March 2005 Archives

Should I be Surprised?

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DeLay is a hypocrite. House Majority Leader, Tom “minorities took my spot in ‘Nam” Delay, the strongest advocate in Washington of keeping Terri Schiavo’s body alive, agreed to let his injured father die in 1988.

There were also these similarities: Both stricken patients were severely brain-damaged. Both were incapable of surviving without medical assistance. Both were said to have expressed a desire to be spared from being kept alive by artificial means. And neither of them had a living will.

I wonder where DeLay’s “culture of life” was in 1988.

(Via Blog for Democracy.)

HOTHEAD

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I finally went to the Arabidopsis database and looked up the HOTHEAD gene mentioned in my previous post. Here is the database’s information on the gene. The detailed annotation of the gene, describes what is known or predicted about it:

  • involved in cell-cell signaling (inferred from mutant phenotype)
  • located in extracellular region (inferred from sequence or structural similarity)
  • has mandelonitrile lyase activity (inferred from sequence or structural similarity)
  • functions in FAD binding (inferred from sequence or structural similarity)

The predicted mandelonitrile lyase activity suggests that the gene may catylse the reaction of mandelonitrile = cyanide + benzaldehyde. Here are some details of the enzyme from Black Cherry.

FUNCTION: Involved in cyanogenis, the release of HCN from injured tissues. Catalyzes the stereospecific addition of HCN to a variety of aldehydes in vitro. It is a major seed constituent, and could have the additional role of a storage form for reduced nitrogen. CATALYTIC ACTIVITY: Mandelonitrile = cyanide + benzaldehyde. COFACTOR: FAD

None of this seems to help me get a clear picture right now. Anybody got any idea?

A new paper by Susan Lolle, Robbert Pruitt, and collegues at Purdue Univeristy is making some press. The NY Times covered it in a story entitled, Startling Scientists, Plant Fixes Its Flawed Gene. Carl Zimmer has discussed it on his blog: Move Over, Mendel (But Don’t Move Too Far). The paper is entitled, “Genome-wide non-mendelian inheritance of extra-genomic information in Arabidopsis.” It was quickly published in Nature this week, and is now available as an advanced access publication. I think Nature in its rush to publish cutting edge science has (once again) published a paper of fantastic claims that could use a little more support. I will explain below.

In a 1998 paper, the two main author identified and studied the genes that are involved in organ fusion in Arabidopsis thaliana. They subsequently noticed that one of their genes, hothead (HTH/hth) showed an extremely high rate of reversion from null (hth) to wild-type (HTH). The rate of reversion for several different null alleles, 0.040 - 0.082, was very much higher than expected from typical mutation rates.

They initially suspected that their stocks had been contaminated with wild-type seeds or that their plants were out-crossing with wild-type pollen. However, they genotyped embryos and demonstrated the existence of revertant embryos, which ruled out seed contamination. They next ruled out pollen contamination by demonstrating that pollen from an hth/hth plant can transmit the HTH allele.

Sequencing ruled out the involvement of transposons and repeated sequences. They also tested whether the gene had a higher mutation rate but ruled it out due to lack of silent nucleotide substitutions. They ruled out gene conversion through non homologous recombination because they found no suitable donor sequence in the genome. They also found that molecular markers were genetically unstable (i.e. high mutation rate) in hth/hth plants but not in HTH/HTH plants. This argued for a genome wide effect.

With all these options investigated and ruled out, the authors proposed that genetic information was transmitted not only in the genome but in an additional way. This secondary information was then restoring the HTH allele in some hth/hth individuals. The researchers proposed (double-stranded) RNA as the possible vehicle for this secondary storage.

I think that Lolle et al. missed one important mechanism when they were considering possible explanations: selection. Before I continue, I want to point out what else I think is missing in the study: direct sequencing of male gametophytes to determine their haplotypes, some statistical tests, hth alleles not due to point mutations, knowledge of the rate of silent mutation rates for wild-type hothead genes, and probably a few other things.

I prefer selection over the explanation proposed by the authors, since it is a well established mechanism for changing allele frequencies and it can explain why the reversions only occur in pollen. The selection I’m proposing is the result of pollen competition; i.e. HTH pollen fertilizes ovules better than hth pollen. With pollen having a much larger population size than ovules, there is a greater chance at producing a revertant through mutation, at which point selection can act upon it. HTH could also be important for ovule success, but the lower population size of ovules and less chances for competition would make the effect less likely to show up.

What about the fact that genetic instability was found in other markers in hth/hth individuals? Well, I suspect that the loss of a functioning hothead gene increases the global mutation rate, which affects those markers too. Perhaps this is the reason why HTH pollen is selected for; it puts the mutation rate back in order.

Why didn’t the researchers find silent mutations in revertant HTH? Well, if the revertant HTH is selected because it fixes mutation rates, then individuals that revert sooner than later may be preferred. The fastest way to produce revertant HTH is to reverse the point mutation that produced hth. The researchers might not have had the power to detect silent mutations in revertant HTH because they only sequenced three lines.

What about the fact that HTH/hth heterozygotes produce hth/hth individuals at nearly 25%? Doesn’t that exclude pollen selection? Well, the advantage of HTH pollen over hth pollen may be a paternally influenced trait that only shows up from hth/hth pollen donors. The advantage may also be frequency dependent and only occur when HTH is rare.

The paper by Lolle et al. involves a really interesting system, but I seriously doubt that their proposed explanation will hold up. I think selection, which isn’t discounted by their results, is a better explanation. It is really going to be interesting as more papers and other labs try to figure out what is going on in this system.

References

  • Lolle SJ et al. (2005) Nature 434: 505-509.
  • Lolle SJ et al. (1998) Genetics 149: 607-619.

Second Paper

Well I submitted a short application note tonight to Bioinformatics. Douglas Theobald and I developed a new method for translation coding sequences.

I am now polishing off another, larger paper.

Spore

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This might be a computer game of interest to you biology buffs. Will Wright, creator of Sim (anything), recently presented a new project: Spore. The impetus behind the game is that users should be able to design the content and share it online with other users.

The game starts out humbly enough, with little microorganisms slurping around a puddle of green goo. Wright led his tiny microscopic creature around, eating little green cells and avoiding brown cells or black cells that tried to eat him. “This is kinda like Pac-Man,” he explained. After he ate enough, he was rewarded with the ability to lay an egg – which he did.

Clicking on the egg brought up a creature editor, and allowed the player to “evolve” with a new generation of critters. The editor was amazingly flexible. Wright could give his creature extra vertebrae, he could give it fins or tails to move faster, he could add claws or extra mouths, whatever he wanted. More importantly, all the creature animations weren’t hard-coded; they were dynamic. If he put six tails on his creature, the game would figure out how a six-tailed creature would move. The critter was completely his.

The game goes much farther, but I won’t say anymore, or I’ll ruin the surprise.

Congressional Power Grab

CBS News has a very good article on Congress’s decision to interfere with Terri and Michael Schiavo’s family business. I agree with everything the commentator said. This is a horrible attempt at trial by legislation. The law is entirely constitutionally and morally suspect in that it only applies to Terri Schiavo and only for thirty days. Above that it usurps state power and completely violates separation of powers.

A leaked memo proves that the Republicans are doing this for political reasons and not any concern for the Schiavo family. I think the Senate knew exactly what it was doing when it defied the House and wrote its own law. The Senate wrote a law that is obviously unconstitutional, establishes no new law, and is going to get tossed out by the courts. That way they can appeal to the Religious Right while not doing anything at all.

I really hope that the federal court doesn’t delay and tosses this law out as soon as it can. After all, they don’t have to worry about election.

Schiavo Brain Scans

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Ignore my crappy figures in the post below. Through PZ, I found actual CT scans of Schiavo’s brain.

There is also commentary on Alas, a blog about them.

Terri Schiavo’s Body

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I’ve been paying attention to the legal fight over Terri Schiavo’s body for the last few years. I am really disgusted by how the authoritarians of the religious right and Republican Party have violated the nature of family. Michael Schiavo as Terri’s husband is her next-of-kin and thus has authority over her medical treatment. Neither her parents nor the politicians who support them have any business to usurp his judgment or interfere in his family business. Don’t people realize that if politicians can pass laws to block feeding tube removal, then they can pass laws requiring it? Do they really want politicians deciding who lives and who dies?

People are upset over Michael Schiavo’s judgment, but they rarely know what his judgment actually was. Michael Schiavo’s judgment is that his wife is gone and is not coming back. He knew that his wife would not want her body unnaturally sustained in its current condition. In 1998 he petitioned the court to determine whether the feeding tube for Terri’s body should be removed. After hearing evidence from both sides, the judge agreed with the judgment of Terri Schiavo’s husband.

It is disturbing to follow the discussions about Terri Schiavo that occur on Baptist Board because they are so completely void of informed opinions.

They think that her husband is doing this for money. Not only is there little money left, but he has turned away people, who have tried to buy Terri from him for millions of dollars.

They think that Michael Schiavo beat his wife into her condition and is trying to take her off life support to cover up his crime. Her condition was caused by an electrolyte imbalance resulting from bulimia.

They hate the judge for not being activist. Yet his conclusion is not only completely consistent with Florida Law but the traditions of our nation.

These people actually believe that Terri is awake and responds to her parents. The judge reviewed all the video tapes of Terri’s behavior, not just the ones available on her parents’ website, and found her responses as inconsistent.

They believe that starvation is a cruel way to die. Studies reveal that it is the most humane and peaceful form of euthanasia. After a few days hunger subsides, and endorphins are released by the body, which block pain.

These people actually believe that Terri is aware and still exists as a person. Her upper brain (cerebral cortex) died years ago and no longer exists. The upper brain is what processes our senses, forms our conscience, and makes us who we are. I wonder how many people on Baptist Board would form a different opinion of this issue if they saw these two figures:

A normal brain:

A brain without the cerebral cortex (like Terri Schiavo’s):

That’s a pretty powerful pair of figures in my opinion.

Going Home

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Yesterday, I took Tiffany out to the neighborhood where I grew up. I wanted to show her some of the cool places where she could hide a letterbox. I showed her the ponds and the park. A creek runs alongside the ponds, and we walked in the woods along the creek down to the waterfall and back. Large pine trees had fallen all over the woods, perhaps from a pine beetle infestation.

The neighborhood has changed a lot in recent years. A middle school was built across the street from it, leading to new development, and lots that were once wooded now have new houses on them. Someone has actually built a house right next to the home of my childhood. I don’t like it.

My dad still owns the house I grew up in and my brother lives there now. The house is probably thirty years old and hasn’t had someone keeping it up in the last ten years or so. It needs to be renovated, but my dad doesn’t care and my brother can’t afford to do it. It really saddens me. I love that house; it has so many neat features. My dad actually built the neighborhood and situated the house on top of a hill over the upper pond. It really is a beautiful place. I would love to see it renovated to fix it faults. Thinking about that house made me realize that I’m never going to have a house as good as that one.

Presentation Finished

Well, I gave my talk this morning, and it went smoothly. I had a few questions, and a few people made sure they had the correct address of the software. Here is my presentation if any of you are interested.

SEEC 2005

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I get to give my first scientific presentation at a scientific conference this weekend. I will be presenting my sequence simulation program, Dawg, at SEEC (Southeastern Ecology and Evolution Conference). I still have to put the presentation together and practice it. I do have a longer presentation to work from.

The University of Georgia’s Carl Vinson Institute of Government regularly conducts polls from around the state. This week’s poll is on evolution and is not as scary as I first thought.

Georgians generally are opposed to teaching evolution as the sole explanation for the origins of our species. Less than one in five Georgians (17 percent) believe that public schools should teach evolution to the exclusion of other theories not broadly adopted by the scientific community. A slim majority (54 percent) feels that religious theories should be included in the classroom, and almost one in four (23 percent) believes that the schools should not teach evolution at all.

The poll also found that older people, those without college degrees, those outside the metro-Atlanta area, and Republicans most opposed the teaching of evolution. This is not what bothered me. I was bother by the fact that so few Georgians (17%) think that non-scientific ideas should not be taught in science education. However looking at the full report, I found that the press release was misleading. The phrase “to the exclusion of other theories not broadly adopted by the scientific community” was not contained in the question asked by the Institute. The actual question was

Do you think Georgia public schools should teach only evolution as the explanation of the origin of humans, should teach evolution as well as religious explanations of the origin of humans, or not teach evolution at all?

It seems that the Institute in their press release assumed information not contained in the question. The full report also contains the following note:

The Winter 2005 Peach State Poll had only a single item on the topic of teaching evolution; thus, we lack sufficient data to explore public attitudes on the issue at the time of this report. The survey item used was intended to measure the degree to which the public thought that evolution should be the sole theory explaining the origin of humankind taught in Georgia public schools. It should neither be taken as a measure of belief in evolution as the true explanation of man’s origin nor as support for the teaching of any other specific theory or belief such as intelligent design.

However, I doubt such omissions will stop the wedge pundits.

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