25 Influential Atheists

 
Here's a list of The 25 Most Influential Living Atheists. How many do you recognize? Are they good people or are they all morally degenerate because they're not scared of God?

Why isn't Hemant Mehta on the list?

Here's a better list 'cause it includes some people who are much more interesting than Daniel Dennett [The 50 Most Brilliant Atheists of All Time].

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A Challenge to Fans of Alternative Splicing

There are many well-known examples of alternative splicing. These examples have been taught in undergraduate courses for 30 years and they are prominently featured in textbooks. Alternative splicing exists.

Here's the problem. The explosion of EST data in the 1990's resulted in detection of many sequences suggesting that alternative splicing was much more widespread that previously suspected. The vast majority of these claims have not been verified and many of them have been removed from the annotated genomes published in the past few years.

Now we have a whole new set of claims based on high throughput analysis of transcripts from a variety of organisms and tissues. Many workers believe that the majority of human genes are alternatively spliced and some even publish articles stating that 95% of humans genes exhibit alternative splicing. One of my colleagues who makes such a claim says that just because a gene is alternatively spliced doesn't mean that the various isoforms of RNA are functional but I think that's disingenuous. If it's going to be a meaningful term then "alternative splicing" has to imply that that at least two different versions of RNA have some biological function.

I've asked repeatedly for evidence that some particular genes are alternatively spliced to give rise to two or more functional products. It should be possible to get this information from the databases used by these researchers—the ones that support their claim of widespread alternative splicing. Unfortunately, this has proven to be difficult. Whenever I search common alternative splicing databases I'm told that those databases aren't very good and the results aren't reliable.

Here's the challenge to all researchers who believe that a majority of human genes are alternatively spliced (in a biologically relevant manner). Show me your data. Pick one of the following sets of genes and demonstrate that most of them have functional alternatively spliced transcripts. If none of the genes in the set qualifies then explain why you reject the presumed alternative transcripts shown in popular databases. This shouldn't be much of a challenge if your claim is correct.

Note that this is a two part challenge. You have to first present evidence that there are functional alternative splicing events and then you also have to present the reasons why you reject some of the data from sequenced RNAs.

Here's an example from the human gene for triose phosphate isomerase (TPI1). The Entrez Gene entry is Gene ID: 7167. The primary entry shows one alternatively spliced transcript that removes the N-terminal coding region of the protein and creates an new larger N-terminal sequence. What is the evidence that this is biologically relevant? Now check out the known transcripts that have been detected according to UCSC Genome Browser, AceView, and Model Maker. These show additional variants affecting the splice junction sequences around exons 2, 4, and 6. Are these also examples of alternative splicing? Are they functional? If you reject these variants then what's the rationale for accepting some possible transcripts as real but rejecting others? Are some of them artifacts?

The three gene sets are ...

1. Human genes for the enzymes of glycolysis.
2. Human genes for the subunits of RNA polymerase with an emphasis on the large conserved subunits [Two Examples of Alternative Splicing]
3. Human genes for ribosomal proteins.

I selected these examples because we know the structures of the proteins so we can evaluate the possibility that an alternatively spliced message might produce a novel polypeptide chain. Of course there might be other reasons (regulation?) for producing alternatively spliced transcripts. Feel free to present the evidence.

Now it's possible that I've accidentally chosen sets of genes that do not exhibit alternative splicing. If that's the case then pick any other set of genes with a common function where the structure of the protein product is known. Meanwhile, you can explain why you reject all the putative splice variants for these genes.

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What Does San Marco Basilica Have to do with Evolution?

Everyone interested in evolution should read the famous critique of the adaptationist program by Stephen Jay Gould (1941-2002) and Richard Lewontin (1929 - ). Whether you agree with them or not, it's essential that you become informed about the adpatationist-pluralist controversy—also known as the neutral-selectionist controversy. That controversy is still very much a part of the debates over evolution, although the adaptationist side tends to argue that the controversy has been settled.

It's no secret that I'm a huge fan of Gould and if I had my druthers I'd make students read every one of his books, including, The Structure of Evolutionary Theory. I'm a pluralist.

My friend John Wilkins, a philosopher, visited St. Mark's Square and the Basilica last year. He's on the opposite side of this debate and he offers the best defense of adaptationism that I've seen in recent years. You should keep an eye on his blog, Evolving Thoughts, it's a must-read for anyone who's serious about evolution. I blogged about John's version of adaptationism [An Adaptationist in Piazza San Marco].

This is a rich topic for undergraduates and there are many potential essay topics.

Michael Ruse Defends Adaptationism
Richard Dawkins' View of Random Genetic Drift
Naked Adaptationism

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Gould, S.J. and Lewontin, R.C. (1979) The Spandrels of San Marco and the Panglossian Paradigm: A Critique of the Adaptationist Programme. Proceedings of the Royal Society of London. Series B, Biological Sciences, Vol. 205, No. 1161, The Evolution of Adaptation by Natural Selection (Sep. 21, 1979), pp. 581-598. [AAAS reprint] [printable version]

Secret Alien Messages in Your Genome

 
Today is the first day of my course on molecular evolution and I want the students to experience the give-and-take of scientific—and not so scientific—debate in the blogosphere.

Their first assignment is to read the following quotation from an article by Paul Davies and answer the question that follows.

Paul Davies is a professor at Arizona State University. He was trained as a physicist and he lists his interests as cosmology, quantum field theory, and astrobiology. The quotation is from an article he wrote last April in the Wall Street Journal [Is Anybody Out There?: After 50 years, astronomers haven't found any signs of intelligent life beyond Earth. They could be looking in the wrong places.]

Another physical object with enormous longevity is DNA. Our bodies contain some genes that have remained little changed in 100 million years. An alien expedition to Earth might have used biotechnology to assist with mineral processing, agriculture or environmental projects. If they modified the genomes of some terrestrial organisms for this purpose, or created their own micro-organisms from scratch, the legacy of this tampering might endure to this day, hidden in the biological record.

Which leads to an even more radical proposal. Life on Earth stores genetic information in DNA. A lot of DNA seems to be junk, however. If aliens, or their robotic surrogates, long ago wanted to leave us a message, they need not have used radio waves. They could have uploaded the data into the junk DNA of terrestrial organisms. It would be the modern equivalent of a message in a bottle, with the message being encoded digitally in nucleic acid and the bottle being a living, replicating cell. (It is possible—scientists today have successfully implanted messages of as many as 100 words into the genome of bacteria.) A systematic search for gerrymandered genomes would be relatively cheap and simple. Incredibly, a handful of (unsuccessful) computer searches have already been made for the tell-tale signs of an alien greeting.

Here's the question. Assume that the aliens inserted a 1000 bp message in the same place in the genomes of every member of our ancestral population from five million years ago. At that point every organism in the species had exactly the same message in a region of junk DNA.

If you were to sequence that very same region of your own genome what would the message look like today? Would it be different from the original message of five million years ago? Is there a way of reconstructing the original message and interpreting it?

Comments will be held until tomorrow evening in order to give everyone a fair shot at coming up with an answer.

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Photo Credit: Lieutenant Ellen Ripley communicates with aliens.

How to Do Good Science

Richard Feynman (1918–1988) was a very smart American physicist who's words are often quoted ... for good reason.

Here's one quotation where he describes how good scientists should behave. It's a point I make in my class on scientific controversies and it's worth emphasizing because so many modern scientists ignore it.

Feynman is specifically referrring to "cargo cult science" but his advice applies to a lot of of modern biology as well.

There is one feature I notice that is generally missing in "cargo cult science." It's a kind of scientific integrity, a principle of scientific thought that corresponds to a kind of utter honesty — a kind of leaning over backwards. For example, if you're doing an experiment, you should report everything that you think might make it invalid — not only what you think is right about it; other causes that could possibly explain your results; and things you thought of that you've eliminated by some other experiment, and how they worked — to make sure the other fellow can tell they have been eliminated.

Details that could throw doubt on your interpretation must be given, if you know them. You must do the best you can — if you know anything at all wrong, or possibly wrong — to explain it. If you make a theory, for example, and advertise it, or put it out, then you must also put down all the facts that disagree with it, as well as those that agree with it. There is also a more subtle problem. When you have put a lot of ideas together to make an elaborate theory, you want to make sure, when explaining what it fits, that those things it fits are not just the things that gave you the idea for the theory; but that the finished theory makes something else come out right, in addition.

In summary, the idea is to try to give all of the information to help others to judge the value of your contribution; not just the information that leads to judgment in one particular direction or another.

Richard Feynman, "Cargo Cult Science" in Surely You're Joking, Mr. Feynman!

Think about Feynman's words next time you read a paper on the importance of alternative splicing, the disappearance of junk DNA, or anything about evolutionary psychology.

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Splicing Error Rate May Be Close to 1%

Alex Ling alerted me to an important paper in last month's issue of PLoS Genetics. Pickrell et al. (2010) looked at low abundance RNAs in order to determine how many transcripts showed evidence of possible splicing errors. They found a lot of "alternative" spliced transcripts where the new splice junction was not conserved in other species and was used rarely. They attribute this to splicing errors. Their calculation suggests that the splicing apparatus makes a mistake 0.7% of the time.

This has profound implication for the interpretation of alternative splicing data. If Pickerell et al. are correct—and they aren't the only ones to raise this issue—then claims about alternative splicing being a common phenomenon are wrong. At the very least, those claims are controversial and every time you see such a claim in the scientific literature it should be accompanied by a statement about possible artifacts due to splicing errors. If you don't see that mentioned in the paper then you know you aren't dealing with a real scientist.

Here's the abstract and the author summary ..

Abstract

While the majority of multiexonic human genes show some evidence of alternative splicing, it is unclear what fraction of observed splice forms is functionally relevant. In this study, we examine the extent of alternative splicing in human cells using deep RNA sequencing and de novo identification of splice junctions. We demonstrate the existence of a large class of low abundance isoforms, encompassing approximately 150,000 previously unannotated splice junctions in our data. Newly-identified splice sites show little evidence of evolutionary conservation, suggesting that the majority are due to erroneous splice site choice. We show that sequence motifs involved in the recognition of exons are enriched in the vicinity of unconserved splice sites. We estimate that the average intron has a splicing error rate of approximately 0.7% and show that introns in highly expressed genes are spliced more accurately, likely due to their shorter length. These results implicate noisy splicing as an important property of genome evolution.

Author Summary

Most human genes are split into pieces, such that the protein-coding parts (exons) are separated in the genome by large tracts of non-coding DNA (introns) that must be transcribed and spliced out to create a functional transcript. Variation in splicing reactions can create multiple transcripts from the same gene, yet the function for many of these alternative transcripts is unknown. In this study, we show that many of these transcripts are due to splicing errors which are not preserved over evolutionary time. We estimate that the error rate in the splicing of an intron is about 0.7% and demonstrate that there are two major types of splicing error: errors in the recognition of exons and errors in the precise choice of splice site. These results raise the possibility that variation in levels of alternative splicing across species may in part be to variation in splicing error rate.

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Pickrell, J.K., Pai, A.A., and Gilad, Y., Pritchard, J.P. (2010) Noisy Splicing Drives mRNA Isoform Diversity in Human Cells. PLoS Genet 6(12): e1001236. doi:10.1371/journal.pgen.1001236

Extraordinary Claims about Human Genes

Sandra Porter of Discovering Biology in a Digital World has recently attended a talk by Chris Mason of Cornell University. According to Sandra, Chris Mason made the following claims based on his analysis of RNAs from various tissues (human? mammal?). [Next Generation Sequencing adds thousands of new genes]

1. A large fraction of the existing genome annotation is wrong.
2. We have far more than 30,000 genes, perhaps as many as 88,000.
3. About ten thousand genes use over 6 different sites for polyadenylation.
4. 98% of all genes are alternatively spliced.
5. Several thousand genes are transcribed from the "anti-sense"strand.
6. Lots of genes don't code for proteins. In fact, most genes don't code for proteins.

I bet that every one of those claims is wrong.

There's a saying about extraordinary claims—they require extraordinary evidence. In this case, I'm pretty sure the "evidence" is the detection of low abundance transcripts using highly sensitive sequencing technology. Anyone who's ever learned about DNA binding proteins knows about non-specific binding and they know that spurious transcription is inevitable. In order to overthrow our view of the number of genes and how they behave, you will have to convince me that you've ruled out accidental spurious transcription (junk RNA).

I think it's somewhat disingenuous to be giving a talk where you claim we have 88,000 genes and 98% of them are alternatively spliced. (The term "alternative splicing" implies biological significance and not just splicing errors.)

In order to evaluate transcriptome data we need to know the abundance of the transcript. It's not sufficient to simply report that such-and-such region of the genome was transcribed. Researchers have got to report the average number of transcripts per cell in the tissue they are analyzing. I'm betting that if we saw that data we would instantly recognize that the so-called new "genes" are producing less than one transcript per cell. If that's the case it can't be biologically significant in a large mammalian cell.

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How Similar Are Humans and Chimpanzees?

 
When it comes to comparing DNA sequences of individual genes, the human and chimp versions are almost identical in sequence. They differ by only 1-2%. That result gave rise to the oft-quoted similarity of 98-99%.

But that's not the whole story. Outside of the genes there's a large amount of DNA that's less similar. We know this because we now have the sequences of both the human and chimp genomes. Furthermore, there are sequences present in the human genome that are absent in the chimp genome and vice versa. If you look at the whole genomes, the overall similarity is about 95% or so depending on how you do the calculation.

Creationists make a big deal about this. They claim that the newest data proves that evolutionists are wrong and chimps aren't necessarily our cousins. The latest debate is between Fazale Rana on the Reasons to Believe (RTB) website and Dennis Venema on the BioLogos website. The important scientific point is about the actual similarity and how is it calculated?

Fortunately for us, Todd Wood of the Center for Origins Research at Bryan College in Dayton, Tennessee, USA is on the case. Todd belongs to a young-Earth creation study group [BSG] but don't let that fool you. He's doing a pretty good job of sorting out the facts in the case.

RTB and the chimp genome Part 1
RTB and the chimp genome Part 2
RTB and the chimp genome Part 3
RTB and the chimp genome Part 4
RTB and the chimp genome Part 5

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Photo Credit: chimpanzee.net

A Defense of the "Theistic Evolution" Version of Creationism

 
Conor Cunningham¹ has just published a defense of Christianity against the attack of Darwinism. I've ordered his book, Darwin's Pious Idea: Why the Ultra-Darwinists and Creationists Both Get it Wrong, and I look forward to commenting on it in future posts.

Meanwhile, here's an excerpt from his BBC series Did Darwin Kill God? You can see right away that there's going to be problem with someone who equates Darwin with modern evolutionary theory. It means that Cunningham lacks scientific credibility making his arguments mostly moot.

There might be a problem with his theology as well but that's not something I'm very interested in. Perhaps some theist can answer a question? If Genesis has always been taken metaphorically and not literally by the Christian church, then what about the rest of the Bible? Specifically, are Christian supposed to take the stories of Jesus as metaphor and not fact? Is the death and resurrection of Jesus something that never actually happened? Is it just a metaphor? What the official Christian view of this?

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Conor Cunningham is a lecturer in theology and religious studies at the University of Nottingham in the United Kingdom.

Iconic Delusions

 
I don't have much time for blogging these days 'cause I'm in the middle of writing a textbook—trying to be as accurate as possible.

Watch Paul Nelson making comments about the authors of biology textbooks. He sounds very sincere. I think he actually believes that biology textbook authors are deliberately lying. Poor deluded Paul Nelson. That's why we call them IDiots.

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A Test for True Christians

 
Denyse O'Leary doesn't think Theodosius Dobzhansky was a true Christian. She's angry at all those so-called "Christians" who accept evolution because, in her mind, science and Christianity are incompatible [If you are a Darwinist, can you be a Christian if people just say so ... ?].

What do you do about all those fake Christians who believe in theistic evolution? You develop a litmus test, of course.

... if you ask me whether someone is a Christian, I say, "Let him recite the Apostle's Creed and affirm that he believes it and renounces contrary doctrines."

Sounds like a plan. I'll quote the English Language Liturgical Consultation (ELLC) version of the Apostle's Creed and we can discuss whether believing it is compatible with science as a way of knowing. Doesn't look like it to me. Denyse is right!

I believe in God, the Father almighty,
   creator of heaven and earth.
I believe in Jesus Christ, God's only Son, our Lord,
   who was conceived by the Holy Spirit,
   born of the Virgin Mary,
   suffered under Pontius Pilate,
   was crucified, died, and was buried;
   he descended into hell.
   On the third day he rose again;
   he ascended into heaven,
   he is seated at the right hand of the Father,
   and he will come to judge the living and the dead.
I believe in the Holy Spirit,
   the holy catholic Church,
   the communion of saints,
   the forgiveness of sins,
   the resurrection of the body,
   and the life everlasting. Amen.

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Sign a Petition on CIHR Funding

 
Are you a Canadian researcher who cares about the dismal CIHR funding situation?

Sign the petition at: The CIHR Individual Grants Program. It may not do much good but at least you'll have 700+ friends (latest count).

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The Cause of Speciation

 
Jerry Coyne is an expert on speciation. That's why it's always informative to read his latest thoughts on the problem. In spite of what many people might believe, the main cause of reproductive isolation—the actual speciation event according to the biological species concept—is due to accident, not adaptation. It's just one more example of the importance of random genetic drift in evolution.

Here's how Coyne puts it in his latest posting [“Reinforcement” and the origin of species].

Genetic barriers aren’t thought to arise for the purpose of keeping species distinct. Rather, they are usually thought to be evolutionary accidents: geographically isolated populations diverge genetically under natural selection or other evolutionary forces like genetic drift, and that divergence leads to the evolution of genetic barriers (mate discrimination, the sterility of hybrids, ecological differences, etc.) as byproducts of evolutionary change. For example, populations could adapt to different environments (one dry, one wet, for example), leading to them becoming genetically different. When these populations meet each other again, this genetic divergence could result in hybrids that don’t develop properly because the parental genomes are sufficiently diverged that they can’t cooperate in building a single individual.

I wish more people would assimilate this message. It seems to be the overwhelming consensus among the experts in speciation but the average scientist still has an adaptationist view of speciation (and of evolution in general).

Speaking of adaptationists, Coyne also likes the idea that some examples of reproductive isolation can be reinforced by natural selection. You can read about those cases on his blog.

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Let Oprah know that Kim Tinkham died of cancer

 
Kim Tinkham died of cancer today. Orac wants you to Let Oprah know that Kim Tinkham died of cancer. I've already sent my message to Oprah. Why don't you send one?

Watch the video. Oprah sends very mixed messages. On the one hand she advises following the advice of doctors but at the same time she supports The Secret.

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DNA, Phosphorus, and Arsenic

Most of you know that DNA strands have a sugar-phosphate background. The bases in each strand are covalently linked to each other by phosphodiester linkages between the 5′ and 3′ carbon atoms of the deoxyribose sugar.

Recently there has been a claim by NASA-funded scientists that a certain bacterium can replace those phosphates with arsenic. Close examination of the Science paper has revealed that, at most, a few percent of the phosphorus atoms are replaced and even that amount is challenged. It has become abundantly clear from reading the paper that the bacteria absolutely required phosphorus and sufficient quantities were present in the media as contaminants.

I've already linked to Rosie Redfield's critiques of the paper and the press conference. Now I want to add Carl Zimmer's take on the whole affair—the title tells all: "This Paper Should Not Have Been Published".

Carl raises an issue that has cropped up in many of the comments sections of various blogs. Is criticizing a scientific paper appropriate outside of the peer-reviewed scientific literature? Is it ethical to cast doubt on the integrity of scientists when questioning the quality of their science?

Felisa Wolfe-Simon¹ is the lead author of the study and she was the main spokesperson in the video below. Carl Zimmer asked her if she wanted to respond to the criticism of her paper and here's what she said, according to the Slate article,

"Any discourse will have to be peer-reviewed in the same manner as our paper was, and go through a vetting process so that all discussion is properly moderated," wrote Felisa Wolfe-Simon of the NASA Astrobiology Institute. "The items you are presenting do not represent the proper way to engage in a scientific discourse and we will not respond in this manner."

Carl asked some other scientists about this and the best quote comes from Jonathan Eisen,

But Jonathan Eisen of UC-Davis doesn't let the scientists off so easily. "If they say they will not address the responses except in journals, that is absurd," he said. "They carried out science by press release and press conference. Whether they were right or not in their claims, they are now hypocritical if they say that the only response should be in the scientific literature."

My own impression of this fiasco is that the scientific authors of the paper can be accused of bad science and the lead author, Felisa Wolfe-Simon, is guilty of grossly misrepresenting her work at the press conference. There really can't be any excuse for that behavior if you want to call yourself a scientist. Those who think this is impolite and unethical are dead wrong. It's an absolute requirement of good science that we point out to the general public when scientists are behaving badly, otherwise we lose all credibility.

As you watch this video keep in mind that the bacteria absolutely require phosphate in the media in order to grow and that only a few phosphorus atoms, at most, are replaced by arsenic in DNA. If you think that's what Felisa Wolfe-Simon is telling you then you need to work hard on your listening comprehension skills.

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1. The name of the bacterial strain is GFAJ-1. Rumor has it that this stands for "Get Felissa a Job." I wonder how that's working out? Do you think the job offers are pouring in?