change, known as the Kyoto Protocol. More than 150 countries signed the Kyoto agreement, which mandates limits on emissions.

Fight climate change like we fight terrorism. Work together, but drop out of Kyoto. No further comment is necessary. It saddens me that my Prime Minister is falling for this nonsense.

[Photo Credit: CBC News]

Who's Reading Sandwalk Right Now?

 
I was curious about when people were reading Sandwalk. Sometimes I get into chat mode with some of you in the comments section. It seems that some people have a schedule similar to mine.

Then I got to thinking. Maybe everyone in Europe reads during the night and everyone in Australia during the day—or some such permutation. So I took a snapshot of where my readers are at different times of the day/night.

Here are the results for 1PM, 5PM, 11PM, and 6AM respectively. There doesn't seem to be a pattern except that most of you are asleep between midnight and 6AM your time. It looks like you're surfing the internet most of the time you're awake! (BTW, who's that person in Hawaii? I'd like to visit you. Do you have a spare room?)

Polycystic Liver Disease

 
Polycystic liver disease (PLD) is associated with the formation of multiple cysts of various sizes in the liver. Sometimes it causes enlargement of the liver and abdominal pain but in most cases there are no symptoms and the patient may be unaware of any problem.

This disease is not the same as the often fatal polycystic kidney disease (PKD) [OMIM 173910] although patients suffering from kidney failure due to PKD will often have cysts in their liver as well.

PLD is inherited as an autosomal dominant trait, which means that you will have liver cysts even if you only inherit one mutant allele from one parent. There are probably several different genes that can be affected but two genes have been identified and characterized [OMIM 174050]. One of them is the SEC63 gene on chromosome 6q21 [OMIM 60648][Entrez Gene 11231]. This gene encodes one of the components of the ER membrane translocon. This is the pore through which newly synthesized is threaded following attachment of the ribosome/signal-recognition-particle complex [Signal Hypothesis] [Human Genes Involved in the Signal Hypothesis Pathway]. The defect in SEC63 probably interferes with sorting and secretion of proteins in the liver and this is what causes the cysts.

The Online Medelian Inheritance in Man (OMIM) database at Johns Hopkins University is one of the best databases in the world.
The known alleles are null mutations meaning that they disrupt synthesis of the protein. It appears that the presence of one defective copy of the SEC63 gene has no effect on normal development or secretion in most tissues but does have a non-lethal effect in liver cells.

The other gene that's associated with polycystic liver disease is PRKCSH, a gene that encodes the β subunit of glucosidase II [OMIM 177060]. This protein plays a role in the glycolsylation of proteins in the endoplasmic reticulum [glycosylation]. Since glysosylation is requried for protein sorting and secretion, it is likely that interference in that process is resposible for liver cycsts. This is the same process that's defective in SEC63 mutants.

[Photo Credit: OSF Heathcare]

Human Genes Involved in the Signal Hypothesis Pathway

 
The Signal Hypothesis describes the mechanism whereby proteins that are destined to cross a membrane are synthesized. One of the key components of this pathway is Signal Recognition Particle or SRP. The structure of SRP is shown below from a paper by Maity and Weeks (2007)

Most of SRP is composed of an RNA molecule called 7SL RNA. It is shown as red and yellow helices in the bottom figure. The secondary structure is depicted in the top right-hand corner of the figure. There are six different proteins in SRP. All of them are bound to the RNA in one way or another. The six proteins are SRP9, SRP14, SRP54, SRP68, and SRP72. The numbers refer to the molecular mass in kilodaltons.


There are three genes for 7SL RNA. They are all found on chromosome 14 (above). Two of them are closely linked and the third one is somewhat farther away.

• RN7SL1: Entrez Gene 6029. Chromosome 14q22.1
• RN7SL2: Entrez Gene 378706. Chromosome 14
• RN7SL3: Entrez Gene 378707. Chromosome 14

The genes for the protein components are:

• SRP9: Entrez Gene 6726. Chromosome 1q42.12
• SRP14: Entreez Gene 6727. Chromosome 15q22
• SRP54: Entrez Gene 6729. Chromosome 14q13.2
• SRP68: Entrez Gene 6730. Chromosome 17q25.1
• SRP72: Entrez Gene 6731. Chromosome 4q11

The three membrane components are the SRP receptor, the translocon (formerly known as ribophorin), and the signal peptidase. There are two subunits in the SRP receptor, α (docking protein) and β. The human genome contains a single gene for SRP receptor α subunit called SSPR (SSPRα). The genome has two separate genes for the β subunit called SSRB and SSR2.

• SSPR (Docking protein) (SSRα): Entrez Gene 6734. Chromosome 11q24.3
• SRPRB: Entrez Gene 58447. Chromosome 3q22.1
• SSR2: Entrez Gene 6746. Chromosome 1q21-q23

The translocon is composed of three proteins; SEC61, SEC62, and SEC63. The SEC61 protein has three subunits; α (genes SEC61A1 and SEC61A2), β (gene SEC61B), and γ (gene SEC61G).

• SEC61A1: Entrez Gene 29927. Chromosome 3q21.3
• SEC61A2: Entrez Gene 55176. Chromosome 10p14
• SEC61B: Entrez Gene 10952. Chromosome 9q22.32-q31.3
• SEC61G: Entrez Gene 23480. Chromosome 7p11.2
• TLOC1 (SEC62): Entrez Gene 7095. Chromosome 3q26.2
• SEC63: Entrez Gene 11231. Chromosome 6q21

Finally, there are three subunits of the signal peptidase complex encoded by SPCS1 (signal peptidase complex, subunit 1), SPCS2, and SPCS3.

• SPCS1: Entrez Gene 28972. Chromosome 3q22.1
• SPCS2: Entrez Gene 9789. Chromosome 1q21-q23
• SPCS3: Entrez Gene 60559. Chromosome 11q24.3

There are 20 genes required for effective translocation of proteins with a signal sequence (only the SRP are shown on the chromosome maps). Additional proteins are required to assist in the translocation (chaperones) and in glycosylation of the protein once it enters the lumen of the endoplasmic reticulum.

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Maity, T.S. and Weeks, K.M. (2007) A threefold RNA-protein interface in the signal recognition particle gates native complex assembly. J. Mol. Biol. 369:512-24 [PubMed]

Iranian Army Is a Terrorist Organization - What's This All About?

 
The New York Times reports on a recent US Senate resolution.

The Senate approved a resolution today urging the Bush administration to designate Iran’s Islamic Revolutionary Guard Corps as a foreign terrorist organization, and lawmakers briefly set aside partisan differences to approve a measure calling for stepped-up diplomacy to forge a political solution in Iraq.

Since last month, the White House has been weighing whether to deem the entire Revolutionary Guard as a terrorist group or to take a narrower step focused only on the Quds Force, an elite unit of the corps. Either approach would signal a more confrontational posture by declaring a segment of the Iranian military to be a terrorist organization.

Saying that it's "confrontational" is putting it mildly. Is there a logical reason for doing this? Here's what General Petraeus says,

It quoted General Petraeus as saying it is “increasingly apparent to both coalition and Iraqi leaders that Iran, through the use of the Iranian Republican Guard Corps Quds Force, seeks to turn the Shiite militia extremists into a Hezbollah-like force to serve its interests and fight a proxy war against the Iraqi state and coalition forces in Iraq.”

Ahhh .... now I get it. We have a case where foreign soldiers in Iraq might be helping certain militia groups in order to serve its own interests and fight a proxy war against its perceived enemies. All soldiers who do that are terrorists, right?

Makes a lot of sense to me.

As an aside, I note that the US Congress is a lot more confident about military intelligence these days. I guess the fiasco of Colin Powell's UN Presentation on February 6, 2003 has been forgotten in light of a vastly improved intelligence gathering network. We can now be confident that all pronouncements about the evil axis countries are accurate, right?

[Photo Link: U.S. Special Forces Secure Tribal Sheikhs Meeting In Diyala Google.]

Conservative Think Tanks

 
Conservative think tanks have been wrong about so many things in the recent past it's a wonder anybody still pays attention. Bill Maher gets it in a show that aired last winter.



[Hat Tip: Canadian Cynic.]

Plants, not Fungi, Are Most Closely Related to Animals?

 
The American Society for Biochemistry & Molecular Biology has drawn up guidelines for a new curriculum in undergraduate education. The complete recommendation can be found at Recommended Curriculum for a Program in Biochemistry and Molecular Biology in the Journal Biochemistry and Molecular Biology Education (BAMBED).

Under the list of "Skills that biochemistry and molecular biology students should obtain by the time they have finished their undergraduate program," there are a number of motherhood type statements. One of them is "Ability to assess primary papers critically." We've been discussing these required skills for the past few months. I've questioned the wisdom of teaching undergraduates how to critically evaluate the scientific literature because I think it's a skill that only comes after a lot of experience in the discipline.

There are many confusing papers out there and it's difficult to decide what's right and what's wrong. We can give students our opinion but that's not the same as teaching them how to critically evaluate a paper.

Here's an example of how difficult it is to read the scientific literature. A recent paper by John Stiller (2007) promotes the idea that plants are more closely related to animals than fungi. Here's the abstract.

Evolutionary relationships among complex, multicellular eukaryotes are generally interpreted within the framework of molecular sequence-based phylogenies that suggest green plants and animals are only distantly related on the eukaryotic tree. However, important anomalies have been reported in phylogenomic analyses, including several that relate specifically to green plant evolution. In addition, plants and animals share molecular, biochemical and genome-level features that suggest a relatively close relationship between the two groups. This article explores the impacts of plastid endosymbioses on nuclear genomes, how they can explain incongruent phylogenetic signals in molecular data sets and reconcile conflicts among different sources of comparative data. Specifically, I argue that the large influx of plastid DNA into plant and algal nuclear genomes has resulted in tree-building artifacts that obscure a relatively close evolutionary relationship between green plants and animals.

This position is contrary to a whole lot of work that has been published over the past several decades. I don't think very much of this paper and neither do John Logsdon of Sex, Genes & Evolution [Promoting Plants at the Expense of Fungi?] and Ryan Gregory of Genomicron [Discovery wants to "demote" fungi]. Read their blogs to see why we're skeptical about this paper.

How do you explain this to undergraduates? How can you teach them to critically evaluate such a paper when, on the surface, it seems perfectly reasonable and the data seems sound? I submit that most of us work within a model of how we think the history of life has developed over millions of years. That model is based on reading hundreds of papers and getting a "feel" for the data. Some papers are rejected and some are given more credence and this is based on all kinds of intangibles—including the reputation of the authors. Can undergraduates be taught such a thing? I don't think so.

Tangled Bank #89

 

The latest version of the Tangled Bank has been posted on Aardvarchaeology [Tangled Bank #89].