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Wednesday, March 05, 2014

The crystal structure of E. coli RNA polymearse σ70 holoenzyme

THEME:
Transcription

The Journal of Biological Chemistry (JBC) publishes a little booklet of the "best of jbc." The latest copy arrived in the mail a few days ago and it alerted me to a paper published one year ago on the structure of Escherichia coli RNA polymerase σ70 holoenzyme (Murikami, 2013).1

The control of transcription initiation is a very important topic in biochemistry and molecular biology and the events in E. coli are the model for transcription initiation in all other species. We know more about RNA polymerase and promoter sites in E. coli than in any other species.

Monday, March 03, 2014

Monday's Molecule #231

Monday's Molecule #230 (Jan. 27, 2014) [Monday's Molecule #230] was 2-carboxy-3-ketoarabinitol 1,5-bisphosphate. It's an intermediate in the reaction catalyzed by ribulose 1,5-bisphosphate carboxylase-osygenase (Rubisco), the key enzyme in the Carvin cycle. This is the molecule created by adding CO2 to the 2-carbon atom of ribulose 1,5-bisphosphate. The winners were Bill Gunn closely followed by the first correct answer from an undergraduate, Ariel Gershon. Ariel is a student at the University of Toronto so it looks like I'm going to have to buy a lunch.

This week's molecule (below) is a sequence. Name the sequence in red and briefly describe it's function.
Email your answer to me at: Monday's Molecule #231. I'll hold off posting your answers for at least 24 hours. The first one with the correct answer wins. I will only post the names of people with mostly correct answers to avoid embarrassment. The winner will be treated to a free lunch.

There could be two winners. If the first correct answer isn't from an undergraduate student then I'll select a second winner from those undergraduates who post the correct answer. You will need to identify yourself as an undergraduate in order to win. (Put "undergraduate" at the bottom of your email message.)

Carnival of Evolution #69

This month's Carnival of Evolution is hosted by a BIOCHEMIST (yeah!) named "Lab Rat" (S.E. Gould) at Lab Rat. Read it at 69th Carnival of Evolution: Darwin’s Day Edition.
Welcome to the 69th edition of the Carnival of Evolution! As February 12th was Darwin’s birthday, this is a Darwin’s Day carnival edition. To start with there’s a celebration of all things Darwinian at Synthetic Daisies, and a letter to the man himself for his 205th birthday.
The next Carnival of Evolution will be at ????

If you want to host a Carnival of Evolution please contact Bjørn Østman. Bjørn is always looking for someone to host the Carnival of Evolution. He would prefer someone who has not hosted before but repeat hosts are more than welcome right now! Bjørn is threatening to name YOU as host even if you don't volunteer! Contact him at the Carnival of Evolution blog. You can send articles directly to him or you can submit your articles at Carnival of Evolution although you now have to register to post a submission. Please alert Bjørn or the upcoming host if you see an article that should be included in next month's. You don't have to be the author to nominate a post.

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Carnival of Evolution #68

I forgot to post a link to last month's Carnival of Evolution. It was hosted by a computational biologist who posts at Byte Size Biology. Read it at Carnival of Evolution, February 2014 Edition.
Wow, I haven’t posted anything in quite a while. Things are busy outside blogoland. But committing this blog to the February edition of the Carnival of Evolution just made me do it, so here goes. We’ll do this by scales, bottom up.
The next Carnival of Evolution (#70, April, 2014) will be at some unknown place.

If you want to host a Carnival of Evolution please contact Bjørn Østman. Bjørn is always looking for someone to host the Carnival of Evolution. He would prefer someone who has not hosted before but repeat hosts are more than welcome right now! Bjørn is threatening to name YOU as host even if you don't volunteer! Contact him at the Carnival of Evolution blog. You can send articles directly to him or you can submit your articles at Carnival of Evolution although you now have to register to post a submission. Please alert Bjørn or the upcoming host if you see an article that should be included in next month's. You don't have to be the author to nominate a post.

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Death of the genome paper

There was a time when sequencing a gene was just about all you needed to get a publication. Getting a high quality sequence of a typical protein-encoding gene (cDNA) took several years of work—almost sufficient for a Ph.D. thesis.

By the 1990's, that was routine and you needed much more to get a paper published. The genome era had begun and a good paper in a high impact journal required the complete sequence of an entire genome.

Today, you can't get a genome sequence published because it's so easy that undergraduates can do it.

David Smith of Western University (London, Ontario, Canada) laments the death of the genome paper while recognizing that sequencing has probably been abused (Smith, 2013). He makes some good points ...
One of the drawbacks of genome papers, however, is that they can create a mindset of sequence first, ask questions later. I once attended a Masters thesis defense where the external examiner asked the candidate why he sequenced the chloroplast genome of this particular species and what hypothesis was he trying to test. The student, looking startled, answered, "Because the genome hadn't been sequenced before and we didn't know what it looked like." After the defense, I overheard the examiner in the hallway venting to another professor. "We've created a culture of serial genomicists," she exclaimed. "Everyone's jumping from one genome sequence to the next, looking to score a major publication."

Regardless of this opinion, genome papers have provided much of the raw data that have shaped our view of genetics and evolution over the past 20 years. And they can also be a joy to read. Many of my favorite journal articles are genome papers. I remember, when I was a grad student in phycology, eagerly awaiting publication of the genome for Chlamydomonas—the superstar of green algae—and reading it incessantly once it was released, gleaning new insights each time through. There is something intimate and personal in learning about a species' genome. And similarly, if you are part of the team describing the genome, there is a feeling that you're giving the readers a first glimpse at an uncharted territory, with its unique landscape of genes, introns and intergenic regions.

But all of this may be coming to an end. Next generation DNA sequencing techniques have made it easy, fast and cheap to sequence genomes. Today, just about any scientist can walk out their laboratory doors, point to a living thing and say, “I will sequence you!” High-throughput technologies have flooded the academic market with genome papers. And the top journals have responded by only accepting papers describing the most novel, earth-shattering genomes. The less spectacular genomes, much like B-movies, go directly to video, or rather directly to GenBank. This sequencing-vs-publishing arms race has been going on for a long time.

...

Is it time to write the genome paper obituary? Maybe not quite yet. Every now and then they still claw their way into top journals. But the end is not far off, and when it does come, I'm sure that I speak for all of us genome geeks when I say, "Farewell, GP. It was fun while it lasted."
I still like to read genome papers but lately I've been put off by the lack of reliable information in most of those papers. One of things I'm interested in is the number genes, especially the number of unique genes. Unfortunately, the annotation usually relies on computer-generated gene predictions and those are notoriously unreliable.


Smith, D.R. (2013) Death of the genome paper. Frontiers in Genetics 4:1-2. [doi: 10.3389/fgene.2013.00072]

Friday, February 28, 2014

Why are the human and chimpanzee/bonobo genomes so similar?

David Klinghoffer isn't impressed by the fact that the DNA of humans and bonobos is 98.6% identical in the areas that can be aligned. Here's what he says at: This Might Be the World's Most Underwhelming Evidence for Darwinian Evolution ...
Oh please. If there are any "creationists" out there who are running scared, they need not do so. The new article [by Chris Mooney] is titled "You Share 98.7 Percent of Your DNA with This Sex-Obsessed Ape," referring, of course, to the precious bonobo, a chimp-like ape famous for its progressive sexual habits. Just by itself, the genetic similarity between us and apes such as the bonobo is supposed to be of knockdown importance.

But what else would anyone expect, whether on a model of Darwinism, intelligent design, or creationism? Apes and humans are similar in many ways, and you don't need Darwinian evolution to see this.
This is a common argument from the IDiots. They assume that the intelligent designer created a model primate and then tweaked it a little bit to give chimps, humans, orangutans, etc. That's why the genomes of these species are so similar.

Unfortunately for them, there's a bit more to it than that. Their model of intelligent design also has to account for the fact that humans are more similar to chimps/bonobos than to gorillas and all three are about the same genetic distance from orangutans. This sequence data correlates with the fossil record over a period of about 10-15 million years.

It gets even worse for the IDiots. Evolutionary theory predicts that the rate of change should correspond to the mutation rate since most of the differences are due to neutral substitutions in junk DNA. We know that the mutation rate is about 130 mutations per generation based on our knowledge of biochemistry. This rate has been confirmed by direct sequencing of parents and children [Estimating the Human Mutation Rate: Biochemical Method] [Estimating the Human Mutation Rate: Direct Method].

If evolutionary theory (population genetics) is correct, and if David Klinhoffer and chimps/bonobos actually evolved from a common ancestor, then we should observe a correspondence between the percent similarity of Klinghoffer and chimps and the predicted number of changes due to evolution.

Let's see if it works.

The human and chimp genomes are 98.6% identical or 1.4% different. That difference amounts to 44.8 million base pairs distributed throughout the entire genome. If this difference is due to evolution then it means that 22.4 million mutations have become fixed in each lineage (humans and chimp) since they diverged about five million years ago.

The average generation time of chimps and humans is 27.5 years. Thus, there have been 185,200 generations since they last shared a common ancestor if the time of divergence is accurate. (It's based on the fossil record.) This corresponds to a substitution rate (fixation) of 121 mutations per generation and that's very close to the mutation rate as predicted by evolutionary theory.

Now, I suppose that this could be just an amazing coincidence. Maybe it's a fluke that the intelligent designer introduced just the right number of changes to make it look like evolution was responsible. Or maybe the IDiots have a good explanation that they haven't revealed?

Or maybe they're just IDiots who don't know what they are talking about.


Thursday, February 27, 2014

Physicians and engineers are not scientists

Creationists are fond of mentioning people who are committed to creationism but still function as successful scientists. We saw an example in the debate between Bill Nye and Ken Ham. These creationist "scientists" are often physicians or engineers.

It seems obvious to most of us that engineers and physicians are not scientists. PZ Myers mentions this on his blog when he discusses the debate as reviewed by William Saletan: Saletan is at it again. Here's what PZ says ...
Engineers can practice real science, but an engineer is not the same thing as a scientist. I agree that creationists can be perfectly good engineers, but how can you trust the scientific acumen of someone who insists that the earth is only 6,000 years old? That says right there that they have no respect for the evidence. How can Saletan ignore Ham’s bogus distinction between historical and observational science, in which he flatly rejects any possibility of inference about the past from the present? This creationism is utterly incompatible with biology, anthropology, geology, astronomy, climate science, geochemistry, cosmology, and any other science that deals with cause and effect and history. These sciences apparently do not matter to Saletan, as long as engineers make satellites and doctors do surgery.

Saletan cites Ham’s videos as falsifying the claim that creationism is incompatible with science. Ken Ham makes a big deal of this, too.
This would be unremarkable except that Jason Rosenhouse disagrees [Saletan vs. Myers on Nye vs. Ham]. Here's what Jason says ...
Oh for heaven’s sake! Engineers are scientists. Full stop. Are you really that desperate to deny that a creationist could ever make a contribution to science that you will sink to this level of insult and idiocy? (Yes, it is insulting to suggest that engineers are not scientists.)
Engineers have a Bachelor's degree in engineering and they typically work for a construction company or in the IT department of a large corporation. They are not scientists. Full stop.

It's true that some engineers do science but usually they have a higher degree in engineering and usually they are academics. There's no possible way you could assume that all engineers are scientists just because they are licensed engineers and wear the ring. I'm sorry, Jason, but you are wrong.

Similarly, the typical physician has a private practice at a strip mall in the suburbs. They have an M.D. degree that can be earned right out of high school (in Europe). They are not scientists.

There are some physicians who are scientists and some of them have earned Nobel Prizes. They are the exceptions, not the rule. It's ridiculous to assume that everyone with an M.D. is a scientist.


A mind like that is a disgrace to the human species

Here's a five year old video where Richard Dawkins points to molecular phylogenies as powerful evidence of evolution. He wonders how any creationist could deny the evidence of evolution and suggest that "a mind like that is a disgrace to the human species."

He must have been thinking about Cornelius Hunter because Hunter has resurrected the video in order to show why Dawkins is wrong [Richard Dawkins: How Could Anyone "Possibly Doubt the Fact of Evolution"]. Watch the video and then read what Cornelius Hunter says. You'll recognize some elements of truth in his criticism but you'll also recognize a common creationist fallacy; namely, an inability to see the forest because you've been staring too long at the bark on trees.



What is amazing is the evolutionist’s high confidence and self-assuredness in such a blatant misrepresentation of science. It would be difficult to imagine a bigger falsehood. Phylogenetic incongruence is rampant in evolutionary studies. Conflicts exist at all levels of the evolutionary tree and throughout both morphological and molecular traits. This paper reports on incongruent gene trees in bats. That is one example of many. These incongruences are caused by just about every kind of contradiction possible. Molecular sequences in one or a few species may be out of place amongst similar species. Or sequences in distant species may be strangely similar. As one paper admitted, there is “no known mechanism or function that would account for this level of conservation at the observed evolutionary distances.” Or as another evolutionist admitted, the many examples of nearly identical molecular sequences of totally unrelated animals are “astonishing.”

An even more severe problem is that in many cases no comparison is even possible. The molecular sequence is found in one species but not its neighbors. When this problem first became apparent evolutionists thought it would be resolved as the genomes of more species were decoded. No such luck—the problem just became worse. Not surprisingly evolutionists carefully prefilter their data. As one paper explained, “data are routinely filtered in order to satisfy stringent criteria so as to eliminate the possibility of incongruence.”

Short genes that produce what are known as microRNA also contradict Dawkins’ high claim. In fact one evolutionist, who has studied thousands of microRNA genes, explained that he has not found “a single example that would support the traditional tree.” It is, another evolutionist admitted, “a very serious incongruence.”

Another paper admits that “the more molecular data is analysed, the more difficult it is to interpret straightforwardly the evolutionary histories of those molecules.”

And yet in public presentations of their theory, evolutionists present a very different story. As Dawkins explained, gene comparisons “fall in a perfect hierarchy, a perfect family tree.” This statement is so false it isn’t even wrong—it is absurd. And then Dawkins chastises anyone who “could possibly doubt the fact of evolution.” Unfortunately this sentiment is typical. Evolutionists have no credibility.


On the absurdity of an atheist using the argument from evil

Gary Gutting interviews atheist Louise Antony in the New York Times [Arguments Against God]. Here's part of the interview ...
L.A.: Knowledge in the real world does not entail either certainty or infallibility. When I claim to know that there is no God, I mean that the question is settled to my satisfaction. I don’t have any doubts. I don’t say that I’m agnostic, because I disagree with those who say it’s not possible to know whether or not God exists. I think it’s possible to know. And I think the balance of evidence and argument has a definite tilt.

G.G.: What sort of evidence do you have in mind?

L.A.: I find the "argument from evil" overwhelming — that is, I think the probability that the world we experience was designed by an omnipotent and benevolent being is a zillion times lower than that it is the product of mindless natural laws acting on mindless matter. (There are minds in the universe, but they’re all finite and material.)
The argument from evil goes like this ...
  1. Assume that supernatural, omnipotent beings exist.
  2. Assume that they are kind and benevolent and they have the power and desire to create human societies that will be kind and good.
  3. Therefore, because evil is commonplace, one of the assumptions must be wrong.
An atheist is concerned about whether supernatural beings exist so why in the world would they pay any attention to the premises of this argument? If I were to accept the premise that supernatural omnipotent beings exist then the argument from evil simply leads to the conclusion that the supernatural beings are evil (like Satan) or they don't much care about us, like the Greek gods.

The argument from evil says nothing about whether gods exist or not. It only refers to particular kinds of gods and the only way an atheist should pay any attention to it at all is if they are willing to concede that some sort of gods must exist. Then, and only then, can they enter into a discussion about what kinds of gods exist. In that sense, the argument from evil is about as useful as the Courtier's Reply.

I wish atheists would stop discussing the argument from evil because all it does is show that some gods are possible while others are unlikely. I do not see why Louise Anthony finds the argument convincing because it's perfectly consistent with the existence of Satan.

It's also perfectly consistent the god of the Old Testament (see above). That god is exactly the sort of god that that would create a human society full of evil. Humans are behaving just like the god they worship. What's the problem?


Wednesday, February 26, 2014

Why the creationists love the 1980 Chicago meeting on macroevolution

A meeting on macroevolution was held at the Field Museum of Natural History in Chicago in October 1980. Normally these meetings would not attract much attention from the press but in this case there was an article published in Discover a month before the meeting took place that suggested something revolutionary was in the wind. Stephen Jay Gould discusses the episode in The Structure of Evolutionary Theory (pp. 981-986).

The article in Discover referred to "growing dissent from the prevailing view of Darwinism" and mentioned that there would be a meeting in Chicago. As a result of this article, a bunch of journalists turned up at the Chicago Macroevolution meeting expecting fireworks.

There was a lot of talk about punctuated equilibria at the Chicago meeting and how the ideas of Eldredge and Gould conflicted with the gradualism that was part of traditional Darwinian evolution. This is complicated stuff so it's no wonder that many journalists misinterpreted the discussion as support for the idea that evolution was being challenged as the creationists claimed.

Tuesday, February 25, 2014

My molecular evolution midterm test

My students wrote the midterm test today. Here are the questions. They had to answer the first question and 4 other questions (out of 5). How would you do?
  1. What’s the most important new thing about molecular evolution that you have learned in this course so far? Explain your answer by describing your "important new thing."
  2. If mutation rates are relatively constant then why does the molecular clock tick at different rates in different proteins?
  3. Many evolutionary biologists think that population genetics is the key concept in understanding evolution but biology students often complete several years of courses without ever learning about effective population sizes, mutation rates and the importance of random genetic drift. Why? Is it because population genetics is not a necessary key concept in evolution?
  4. Grad students at this university publish a journal called Hypothesis. A few years ago (2005) there was a student who wrote ...
    I am a grad student, and long hours at the bench have got me thinking of other things lately, including the idea of marriage. I came up with a few criteria to direct me on my quest for a wife, and near the top of the list was that she needs to know what a gene is. I thought that this would be a reasonable thing to ask for. I like learning about how we and the rest of life work, and knowing how, in a general sense, cells are programmed to do what they do is a pretty good indicator of similar interest. My friends, however, disagreed with me, and on several occasions, as I shared my list, I feared that things were going to get violent. They argued that I will never get married with such a short-sighted and elitist attitude.
    Imagine that you would only seek partners who knew what a gene was. What definition would you require and why?
  5. What’s the best evidence that a substantial amount of our genome is junk?
  6. Imagine that you are teaching a class and you ask students to calculate a mutation rate in humans based on what they know about biochemistry. What mistakes are they most likely to make and why?

Saturday, February 22, 2014

On moral absolutes and ethical relativism

Last week I commented on whether bigots should be given permission to discriminate against gays just because the bigots belong to a religion that promotes bigotry [The Kansas anti-gay bill]. My opinion is that societies should not tolerate bigotry no matter what motivates people to discriminate. I said ...
I read some newspaper articles, and some blog posts, that stated the obvious. It is totally wrong, all the time, to discriminate against someone based on their sexual preferences. If they use religion as an excuse then they should re-evaluate their religion. There is NEVER a time when an enlightened society should tolerate, let alone legalize, bigotry. I guess it's almost impossible to come out and say this on television, or maybe I'm just watching the wrong channels (mostly FOX and CNN).
What I mean is that enlightened societies will almost always reach a consensus on discrimination against minorities. They will decide that society functions best when all types of discrimination are bad and should not be tolerated.

Sunday, February 16, 2014

The Kansas anti-gay bill

I'm currently in Los Angeles visiting the grandchildren so I'm a bit more exposed to American culture than normal. I watched several discussions on the Kansas anti-gay bill on television and one thing struck me as highly unusual.

For the sake of non-Americans, let's begin with a description of the bill passed by the Kansas House, which is dominated by Republicans. Here's what Bill 2453 says ...
Notwithstanding any other provision of law, no individual or religious entity shall be required by any governmental entity to do any of the following, if it would be contrary to the sincerely held religious beliefs of the individual or religious entity regarding sex or gender: (a) Provide any services, accommodations, advantages, facilities, goods, or privileges; provide counseling, adoption, foster care and other social services; or provide employment or employment benefits, related to, or related to the celebration of, any marriage, domestic partnership, civil union or similar arrangement; (b) solemnize any marriage, domestic partnership, civil union or similar arrangement; or (c) treat any marriage, domestic partnership, civil union or similar arrangement as valid.
In other words, if you are a bigot then the state will protect you from prosecution as long as you claim that your bigotry is based on religion.

The bill was expected to pass through the Kansas Senate and signed into law by a redneck governor. Fortunately for Kansas, the Republican-dominated senate decided that Kansas should drop out of the competition for most stupid state and they declined to pass the bill [Kansas Senate Comes To It’s Senses And Nixes Extreme Anti-Gay Legislation ].

That's not what I want to talk about. What I witnessed on the American TV channels was a debate over the legality of discrimination of gays. The discussion hinged on whether it was legal for an anti-gay bigot to refuse to serve a gay couple in a restaurant or whether an anti-gay bigot could refuse to bake a wedding cake for a gay couple. Almost everyone I saw on TV agreed that it was perfectly okay for Americans to be anti-gay bigots, especially if their bigotry was related to their belief in God. The only serious question seemed to be whether there were legitimate times when anti-gay bigots could express their bigotry in public.

I read some newspaper articles, and some blog posts, that stated the obvious. It is totally wrong, all the time, to discriminate against someone based on their sexual preferences. If they use religion as an excuse then they should re-evaluate their religion. There is NEVER a time when an enlightened society should tolerate, let alone legalize, bigotry. I guess it's almost impossible to come out and say this on television, or maybe I'm just watching the wrong channels (mostly FOX and CNN).

I'm reminded of a statement by Winston Churchill about Russia; "Russia is a riddle wrapped in a mystery inside an enigma." That's the way I feel about the United States. There's such a huge difference between Boston and Texas that I wonder how they can both continue to exist in the same country.


A Darwin Day rap video

An old high school friend of Ms Sandwalk sent me the link to this video by Dirk Murray "Baba" Brinkman, Jr. He is the son of my friend's local MP, Joyce Murray (Liberal, British Columbia).

I hesitated to post in on Darwin Day but now that other blogs have linked to it, I want to use this opportunity to raise two important questions.
  1. The video promotes "Darwinism" as the only solution to evolution. This is wrong, but is there value in lying about this for a greater cause? Is it possible to make an effective video like this without distorting the science?
  2. I'm very uneasy about promoting Darwin worship, partly for the reason that there's more to evolution than what Darwin wrote in 1859 and partly for the reason that it smacks of religion. What do you think? Should we be pushing "Darwin Day"?
M=