Transposons: Part II

 
There are many eukaryotic transposons that resemble the simple bacterial transposons described in Transposons: Part I. The classic examples are the P-factor transposon in Drosophila melanogaster and the AC-like elements in maize.

Both of these transposons have many of the characteristics of the bacterial transposons including the presence of a transposase gene. Like the bacterial transposons described earlier, this type of transposon jumps from one location to another. The original genome site is restored when the transposon is excised.

Transposons were first discovered in plants because there are many plant transposons that are quite active (they jump a lot) and they frequently land in genes that become disrupted. The disrupted gene can cause a visible phenotype that plant breeders have taken note of.

One example is shown on the left. The top figure is a yellow (colorless) kernel of corn. The wild-type purple color is not produced because of a transposon (Spm) inserted into one of the genes for the production of the pigment anthocyanin. Unfortunately for the plant breeder, this mutant isn't stable and from time to time the kernels "revert" back to purple as shown in the lower figure. The purple color is not evenly distributed because the "reversion" only occurs in small clusters of cells.

It was Barbara McClintock who first recognized that this pattern was due to "jumping genes" back in the 1940's. She based her conclusions on work she was doing with a number of genes in corn where the genetics could not be reconciled with standard Mendelian transmission. We now know that the reversion to production of anthocyanin is due to excision of the Spm transposon that was disrupting the gene. This excision occurs spontaneously in the somatic cells during the development of the kernel. McClintock received the Nobel Prize in 1983 for the discovery of mobile genetic elements.

There are many other examples of transposon mediated mutations in plants, as well as in other eukaryotes, such as yeast and Drosophila melanogaster. Another plant pigment example was shown in Monday's Molecule #45. The picture of the patterned petunia flower is reproduced below. It is taken from University of Bern website.

The pattern of colored stripes seen in petunia flowers (left) is due to the presence of transposon Tph1. The species Petunia hybrida line W138 contains a disrupted rt locus due to the insertion of transposon dTph1 (Kroon et al. 1994). The mutation blocks production of anthrocyanin pigments and gives rise to a white flower.

During development of the flower, the Tph1 transposon excises in certain cells and pigment production is restored. The pie-shaped pattern of cells reveals that the flower grows outward from a small number of cells in the center of the primordial flower head.

The W138 line can be used to isolate additional mutants since Tph1 excises and reintegrates into other genes at an appreciable rate (van Houwelingen et al. 1998).

Plant genomes harbor many transposons since they have a huge amounts of junk DNA where transposons can hide without causing damage. In fact, much of this junk DNA may have originated from ancient transposons that acquired mutations rendering them unable to excise and jump to another site. Over time other transposons inserted themselves into the defective transposons and the amount of junk DNA grew. The recent sequencing of the genomes of several plants has revealed an abundance of sequences related to transposons. These sequences appear to be inactive.

---

[Photo Credit: The pictures of the corn kernels are from Moran, Scrimgeour et al. Biochemistry 1998.]

Kroon, J., Souer, E., de Graaff, A., Xue, Y., Mol, J. and Koes, R. (1994) Cloning and structural analysis of the anthocyanin pigmentation locus Rt of Petunia hybrida: characterization of insertion sequences in two mutant alleles. Plant J. 5:69-80. [PubMed]

van Houwelingen, A., Souer, E., Spelt, K., Kloos, D., Mol, J. an Koes, R. (1998) Analysis of flower pigmentation mutants generated by random transpson mutagenesis in Petunia hybrida. Plant J. 13:39-50. [PubMed]

Transposons: Part I

 
Transposons are segments of DNA that can move (transpose) within the genome. They are also known as mobile genetic elements, transposable elements, jumping genes, or selfish DNA. Transposons often encode the enzymes necessary to catalyze their relocation and duplication in the genome. They don't usually have any function other than replicating themselves and jumping around in the genome. That's why they're sometimes called "selfish DNA." Selfish DNA is not the same as the "selfish genes" of Richard Dawkins. Those are real genes that perpetuate themselves through a beneficial effect on the organism they inhabit.

There are many different types of transposon. The best characterized ones are found in bacterial genomes where they are called insertion elements (IS). An example is shown below.
This example exhibits most of the characteristics of simple transposons. The grey bars at each end represent the genomic DNA into which the transposon is inserted. The yellow bars indicate a short stretch (~5 bp) of genomic DNA that's repeated on either side of the insertion element. This short repeat is almost always associated with insertion and excision of the transposon and it's a diagnostic feature of mobile genetic elements.

The red bars are inverted repeats at the ends of the transposon. This is another feature that's common to most transposons and it is required for copying and insertion/excision. This particular example contains a gene for the enzyme "transposase" (green).

The mechanism of transposition is shown in the figure below. Transposase catalyzes the excision of the transposon from the genome. It also cuts the DNA at the target site creating staggered ends with single-strand extensions, much like the cleavage sites of some restriction endonucleases [Restriction, Modification, and Epigenetics].


The excised transposon is integrated into the DNA that has been cut at the target site, then the single-stranded gaps are filled in by DNA polymerase and sealed by DNA ligase. The result is an integrated transposon with a short stretch of duplicated genomic DNA at each end.

In this case, the transposon can really be said to "jump" from one location to another. The original site is completely restored and the transposon moves to another location.

Many bacteria contain composite transposons that contain additional genes. The best known ones are those that carry genes for drug resistance, such as tetracycline resistance (transposon Tn10) or chloramphenicol resistance (Tn9). One of the reasons why drug resistance spreads in bacterial populations is because the resistance gene is on a mobile genetic element that can integrate into foreign DNA or into a plasmid that can be readily transferred.

There are usually not many transposons in a typical bacterial genome. This is because there are not many sites of integration that aren't lethal. In most cases when a transposon jumps it lands in a gene and inactivates it. This is usually lethal. Thus, most bacterial transposons reside in parts of the genome that are non-essential and there isn't much of that in bacteria.

Genomes that contain lots of non-essential DNA (junk) are likely to carry many transposons.

Mythical PNAS Papers

 
Here's part of a Harvard University Press release issued yesterday.

Beyond a 'speed limit' on mutations, species risk extinction

Genomes of various organisms lose stability with more than 6 mutations per generation

CAMBRIDGE, Mass. -- Harvard University scientists have identified a virtual "speed limit" on the rate of molecular evolution in organisms, and the magic number appears to be 6 mutations per genome per generation -- a level beyond which species run the strong risk of extinction as their genomes lose stability.

By modeling the stability of proteins required for an organism's survival, Eugene Shakhnovich and his colleagues have discovered this essential thermodynamic limit on a species's rate of evolution. Their discovery, published this week in the Proceedings of the National Academy of Sciences, draws a crucial connection between the physical properties of genetic material and the survival fitness of an entire organism.

This sounds very interesting. The limit of six mutations per genome per generation is far less than the calculated mutation rates for mammalian genomes [Mutation Rates] so it looks like another genetic load argument in favor of junk DNA.

So, I set off to retrieve the article that, according to the press release was published in this week's issue of PNAS. But it wasn't. You can see for yourself by looking at the current issue on the website [Sept. 25, 2007].

Not a problem. I've encountered this discrepancy before. What they mean is the issue that's about to be published and the article is available online in prepublication format. All you have to do is check the "Early Edition" (in this case the Oct. 2, 2007 edition) by clicking on the link from the PNAS home page. Except that the paper isn't there either.

Thus, in spite of what it says in the press release, this paper has not been published by PNAS in either the paper issue or online. This is not the first time this has happened. Over the past few months I've tried to find half a dozen mythical PNAS papers that are prominently mentioned in press releases.

Wait a minute ... look at the fine print on the early edition page [Early Edition]. The version that I'm looking at right now says "Last updated October 2, 2007." Right below that is the following statement.

Because PNAS publishes daily online, you may read about an article in the news media on Monday or Tuesday, but the article may not publish online until later in the week. You may use the CiteTrack feature to set up an e-mail alert to notify you as soon as the article you are interested in publishes.

This is unacceptable. If PNAS can't guarantee that a paper will be available when the press release embargo is lifted then they should change the embargo date. Most other journals have a restriction on press releases that delays the promotion of a paper until it is published and we can see for ourselves whether the hype and the reality match. Apparently PNAS is aware of this problem but instead of fixing it by moving the embargo date to Friday they choose to ignore publishing etiquette. This is wrong.

Three Cheers for October's SEED Magazine

 
One of my pet peeves is the misuse of the term "Central Dogma of Molecular Biology" [Basic Concepts: The Central Dogma of Molecular Biology]. Most people define it as the flow of information from DNA to RNA to protein. Many then go on to declare that the Central Dogma has been overthrown because of reverse transcriptase, alternative splicing, microRNA, epigenetics, or whatever.

This month's issue of SEED has a tear-out summary (cribsheet) of "Genetics." In one of the boxes titled "The Central Dogma of Molecular Biology" there's a drawing of the major pathways of information flow. The caption says.

There are nine ways information can theoretically flow between DNA, RNA, and protein. Of these, three are seen throughout nature, DNA to DNA (replication), DNA to RNA (transcription), and RNA to protein (translation). Three more are known to occur in special circumstances like viruses or laboratory experiments (RNA to RNA, RNA to DNA, and DNA to protein). Flows of information from protein have not been observed. The trend is clear: information flow from DNA or RNA into protein is irreversible. This is known as the "central dogma," and forms the foundation of molecular biology.

Yeah! As far as I know this is the only popular magazine to get it right.

MMP: Debunking the Myths, Chastising the Fearmongers

 


The amount of misinformation being spread about the Mixed Member Proportional voting system is truly frightening. I thought the citizens of Ontario deserved better than that. This is an important referendum and it shouldn't be decided by people who misrepresent the truth. There are legitimate arguments on both sides of the issue but it would be a real shame if voters were frightened into rejecting MMP by lies and distortions.

I've already tried to explain why the Sunday Toronto Star was wrong in its editorial [The Toronto Star Endorses First-Pass-the-Post], but others have done a better job.

Here's an article in The National Post by Andrew Coyne [PR:Debunking the fearmongers]. Coyne says,

... we are told that changing the system will result in chronic instability, a series of minority governments, one falling after the other; or else that it will lead to chronic gridlock, a legislature divided into dozens of smaller parties, some extremist, who would use their bargaining power to hijack the political process, demanding that one or other of the mainstream parties adopt their agenda in return for their support. The spectre of Israel and Italy are often invoked, as if to cinch the argument.

We can dispose of the last easily enough. One: Israel and Italy are uniquely divided societies, and were long before they adopted PR. Two: Neither country has ever used anything like the mixed system proposed for Ontario, but rather adopted much more extreme forms of PR, with no threshold for support.

As for the more specific fears, they would perhaps be more tenable were we the first country ever to try proportional representation -- were it not already in use, in one form or another, in most of the democratic world. But in fact it is, and in no country have any of the scare stories come to pass.

Read the entire article to see just how misleading the opponent of MMP have become.

Then there's the press releases on the Vote for MMP website. The first one addresses the claim that party lists would be drawn up by party bosses and would favor hacks. This accusation was made in the Toronto Star editorial, but it's popular fodder for all opponents of MMP. Here's the truth from REALITY CHECK: VOTEFORMMP.CA CALLS ON TORONTO STAR TO CLEAN UP MISLEADING REPORTING.

VoteForMMP.ca is accusing the Toronto Star of fear-mongering and inaccurate journalism in the Star's editorial today against electoral reform.

In today's editorial, the Toronto Star repeated the misleading claim that under Ontario's proposed new MMP system, the new province-wide candidates “could simply be appointed by party bosses.”

"This argument is regularly being used falsely by unthinking defenders of the status quo to deter support for needed electoral reform," said Rick Anderson, campaign chair of VoteForMMP.ca. "It's a shame that a media organization with the Star's credentials is not more careful with the facts regarding such an important question confronting voters."

...

In today's system, parties are left to determine their own methods for democratically nominating local candidates. Likewise, the Citizens’ Assembly left it to the individual parties to determine their own methods of nominating both riding and provincial candidates in the future, with the provisos that the parties are required to nominate their candidates publicly before voters vote and to publish the details of their candidate nomination processes in a clear, democratic and transparent fashion.

"In the other jurisdictions which use MMP all parties have adopted democratic candidate nomination processes for proportional candidates, just as they have for local candidates. Moreover, even in advance of the new system being adopted three of Ontario's four parties have already made public statements affirming they will follow democratic practices to nominate MMP candidates." (See backgounder below.)

"The notion that under MMP candidates would be appointed is simply hogwash," said Anderson. "Star readers should demand greater accuracy from their paper. Informed voters require a higher standard than this inaccurate sloganeering."

The important point here is that Ontario parties will almost certainly adopt democratic practices in drawing up their lists. It makes sense and it's what other countries do. Let's not hear any more fearmongering about party lists. From now on, people who use that argument are not guilty of mere ignorance.

What about the idea that a Mixed Member Proportional voting system would lead to political chaos? This is another of the arguments used in the Toronto Star editorial and it's widely believed to be true. Here's the real truth based on available facts [REALITY CHECK #2 TORONTO STAR WRONG ABOUT WHETHER FPTP OR MMP LEADS TO POLITICAL CHAOS].

VoteForMMP.ca says the Toronto Star owes it to voters to do its homework on whether first-past-the-post (FPTP) or mixed member proportional (MMP) leads to better political consensus.

In an editorial today, the Toronto Star claimed that “Jurisdictions that have adopted some form or other of proportional representation – think of Italy, Israel, Germany, Belgium – have become notorious for chaotic politics and legislature gridlock.”

More than 80 countries use proportional voting systems, with some for more than a century. If colourful anecdotes suffice for “evidence”, does that mean Zimbabwe or Nigeria prove that FPTP is “notorious” for producing oppressive and corrupt regimes?

The respected comparative studies show countries with proportional representation enjoy stable, effective, representative, accountable governments, which tend to produce legislation more in line with majority viewpoint while maintaining strong economic performance.

Notwithstanding colourful politics, Italy is actually a fairly stable and successful country, as vibrant in its political culture as it is in so many other ways, and hardly a failing state. The periodic reorganizations of its governing coalitions are sometimes colourful to be sure, but are generally accomplished without elections or even changes of government, more akin to what we think of as cabinet shuffles than anything else. (See: minority governments in Canada for more disruptive examples of chaos). Where does the Star get off treating Italy this way - and forgiving what happens here in Canada when voters are divided in their preferences?

Germany is an example which directly disproves the Star's supposed point. When the 2005 elections produced a split outcome, and smaller parties demanded high concessions as the price of coalition support, the two largest parties instead agreed to collaborate together in forming a successful government. The Star should check its facts.

...

The Star is perpetuating two misleading myths: one that FPTP is relatively stable and the other that PR is not. The facts are generally the opposite of the Star's comfortable prejudice in favour of the status quo.

Gathering of the Godless

 
"Gathering of the Godless" is one of the subtitles in an ABC News story about last weekend's atheist meeting in Virginia (USA) [The Rise of Atheism].

For another, more interesting, version read Hermant's summary on FriendlyAtheist [Atheist Alliance International Convention 2007 (Recap)]. Find out he got to be Daniel Dennett.

Superoxide Dismutase Is a Really Fast Enzyme

PhilipJ has posted the latest "Molecule of the Month" on Biocurious [Molecule of the Month: Superoxide Dismutase]. The molecule is superoxide dismutase from cow (Bos taurus) drawn by David Goodsell from the 2SOD (formerly 1SOD) structure in the Protein Data Bank. This structure is from 1980.

The formal name of this enzyme is copper-zinc superoxide dismutase in order to distinguish it from other, unrelated, superoxide dismutases. As noted on the Biocurious website, the main reason for having this enzyme is to get rid of dangerous free radical forms of oxygen that are produced in a number of cellular reactions; notably, membrane-associated electron transport and photosynthesis. (Superoxide dismutase is found in all species.)

The reaction involves a copper ion (Cu²⁺) at the active site of the enzyme (E). A free radical, such as the toxic superoxide radical anion, binds to the coper ion and an electron is transferred from the superoxide radical to the copper ion. This leads to the reduction of the copper ion from the +2 form to the +1 form as it picks up a single negative charge from the electron. In the second step, this electron is passed from the copper ion back to another superoxide anion which then combines with two protons to make hydrogen peroxide (H₂O₂). Hydrogen peroxide can be easily converted to water + molecular oxygen by ubiquitous catalase enzymes.


Superoxide dismutase is an important enzyme and it's role in scavenging free radicals would be more than enough to justify its inclusion in biochemistry textbooks. But there's another reason why this enzyme is discussed. It's one of the fastest enzymes known to biochemists as shown in the table below.



I suspect that most of you aren't familiar with the Michaelis-Menten constants k_cat and K_M but that doesn't matter. Trust me, these are very fast enzymes.

In fact, superoxide dismutase is faster than it has any right to be. The maximum rate of an enzymatic reaction was thought to be limited to the rate of diffusion inside the cell. This makes sense since the substrate (superoxide anion) has to collide with the active site copper ion before a reaction can occur. But measurements of the actual enzymatic rate gave a result that was faster than theoretically possible given the diffusion rates inside the cell.

It wasn't until the structure of the enzyme was solved that this mystery was cleared up. Look at the structure shown above. This is the human version of copper-zinc superoxide dismutase from 2003 [1HL5]. The structure is drawn in a way that highlights the charges on the surface of the enzyme. Red side chains are negatively charged and blue side chains are positively charged. The entry channel to the copper ion (green) at the active site is lined with positively charged amino acid residues. These suck in the negatively charged oxygen radicals like a vacuum cleaner and feed them to the active site. That's how the enzyme can operate so fast.

Do You Think Iran Will Get the Messsage?

 
Here's a scary report from the New York Daily News [ Bush eyes 'surgical' strikes vs. Iran, sez mag]. The Daily News article is based on an analysis by Seymour M. Hersh in the New Yorker magazine [Shifting Targets]. Hersh describes the increasing rhetoric about Iran's involvement in Iraq and the intelligence evidence that links Iran to the killing of American soldiers. This ties in with the growing realization that Iran is not about to develop nuclear weapons anytime soon. With that excuse gone, America needs another reason to justify the war against Iran. Here's how Hersh describes the situation ...

This summer, the White House, pushed by the office of Vice-President Dick Cheney, requested that the Joint Chiefs of Staff redraw long-standing plans for a possible attack on Iran, according to former officials and government consultants. The focus of the plans had been a broad bombing attack, with targets including Iran’s known and suspected nuclear facilities and other military and infrastructure sites. Now the emphasis is on “surgical” strikes on Revolutionary Guard Corps facilities in Tehran and elsewhere, which, the Administration claims, have been the source of attacks on Americans in Iraq. What had been presented primarily as a counter-proliferation mission has been reconceived as counterterrorism.

The shift in targeting reflects three developments. First, the President and his senior advisers have concluded that their campaign to convince the American public that Iran poses an imminent nuclear threat has failed (unlike a similar campaign before the Iraq war), and that as a result there is not enough popular support for a major bombing campaign. The second development is that the White House has come to terms, in private, with the general consensus of the American intelligence community that Iran is at least five years away from obtaining a bomb. And, finally, there has been a growing recognition in Washington and throughout the Middle East that Iran is emerging as the geopolitical winner of the war in Iraq.

It looks like the American people weren't buying the nuclear bomb spin so something new was needed. Who do you think is behind this new tactic? It's Dick Cheney, of course. Hersh quotes his unnamed source,

The former intelligence official added, “There is a desperate effort by Cheney et al. to bring military action to Iran as soon as possible. Meanwhile, the politicians are saying, ‘You can’t do it, because every Republican is going to be defeated, and we’re only one fact from going over the cliff in Iraq.’ But Cheney doesn’t give a rat’s ass about the Republican worries, and neither does the President.”

Judging from what I saw on television last week, the media is buying into the switch in tactics. Almost everyone who interviewed Ahmadinejad asked about "killing American soldiers in Iraq." Is it really this easy to trick the media? Doesn't anyone have the gumption to stand up to the propaganda machine and ask the hard questions?

Realistically, what do you expect Iran to do? There's a bloody civil war going on just across the river. It involves, among other things, religious groups with which Iran has some sympathy. In addition, Iraq is being occupied by 150,000 troops from a foreign country that labels Iran as a member of the axis of evil. It would be shocking if Iran didn't have people in Iraq with a view to influencing the outcome. I suspect Saudi Arabia and Kuwait are also sending "advisors" and supplies into Iraq.

The logic of the "surgical strike" tactic escapes me. Does the American administration really believe that Iran would roll over and play dead as soon as American bombers attacked supply bases in Iran? Isn't it likely that such an attack would galvanize Iranian public opinion leading to greater involvement in Iraq? Is it possible that some foreign nations like China or Russia would ship anti-aircraft missiles to Iran so it could defend itself? What if Iran retaliated by firing surface-to-sea missiles at the next aircraft carrier to pass through the Strait of Hormuz [Iran tests upgraded surface-to-sea missile]?

“They’re moving everybody to the Iran desk,” one recently retired C.I.A. official said. “They’re dragging in a lot of analysts and ramping up everything. It’s just like the fall of 2002”—the months before the invasion of Iraq, when the Iraqi Operations Group became the most important in the agency. He added, “The guys now running the Iranian program have limited direct experience with Iran. In the event of an attack, how will the Iranians react? They will react, and the Administration has not thought it all the way through.”

That theme was echoed by Zbigniew Brzezinski, the former national-security adviser, who said that he had heard discussions of the White House’s more limited bombing plans for Iran. Brzezinski said that Iran would likely react to an American attack “by intensifying the conflict in Iraq and also in Afghanistan, their neighbors, and that could draw in Pakistan. We will be stuck in a regional war for twenty years.”

Surely those who advise the American President can't be this stupid? You'd think they would have learned a thing or two from their previous mistakes in 2003, wouldn't you? This is a dangerous game. Expanding the war into Iran is not going to make America safer and it's not going to win any friends. America needs people like Zbigniew Brzezinski to speak up now. It's clear that you can't rely on Congress, just like you couldn't rely on it in October 2002 [Iranian Army Is a Terrorist Organization - What's This All About?].

The Price of Atheism

 
From an ABC 20/20 special on atheism in July 2007.

Billy Learns About Transposase

 

Monday's Molecule #45

 
There's no structure today. Instead, I've given you a photograph of a flower. Isn't it pretty?

You have to guess what molecule I'm thinking about, using the peculiar colored flower as a clue. It's the pattern of purple/pink stripes that gives it away. What molecule caused that pattern? There's a direct connection between this molecule and Wednesday's Nobel Laureate(s).

The reward goes to the person who correctly identifies the molecule and the Nobel Laureate(s). Previous free lunch winners are ineligible for one month from the time they first collected the prize. There are three ineligible candidates for this Wednesday's reward. The prize is a free lunch at the Faculty Club.

Send your guess to Sandwalk (sandwalk(at)bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the molecule and the Nobel Laureate(s). Correct responses will be posted tomorrow along with the time that the message was received on my server. This way I may select multiple winners if several people get it right.

Comments will be blocked for 24 hours. Comments are now open.

The Toronto Star Endorses First-Pass-the-Post

 


Today's editorial in The Toronto Star speaks against the mixed member proportional (MMP) electoral system and in favor of the status quo [Electoral reform a backward step].

The editors note that John Tory, the Progressive Conservative leader, is cool on the idea of MPP. The editors say,

Although the new system promises to deliver a legislature that mirrors the voters' intent, Tory notes it would also create two classes of members of the Legislature. Some would have a direct mandate from the voters; others could simply be appointed by party bosses.

If that is a democratic gain, it is hard to see.

Under the current system, nominees are appointed by a tiny number of dedicated people in each riding. Sometimes there are nomination meetings attended by a sizable crowd but those meetings are prone to stacking and all kinds of other abuses. The point is not that this is evil, the point is that the current system isn't as pristine as the first-past-the-post advocates claim.

The selection of party lists can be done in many different ways. It could be by party bosses in some dark room or it could be a much more open process. We don't know how it will work out under the new mixed member proportional system. I tend to think that a more open process will prevail since all of Ontario will be watching to see who's at the top of the list. In the case of the Green Party, for example, it will be interesting to see who the four new members will be if they pull 3% of the votes. It will certainly influence whether I cast a vote in their direction.

The same thing applies to all other parties. I won't be inclined to vote for a list of stooges, and you can be sure the other parties will be certain to point out the defects in party lists.

I think this argument against MMP is almost completely bogus. It's scaremongering and nothing more. One of the advantages of the MMP system, in my opinion, is the opportunity to get people into the legislature who might otherwise have little chance of getting elected. People who aren't wealthy enough to personally finance a campaign or a contested nomination, for example, or people who aren't good door-to-door campaigners but who would be an asset to Parliament. (Scientists, who aren't good at spinning framing sticking to the party line?)

The other argument used by the editors is more of the same whining we've heard dozens of times before.

Jurisdictions that have adopted some form or other of proportional representation – think of Italy, Israel, Germany, Belgium – have become notorious for chaotic politics and legislative gridlock.

While the occasional minority or coalition government beats the odds and performs well, far more commonly they are bitterly divisive, short-lived and paralyzed by conflict. Routinely, whoever heads the leading party is forced to cater to the demands of small, sometimes radical special-interest parties that enjoy no wide support, just to stay in power. That in itself is a distortion of the voters' will.

Let's get one thing straight, an inconvenient truth that's often ignored by all those who oppose MMP; as noted in the editorial, the last time a government of Ontario was elected by a clear majority was 70 yeas ago. Ever since then it's been the will of the people to cast their votes for a number of different parties such that no one party gets 50% of the votes. In other words, the people don't want majority governments. Nevertheless, majority governments are what the first-past-the-post system delivered in almost all elections. The Toronto Star editors are arguing that the real will of the people should be ignored in the interests of "stability." It's an argument that's often used against democracy.

No one suggests that first-past-the post is perfect. But Ontario's current system is democratic and robust, delivering strong, stable government that works. Why strain to "fix" what isn't broken?

If you're going to use this argument then please grant us the courtesy of explaining why you think "stability" should trump the clear preferences of the electorate and tell us just how far you're prepared to go in that direction.

There's no point in creating worse case scenarios in order to frighten people. I could just as easily bring up cases under first-past-the-post where a majority government, elected by less than 50% of the votes, thwarted the expressed will of the majority. "Stability" isn't always desirable at the expense of true democracy.

Yes, there are examples in foreign countries of legislatures that are gridlocked because the people want it that way. This happens under all kinds of electoral systems but it is more likely under true proportional systems and less likely under the mixed proportional system that we are considering. Will it happen in Ontario? I don't know, and neither do the editors. Personally, I think it's very unlikely given our history. It seems to me that there's very little chance that the government of Ontario would end up becoming beholding to a small party of four or five members.

Incidentally, all four of the countries mentioned (Italy, Belgium, Germany, Israel) are modern progressive countries with histories of social reforms that Canadians have emulated, or envied. The idea that nothing gets done in the legislatures of these countries does not stand up to close scrutiny.

---

[Photo Credit:Top: Police demonstrating how to maintain stability during the Queen's Park anti-poverty protest on June 15, 2000. Bottom: An example of the results produced by a first-past-the-post electoral system. "Thousands of teachers rallying at Queen's Park in the fall of 1997 were dismayed by government's lack of respect for the teaching profession." (Catholic Teachers Association) In 1995 Mike Harris' conservative government got 45% of the popular vote and 64% of the seats. In the 1999 election Mike Harris got 45% of the vote and 57% of the seats.]

Protein Secretion and Vesicle Traffic by Randy Schekman

 
Randy Schekman is a Professor at the University of California, Berkeley. He is one of the world's leading experts on sorting and secretion. The recent postings on The Signal Hypothesis and Signal Recognition particle focus on part of the sorting and secretion pathway. Schekman delivers three lectures on another part of this process, namely the formation of secretion vesicle in the cell and how they travel to the cell surface where they deliver their contents. The lectures are part of the iBioSeminars sponsored by The American Society for Cell Biology [Protein Secretion and Vesicle Traffic].

I think these lectures are examples of high quality science education unencumbered by any overt attempt to persuade the audience to adopt a particular social or political point of view.

---

[Hat Tip: Bertalan Meskó at ScienceRoll (iBioSeminars: Bringing the best in biological research to the world]

Big Ideas: Saturday September 29, 2007

 
Every weekend TV Ontario broadcasts talks given by prominent thinkers at lectures given in Toronto. The broadcasts are at 4pm Saturday, repeated at 4pm on Sunday. You can also watch them on the Big Ideas website. The host, Andrew Moodie (photo below), often has insightful comments so it's better to watch the actual TV broadcast than the website video presentations. While Moodie is good, he's not as good as the previous host, Irshad Manji, in my opinion.

Today's lecturers will be of interest to Sandwalk readers. University of Toronto students will be familiar with Sue Varmuza.

Mark Abrahams
Marc Abrahams, editor of The Annals of Improbable Research and one of the organizers of the annual Ig-Nobel Prize ceremonies at Harvard University, discusses the work of scientists and academics that, "first makes you laugh, and then makes you think". Highlights of the lecture include discussions of a study that proves that Kansas is flatter than a pancake and a paper investigating The Forces Required to Drag Sheep Over Various Surfaces.

Sue Varmuza
The second lecture in this episode of Big Ideas is by University of Toronto Zoology researcher Susannah Varmuza who discusses the evolving field of Epigenetics and what research into such things as mouse coat colour is telling scientists about the age-old "nature versus nurture" debate.

Here's the link: Susannah Varmusa.

MMP & Party Lists

 


I suppose it's to be expected. People who are opposed to the Mixed Member Proportional system are making up stories in order to make it seem as bad as possible.

There seems to be a lot of confusion about the party lists. Here's a brief summary from the Vote for MMP website.

Elections Ontario will publish the selection of candidates that each party has democratically elected before the election.

This information will be widely available in advance, as required by law:

• you'll know who party members selected before you vote for that party
• you'll know whether a party valued having a good balance of women and men
• you'll know whether a party valued having candidates from across the province, from rural and urban regions
• you'll know whether a party valued having candidates who reflected Ontario's diverse population
• you'll be able to decide before you vote whether a party created its list in a fair and democratic way

The important point here is that you will know who's on the list before you vote. You don't have to vote for the party if you don't like the list. Some people seem to think that a defeated candidate can be moved to the list after the votes have been counted and get elected by the back door.

Most people are worried about the party lists. They seem to think that the people on the list will be worthless party hacks. I don't think this is a major concern for two reasons.

1. Local ridings are already nominating worthless party hacks so the situation could hardly get any worse.
2. You won't vote for a party if their list is full of people who shouldn't be in the legislature.

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.

---

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. 

---

[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?

---

[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.

---

[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.

---

[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]