Alternative Splicing and Why IDiots Don't Understand How Science Works

One of the characteristics of creationists is their inability to understand how science works. For example, in biology, our knowledge of how living things work advances in fits and starts with many hypotheses being tested and rejected before we arrive at a consensus.

At any given point in time there are a number of "works in progress" where scientists have not settled on a definitive model. Many papers will be published and a good number of them will turn out to be wrong. Creationists exploit genuine scientific controversies in two ways: (1) they use them to discredit science, and (2) they selectively quote from those on one side of an issue without mentioning that many other scientists disagree. (Most creationists use both tactics, sometimes in the same paragraph.)

We saw how Jonathan Wells did this in The Myth of Junk DNA. He picked papers that question junk DNA and used them to try and show that the issue has not been settled in spite of what some leading scientists say. This is a valid point, but he goes on to conclude that junk DNA is a myth when the proper conclusion is that scientists haven't reached a consensus but the majority favor junk DNA.

He also selected specific papers that showed evidence of function for some part of the genome without mentioning that this evidence is often disputed. In many cases it isn't clear whether this "evidence" is correct. He ignores controversy when it suits him and exploits it when it's to his benefit.

Some papers have claimed that most of the human genome is transcribed. Wells takes this as evidence that the transcribed DNA is not junk. In this particular case, the objections to this interpretation couldn't be ignored so he spends a page or so dismissing the idea that the data might be wrong and that the conclusion might be wrong. He forgets to mention that the consensus among molecular biologists is that most of the transcript are junk RNA due to accidental transcription. The DNA being transcribed is still junk.

Jonathan M makes a similar mistake in his latest posting [Why the "Onion Test" Fails as an Argument for "Junk DNA"]. The issue is alternative splicing. There are many scientists who think that alternative splicing is widespread in the human genome. Some claim that the vast majority of human genes (>90%) make two or more biologically functional alternative transcripts. This is usually offered as one "explanation" for why humans don't have as many genes as our egos demand [The Deflated Ego Problem]. Fact is, most of us never thought this was a problem in the first place so no "solution" is required.

Here's how Jonathan M describes alternative splicing ....

Alternative Splicing and Genome Size

A second point I made was that the phenomena of alternative splicing and alternative polyadenylation may have some explanatory power when it comes to accounting for the C-value enigma. Alternative splicing allows a single form of a pre-mRNA transcript to be spliced into a number of different forms by skipping exons or by recognizing alternative splice sites. I stated that the level of alternative splicing exhibited in humans (more than 90%, with an average of 2 or 3 transcripts per gene) is much higher than that for C. elegans (about 22%, with less than 2 transcripts per gene), and argued that this may, in part, explain why humans have only marginally more genes than C. elegans, which is otherwise seemingly paradoxical given the complexity of humans as compared to the roundworm.

I don't really understand the connection between alternative splicing and the C-value paradox. How does it explain why closely related species of onion have very different genome sizes?

But that's not the point I want to make. When Jonathan M raised this issue before, I replied, "I don't agree with the facts. I don't think it's true that most human genes produce multiple functional copies of mRNA by alternative splicing."

That prompted the following response ...

On this point, Moran is not just in disagreement with me, he is also out-of-date with the literature by about ten years! As this 2008 article from Science Daily reports,

Nearly all human genes, about 94 percent, generate more than one form of their protein products, the team reports in the Nov. 2 online edition of Nature. Scientists' previous estimates ranged from a few percent 10 years ago to 50-plus percent more recently.

"A decade ago, alternative splicing of a gene was considered unusual, exotic ... but it turns out that's not true at all -- it's a nearly universal feature of human genes," said Christopher Burge, senior author of the paper and the Whitehead Career Development Associate Professor of Biology and Biological Engineering at MIT.

Wang et al. (2008), moreover, report in Nature,

Through alternative processing of pre-messenger RNAs, individual mammalian genes often produce multiple mRNA and protein isoforms that may have related, distinct or even opposing functions. Here we report an in-depth analysis of 15 diverse human tissue and cell line transcriptomes on the basis of deep sequencing of complementary DNA fragments, yielding a digital inventory of gene and mRNA isoform expression. Analyses in which sequence reads are mapped to exon-exon junctions indicated that 92-94% of human genes undergo alternative splicing, ~86% with a minor isoform frequency of 15% or more.

I've written about IDiots and alternative splicing before, especially their inability to understand what they're talking about [Jonathan Wells Weighs in on Alternative Splicing]. But the issue here is somewhat different. It's whether the idea that most human genes are alternatively spliced is a scientific fact or whether it's controversial. Like most IDiots, Jonathan M doesn't understand the subject well enough to know the difference.

Just because there are some papers making truly outlandish claims about alternative splicing doesn't mean they are correct—no matter where those papers are published. In order to understand science you have to dig deeper than that and decide whether the claims have been accepted.

The claim of abundant alternative splicing (i.e. the vast majority of human genes have two or more functional transcripts) has not been accepted. It's a scientific controversy. Hardly any molecular biologist believes that >90% of our genes produce functional alternative transcripts in spite what Jonathan M might believe.

In some cases it's a matter of definition. My colleague, Ben Blencowe, for example, has played a prominent role in promoting the idea that >90% of human genes are alternatively spliced (Pan et al, 2008) but he tells me that this does not mean that all alternative transcripts are functional. He concedes that many of the these transcripts could be due to splicing errors but they still qualify as alternative splicing events.

I don't agree with that definition. Many of us began teaching alternative splicing back in 1980 and putting in textbooks a few years later. "Alternative splicing" always meant "functional" alternatives. It means that the gene produced more that one biologically functional product. The definition changed in the past decade or so, but most people still interpret abundant alternative splicing to mean abundant functional products.

No reasonable molecular biologist could look at the database of spliced transcripts and conclude that most of them have a biological function. (See Two Examples of "Alternative Splicing" to see if you agree.) Most of those transcripts are clearly due to splicing errors just as most of the minor genome transcripts are due to transcription errors. There's just as much junk splicing as there is junk RNA.

Anyone familiar with the subject of alternative transcription knows that the conclusions are controversial. They know that many scientists are skeptical of the claims for massive amounts of functional alternative splicing. They know that those extraordinary claims don't make sense in the light of evolution and are probably wrong. (See A Challenge to Fans of Alternative Splicing.)

Here are some papers from well-known labs attempting to deal with the controversy.

Zhang et al. (2009)

Nonsense-mediated decay is a mechanism that degrades mRNAs with a premature termination codon. That some exons have premature termination codons at fixation is paradoxical: why make a transcript if it is only to be destroyed? One model supposes that splicing is inherently noisy and spurious transcripts are common. The evolution of a premature termination codon in a regularly made unwanted transcript can be a means to prevent costly translation. Alternatively, nonsense-mediated decay can be regulated under certain conditions so the presence of a premature termination codon can be a means to up-regulate transcripts needed when nonsense-mediated decay is suppressed....

We conclude that for recently evolved exons the noisy splicing model is the better explanation of their properties, while for ancient exons the nonsense-mediated decay regulated gene expression is a viable explanation.

Tress et al. (2007)

Alternative premessenger RNA splicing enables genes to generate more than one gene product. Splicing events that occur within protein coding regions have the potential to alter the biological function of the expressed protein and even to create new protein functions. Alternative splicing has been suggested as one explanation for the discrepancy between the number of human genes and functional complexity. Here, we carry out a detailed study of the alternatively spliced gene products annotated in the ENCODE pilot project. We find that alternative splicing in human genes is more frequent than has commonly been suggested, and we demonstrate that many of the potential alternative gene products will have markedly different structure and function from their constitutively spliced counterparts. For the vast majority of these alternative isoforms, little evidence exists to suggest they have a role as functional proteins, and it seems unlikely that the spectrum of conventional enzymatic or structural functions can be substantially extended through alternative splicing.

Melamud and Moult (2009)

The number of known alternative human isoforms has been increasing steadily with the amount of available transcription data. To date, over 100 000 isoforms have been detected in EST libraries, and at least 75% of human genes have at least one alternative isoform. In this paper, we propose that most alternative splicing events are the result of noise in the splicing process. We show that the number of isoforms and their abundance can be predicted by a simple stochastic noise model that takes into account two factors: the number of introns in a gene and the expression level of a gene. The results strongly support the hypothesis that most alternative splicing is a consequence of stochastic noise in the splicing machinery, and has no functional significance. The results are also consistent with error rates tuned to ensure that an adequate level of functional product is produced and to reduce the toxic effect of accumulation of misfolding proteins. Based on simulation of sampling of virtual cDNA libraries, we estimate that error rates range from 1 to 10% depending on the number of introns and the expression level of a gene.

This is a controversial topic. Some of us believe that alternative splicing in human genes is not particularly widespread and most of the data can be explained as errors in splicing. Others believe that the data is real and most human genes produce multiple transcripts with different biological functions.

It doesn't matter so much which side you pick. What matters is that you understand science well enough to know that the data and the conclusions are disputed. What this means is that you cannot just assume that >90% of human genes are alternatively spliced and use this "fact" to bolster your case for Intelligent Design Creationism.

I'm tempted to say that Jonathan M is "... out-of-date with the literature by about ten years!" but that would be unkind.

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Melamud, E. and Moult, J. (2009) Stochastic noise in splicing machinery. Nucleic Acids Res. 37:4873-4886. [doi: 10.1093/nar/gkp471]

Pan, Q., Shai, O., Lee, L.J., Frey, B.J., and Blencowe, B.J. (2008) Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat Genet. 2008 Dec;40(12):1413-5. Epub 2008 Nov 2. [doi:10.1038/ng.259]

Tress, M.L., Martelli, P.L., Frankish, A., Reeves, G.A., Wesselink, J.J,, Yeats, C., Olason, P.I., Albrecht, M., Hegyi, H., Giorgetti, A., Raimondo, D., Lagarde, J., Laskowski, R.A., López, G., Sadowski, M.I., Watsonk J.D., Fariselli, P., Rossi, I., Nagy, A., Kai, W., Størling, Z., Orsini, M., Assenov, Y., Blankenburg, H., Huthmacher, C., Ramírez, F., Schlicker, A., Denoeud, F., Jones, P., Kerrien, S., Orchard, S., Antonarakis, S.E., Reymond, A., Birney, E., Brunak, S., Casadio, R., Guigo, R., Harrow, J., Hermjakob, H., Jones, D.T., Lengauer, T., Orengo, C.A., Patthy, L., Thornton, J.M., Tramontano, A., and Valencia, A. (2007) The implications of alternative splicing in the ENCODE protein complement. Proc. Natl. Acad. Sci. USA 104:5495-5500. [doi: 10.1073/pnas.0700800104]

Zhang, Z., Xin, D., Wang, P., Zhou, L., Hu, L., Kong, X., and Hurst, L.D. (2009) Noisy splicing, more than expression regulation, explains why some exons are subject to nonsense-mediated mRNA decay. BMC Biol. 7:23-36. [doi:10.1186/1741-7007-7-23]

Jonathan M Flunks the Onion Test, Again

 

A few weeks ago I explained why Jonathan M is an IDiot [A Twofer]. The topic was junk DNA. Jonathan M had posted an article on Uncommon Descent where he claimed that The Onion Test is an argument in favor of junk DNA [Thoughts on the “C-Value Enigma”, the “Onion Test” and “Junk DNA”].

I explained, as politely as I could (not), that the onion test was not an argument in support of junk DNA. It's a "test" for those who think they can explain the presence of large amounts of supposedly functional DNA that looks a lot like junk. The "test" is to apply your reasoning to the genomes of various onion species to see if it makes sense.

Do you think that the excess DNA protects against mutations? Then why do some onions need a lot more protection than humans?

Do you think that the extra DNA can be explained by alternative splicing? Why do some onion species need more alternative splicing than others?

Do you think that most of the extra DNA is required for regulating gene expression? Then why do onions need more sophisticated regulation than humans?

This ain't rocket science. The description of the Onion Test is pretty easy to understand—unless, of course, you are an IDiot.

Jonathan M has taken another shot at attacking the Onion Test. This time his article appears on the official blog of The Discovery Institure: Why the "Onion Test" Fails as an Argument for "Junk DNA". The title sort of gives it away, doesn't it? We're still dealing with an IDiot.

Briefly stated, the often cited "onion test" observes that onion cells have many times more DNA than human cells do. And since the onion is considered to be relatively simple as compared to us, this discrepancy -- it is argued -- can only be accounted for if the preponderance of its DNA is, in fact, junk or non-functional. Let's see whether the concept really holds any water.

Let's go over this one more time. The Onion Test is a "test." (Look up the word "test" in the dictionary.) It's designed as a thought experiment to test a hypothesis about the possible function of large amounts of noncoding DNA. If you think you have an explanation for why most of the human genome has a function then you should explain how that accounts for the genomes of onions. Ryan Gregory knew that most so-called explanations look very silly when you try using them to account for genome size in onion species.

The Onion Test is not an argument in favor of junk DNA. It's a reality check on speculations about function.

Jonathan M still doesn't get it.

Are we surprised?

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Carnival of Evolution #41

 
This month's Carnival of Evolution (41st version) is hosted by Anne Buchanan, from the Anthropology Department at Pennsylvania State University (USA). She blogs with her friends at the mermaid's tale: The Carnival of Evolution #41.

Each month, a fascinating hodge-podge of evolution-themed posts from blogs both big and small is collected in a single place and heralded far and wide. Or as far and wide as interested bloggers can herald it. Evolution is a broad topic with broad areas of agreement, some controversy (within the science itself), and regular surprises. So, if you're interested in evolutionary issues, post, tweet, text, or even speak the 41st CoE!

The next Carnival of Evolution will be hosted by Psi Wavefunction at The Ocelloid. You can submit your articles for next month's carnival at Carnival of Evolution. Here's the website: Carnival of Evolution.

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Better Biochemistry: The Free Energy of ATP Hydrolysis

This is part of a series on important concepts in biochemistry. I'm concentrating on those concepts that may be widely misunderstood and/or not well described in most textbooks. Naturally, I think we do a pretty good job in our book!

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We usually think of ATP as a "high energy" molecule because the hydrolysis of ATP to ADP or AMP releases a lot of energy.¹ The standard Gibbs free energy change for the two reactions shown in the large figure aren't terribly relevant because, for simplicity, I've left out a key component of the reaction.

Mg²⁺ ions are an essential part of the reaction in vivo. They are bound to adjacent phosphate groups as shown below and this ATP:Mg²⁺ complex has different thermodynamic properties than free ATP.

In addition, the standard Gibbs free energy changes aren't very useful when you're dealing with charged molecules and the ATP hydrolysis reactions have charged molecules—even when some of the negative charges are neutralized by Mg²⁺ ions. That's why it's better to calculate new values of "standard" Gibbs free energy changes in the presence of Mg²⁺ ions and an ionic strength that's closer to physiological values.

Recall that the traditional standard Gibbs free energy changes are at 25°C (298 K) and pH 7.0. For reactions like ATP hydrolysis, we want a new "standard" that includes 3mM Mg²⁺ and ionic strength = 0.25 M.

Robert Alberty and his colleagues have calculated the transformed free energies of hydrolysis for many biochemical compounds (Alberty and Goldberg 1992) and those are the values we should use in biochemistry courses.

The table (below right) shows the standard Gibbs free energy changes for the ATP reactions in the presence of 3 mM²⁺ and ionic strength = 0.25 M. Note that the values are large and negative. That means a lot of energy is given off. This energy can be captured and used in enzyme catalyzed reactions.

If you've been paying attention to the previous postings in this series—as I'm sure you have—you'll remember that standard Gibbs free energy changes don't mean very much in biochemistry. What really counts is the actual free energy change and that depends on the in vivo concentrations of reactants and products.

You'll also remember that most biochemical reactions reach equilibrium (near-equilibrium reactions). At equilibrium concentrations ....

ΔG_reaction = 0 kJ mol^-1.

ATP would be completely useless as a "high-energy" compound if the hydrolysis reaction was a near-equilibrium reaction. That's why these reactions can never be allowed to reach equilibrium. Cells would die if this ever happened.

Most of the reactions that use up ATP are regulated. What this means is that the activity of the enzyme is inhibited if the concentration of ATP falls too much, relative to ADP (or AMP). If the concentration of ATP is always high relative to the products then there's still a large negative ΔG for the reaction and this energy can be used to drive other reactions.

So, we know that the actual Gibbs free energy isn't the same as the standard Gibbs free energy but what is it's actual value? The short answer is that in most cases we don't know. It has to be some large negative value but it's very difficult to measure the concentrations of ATP, ADP, AMP, and inorganic phosphate inside cells.

The situation isn't entirely hopeless since there are some good estimates. Unfortunately the best examples come from rat hepatocytes and erythrocytes¹. We don't know if this is typical of all cells (bacteria, plants etc.) or whether mammalian cells are special.

We can calculate the actual Gibbs free energy change for ATP hydrolysis (to ADP) given the known concentrations of reactants and products in rat hepatocytes. The answer is ΔG = -48 kJ mol^-1. Thus, the actual Gibbs free energy change is 1½ times the standard Gibbs free energy change. This has important consequences when we try to figure out how ATP is synthesized and where that energy comes from.

There's an easy way to tell the difference between a good introductory biochemistry textbook and the other kind. Check out the standard Gibbs free energy change for the ATP → AMP + PP_i reaction. If the value is close to -45 kJ mol^-1 then it's probably a good textbook. If the book also mentions that the actual Gibbs free energy of the ATP → ADP + P_i reaction is close to -50 kJ mol^-1 then it's almost certain to be a good textbook.

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1. I put "high energy" in quotation marks because it's really the Gibbs free energy of the reaction (system) that we're referring to and not an individual molecule.

2. Rat liver biochemistry used to be very popular.

Alberty, R.A. and Goldberg, R.N. (1992) Standard thermodynamic formation properties of adenosie 5′-triphosphate series. Biochem. 31:10610-10615.

Monday's Molecule #147

 

Give me the complete, unambiguous, name of this molecule to win a free lunch. Post your answer in the comments. I'll hold off releasing any comments for 24 hours. The first one with the correct answer wins. I will only post correct answers to avoid embarrassment.

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 comment.) Every undergraduate who posts a correct answer will have their names entered in a Christmas draw. The winner gets a free autographed copy of my book! (One entry per week. If you post a correct answer every week you will have ten chances to win.)

Some past winners are from distant lands so their chances of taking up my offer of a free lunch are slim. (That's why I can afford to do this!)

Name the molecule shown in the figure. Remember that your name has to be unambiguous. The best way to do this is to use the full IUPAC name but usually there are traditional names that will do.

Winners
Nov. 2009: Jason Oakley, Alex Ling
Oct. 17: Bill Chaney, Roger Fan
Oct. 24: Bill Chaney

UPDATE: The winner is Joseph C. Somody.

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Introducing the Scientific Theory of Redemptive Suffering

 

Before introducing you to this new scientific theory we need to remind ourselves of the difference between intelligent design and creationism. This is from the Evolution News & Views website [Is intelligent design the same as creationism?]

Is intelligent design the same as creationism?

No. The theory of intelligent design is simply an effort to empirically detect whether the "apparent design" in nature acknowledged by virtually all biologists is genuine design (the product of an intelligent cause) or is simply the product of an undirected process such as natural selection acting on random variations. Creationism typically starts with a religious text and tries to see how the findings of science can be reconciled to it. Intelligent design starts with the empirical evidence of nature and seeks to ascertain what inferences can be drawn from that evidence. Unlike creationism, the scientific theory of intelligent design does not claim that modern biology can identify whether the intelligent cause detected through science is supernatural.

Honest critics of intelligent design acknowledge the difference between intelligent design and creationism. University of Wisconsin historian of science Ronald Numbers is critical of intelligent design, yet according to the Associated Press, he "agrees the creationist label is inaccurate when it comes to the ID [intelligent design] movement." Why, then, do some Darwinists keep trying to conflate intelligent design with creationism? According to Dr. Numbers, it is because they think such claims are "the easiest way to discredit intelligent design." In other words, the charge that intelligent design is "creationism" is a rhetorical strategy on the part of Darwinists who wish to delegitimize design theory without actually addressing the merits of its case.

John Blumenthal wrote a piece at Huffington Post where he tried to apply this approach [Intelligent Design? Not If You're Over 50]. He noted that, "If you're over 50 and your body is starting to fall apart, it's pretty obvious that the design is anything but intelligent." I'm told that Blumenthal used to be an editor at Playboy magazine.

An anonymous correspondent at the Discovery Institute's blog, Evolution News & Views, decided to set Blumenthal straight by giving us the scientific, non-creationist, intelligent design, explanation [My Back Hurts Therefore It Wasn't Designed].

For some reason, the former Playboy magazine editor has never heard of redemptive suffering and assumes that any Designer worth his salt would have created a universe where everyone has a rollicking orgy in his own Playboy Mansion until one day, he has a painless death. How cruel of the Designer not to have taken Hugh Hefner's plan for a fulfilling life as a model.

Redemptive Suffering? I try to keep up with the scientific literature but that's a new one on me. It can't have anything to do with trying to deduce the motives of the Christian God of the Bible, can it?

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Beavers vs Polar Bears

 
Here's the complete press release from Canadian Senator Nicole Eaton issued just a few days ago [Statment about the Polar Bear]. Her proposal has been widely publicized. Most people think it's a serious suggestion from the Conservative Government. I'll treat it in the spirit that it was intended.

The Case for Socialized Medicine

 
From MNT: Medical New Today.

Religious, Spiritual Support Benefits Men And Women Facing Chronic Illness, MU Study Finds

Individuals who practice religion and spirituality report better physical and mental health than those who do not. To better understand this relationship and how spirituality/religion can be used for coping with significant health issues, University of Missouri researchers are examining what aspects of religion are most beneficial and for what populations. Now, MU health psychology researchers have found that religious and spiritual support improves health outcomes for both men and women who face chronic health conditions.

"Our findings reinforce the idea that religion/spirituality may help buffer the negative consequences of chronic health conditions," said Stephanie Reid-Arndt, associate professor of health psychology in the School of Health Professions. "We know that there are many ways of coping with stressful life situations, such as a chronic illness; involvement in religious/spiritual activities can be an effective coping strategy."

Religious and spiritual support includes care from congregations, spiritual interventions, such as religious counseling and forgiveness practices, and assistance from pastors and hospital chaplains. The recent publication from the MU Center for Religion and the Professions research group, authored by Reid-Arndt, found that religious support is associated with better mental health outcomes for women and with better physical and mental health for men.

In a society that believes in individualism, it's good to find a group that will help you and your family in your time of need. It doesn't matter whether that group is your local Lion's Club, your Jehovah's Witness Kingdom Hall, or your Harvard Alumni buddies.

If you live in such a society and you're too poor to afford decent health care, then the group could save your life.

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[Hat Tip: Uncommon Descent, although Denyse reaches a different conclusion.]

Wise Beyond Her Years

 
The Dallas News published an interview with 9-year-old Mason Crumpacker. You might remember her as the girl who asked Christopher Hitchens about his favorite books. Since most of us don't read the Dallas News¹, Jerry Coyne posted the entire interview on his blog website: Interview with a 9-year-old skeptic.

I'm stealing the entire interview from Jerry's website and reproducing it here just in case there are some Sandwalk readers who might not look at Why Evolution Is True and might not read the Dallas News².

Why can't we create a society where every child can give answers like this?

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Creationism and Climate Change Denial: What's the Connection?

 
You probably know already that creationists are more likely to fall for other kooky ideas like denying that humans cause global climate change. Do they just have a fondness for stupid ideas or is there some kind of connection between creationism and disbelief in anthropomorphic climate change?

GilDodgen explains the "logic" at: Junk Science as Ersatz Religion.

Why are ID theorists skeptical of “man-caused carbon dioxide emissions leading to the destruction of the planet” theory? The reason is that we follow the evidence, and have a nose that smells out junk science in the name of an ideological (indeed, a religious) agenda.

At a recent men’s church retreat I chatted with our pastor about how it seemed obvious to me that the global-warming thing exhibited all the attributes of a religion.

Mother earth is a goddess. We have sinned against her with technology. If we do not repent and return to primitive living she will call down her wrath and fry us all with vengeance.

Little did I know that Michael Barone, in his essay Collapse of the global-warming cult came to the same conclusion.

The same thing applies to the cult of Darwinism, which is promoted in the name of science. Darwinian theory (in particular, the presumed creative power of random mutations, and attempts to explain away the fact that the fossil evidence consistently contradicts gradualism) exhibits all the attributes of an ersatz religion.

It is the creation story of the religion of materialism.

Turns out I was right the first time. They're just kooks.

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The Core Genome

Hundreds of genomes have been sequenced. It should be relatively easy to search all these genomes to identify those genes that are found in every single species. This small class of genes should represent the core genome—the genes that were probably present in the first living cell.

Turns out it's not that easy. For one thing, you have to remove parasitic bacteria from your set of genomes because these species could easily be getting by without some essential genes that are supplied by their hosts. Next you have to make sure you have a huge variety of different species that cover all possible forms of life. In practice, this means that you need about 300 different genomes, mostly bacteria.

I'm reading The Logic of Chance: The Nature and Origin of Biological Evolution, by Eugene Koonin. This is just one of many books that are critical of the most popular views of evolution. Most of these books are written by kooks or religious nutters but some of them are valid scientific critiques of modern evolutionary theory. Koonin's book is one of those and I agree with most of what he has to say. One of his topics is genome evolution.

As Koonin describes it, the first genome comparisons looked at Haemophilus influenzae and Mycoplasma genitalium, two species of bacteria that aren't distantly related. There were about 240 orthologous genes found in both species.¹ The first surprise was that this core set was missing some very important members that should have been there.

Some essential metabolic reactions must have been catalyzed by enzymes in the very first cells but the Haemophilus enzyme isn't present in Mycoplasma and vice versa. It took a bit of digging but eventually the problem was solved with the discovery of different enzymes that carried out the same reaction. The genes for these enzymes are completely unrelated.

As more and and more genomes were sequenced, the size of the core genome set shrunk until today it comprises fewer than 100 genes. Most of these genes are genes for the three ribosomal RNAs, about 30 tRNAs, and a few other essential RNA molecules. There are only about 33 protein-encoding genes in the universal core set. They include genes for the three large RNA polymerase subunits and 30 proteins required for translation (mostly ribosomal proteins).

DNA polymerase isn't in the core set because some species of bacteria have unusual DNA polymerases that replicate DNA just fine but are unrelated to the enzymes found in most cells. There are multiple, unrelated, versions of the aminoacyl tRNA synthetases—the enzyme that attaches an amino acid to its cognate tRNA. Some species have one version and other species have the second version. Some species have both. In any case, no single synthetase gene is found in every species so it's not part of the core set.

Koonin refers to this observation as non-orthologous gene displacement (NOGD). He envisages a scenario where a cell with gene X takes up a copy of a non-orthologous gene (gene Y) that catalzyes the same reaction. Over time the newly acquired gene displaces the original version. In this way a non-orthologous version (e.g. gene Y) could have arisen after the formation of the first cell and spread to a variety of different species by horizontal gene transfer. The scenario doesn't rule out the possibility that the two non-orthologous versions could have arisen independently in two separate origins of life but this seems less likely.

Let's look at a couple of examples. Biochemistry textbook writers have known for decades that there are different versions of some common metabolic genes ² The aldolase enzyme in gluconeogenesis & glucolysis is a classic. Some species have the class I enzyme/gene while others have the class II enzyme/gene. Some species have both.

This is an example of convergent evolution. The enzymes have different mechanisms and, as you can see from the figure, completely different structures. It doesn't seem to matter if a species has a class I enzyme or a class II enzyme since both enzymes are very good at catalyzing the fusion of two three-carbon molecules into a six-carbon fructose molecule or cleaving the six-carbon molecule in the reverse reaction.

The pyruvate dehydrogenase complex (PDC) is a huge enzyme that catalyzes an important metabolic reaction making acetyl-CoA—the substrate for the citric acid cycle. It seemed likely that every single species would have the genes for all of the PDC subunits but many species of bacteria were missing the entire complex. They have a different enzyme, pyruvate:ferredoxin oxidoreducatase that catalyzes a similar reaction. The enzymes have completely different mechanisms and are unrelated.

In this case, we have reason to believe that the enzyme requiring ferredoxin is more primitive and the more common pyruvate dehydrogenase complex evolved later. The PDC genes displaced the gene for pyruvate:ferredoxin oxidoreductase in many, but not all, species. That's why the genes for neither enzyme are part of the core set.

We don't know whether the existing core set of 100 genes truly represents genes that were present in the first living cell or whether they completely displaced the original versions. The fact that many of these genes are part of large operons might have made it easier for them to be transferred by horizontal gene transfer. (The selfish operon model.)

The bottom line is that attempts to reconstruct the genome of the first cell have failed because of NOGD and we now have to incorporate that concept into our way of thinking about early evolution. The good news is that the evolution of completely new genes seems to be much easier than we first imagined. We even have examples of three or four completely different enzymes carrying out the same reaction.³

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1. Koonin refers to conserved genes as Clusters of Orthologous Genes or COGs. It actually counts conserved domains rather than entire genes but the differences aren't great so I'll just refer to them as genes.

2. That is, those textbook writers that emphasize comparative biochemistry or an evolutionary approach to biochemistry. Some textbooks just cover human (mammalian) biochemistry so they won't even mention whether bacteria do biochemistry.

3. I'm not sure how the Intelligent Design Creationists explain these observations. Maybe there were several different designers who each came up with their ideal solution to the problem? Maybe there was only one designer who just got a kick out of making different versions of the same enzyme activity but got bored at only two or three?

Atheist Calls Religious People 'Idiots' On British Debate Show

 
Good for her. Kate Smurthwaite tells it like it is! It's fun to watch the theists try to defend themselves. Note that none of them tries to offer a rational explanation for their belief in heaven.

Kate's statement is undoubtedly something that the accommodationists would complain about. They probably thing it's counter-productive to point out that believing in heaven makes about as much sense as believing in the tooth fairy.

They probably think it's perfectly respectable to say that all aborted babies are in heaven. In most other contexts, people making statements like that would be candidates for the loony bin and nobody would be criticized for saying so. But if you say stupid things in the name of religion you need to be protected from criticism. According to theists, it has to be "rude" to criticize faith because otherwise it might be subjected to the same scrutiny that we reserve for belief in homeopathy, UFO abductions, and 9/11 conspiracy theories.

Society will undoubtedly fall apart if we criticize religious faith, right? I think we're about to find out.

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[Hat Tip: Friendly Atheist]

Read Kate Smurthwaite's blog: CRUELLA_BLOG

The "Intelligent Design" Version of Creationism

The IDiots are at it again. Over the past few months there's been an noticeable increase in the number of whining complaints about the way Intelligent Design Creationism is being treated in the popular press and on science blogs.

Here's the latest from David Klinghoffer on the Discovery Institute website: Here There Be Dragons: The Journalists' War on Science. Kinghoffer thinks that his movement is being treated unfairly by journalists. Let's see why.

If there's one thing we've learned from repeated uniform experience it is that on one scientific issue, the most contentious there is -- evolution -- it's treated as taboo for writers to inform themselves properly, to know the facts and evidence behind the scientific challenge to Darwinian theory.

Hmmm ... here's an Intelligent Design Creationist complaining that his critics haven't taken the time to "inform themselves properly" about a 100-year old version of evolutionary theory that's been modified and extended so that modern evolutionary theory no longer qualifies as "Darwinian theory." I don't know a single IDiot who has the gumption to refer to modern evolutionary theory by its proper description. I'm not even sure there's a single IDiot who understands modern evolutionary theory. That includes David Klinghoffer [see, The IDiots Respond].

Can you say "hypocrisy"?

Detecting God's Signature

Stephen Meyer has two main objectives. He wants to prove that Intelligent Design Creationism is the best explanation for the origin of information in the cell and he wants to prove that Intelligent Design Creationism is genuine science.

Let's look at the form of argument he uses in Signature in the Cell: DNA and the Evidence for Intelligent Design. This is from Chapter 17 where he's trying to refute the accusation that Intelligent Design Creationism is nothing more than an argument from ignorance.

... the argument made in this book ... takes the following form:

Premise One: Despite a thorough search, no material causes have been discovered that demonstrate the power to produce large amounts of specified information.
Premise Two: Intelligent causes have demonstrated the power to produce large amounts of specified information.
Conclusion: Intelligent design constitutes the best, most causally adequate, explanation for information in the cell.

Or, to put it more formally, the case for intelligent design made here has the form:

Premise One: Causes A through X do not produce evidence E.
Premise Two: Cause Y can produce E.
Conclusion: Y explains E better that A through X.

In addition to a premise about how material causes lack demonstrated causal adequacy, the argument for intelligent design as the best explanation also affirms the demonstrated causal adequacy of an alternative cause, namely, intelligence. This argument does not omit a premise providing positive evidence or reasons for preferring an alternative cause or proposition. Instead, it specifically includes such a premise. Therefore, it does not commit the informal fallacy or arguing from ignorance. It's really as simple as that.

Scientist are often accused of picking on the most idiotic of the IDiots and avoiding the really big guns who have all the best arguments for Intelligent Design Creationism.¹ See A Reason to Doubt the Real, Rather than Pretended, Confidence of Darwin Advocates, where David Klinghoffer asks,

How about answering the arguments of a real scientist who advocates intelligent design on scientific rather than Bible-thumping grounds -- a Douglas Axe or Ann Gauger, for example? How about a thoughtful critique of The Myth of Junk DNA or Signature in the Cell? A response to serious science bloggers like ENV's Casey Luskin or Jonathan M.?

So, here's my response to the very best that the IDiots can offer.

Premise One

Despite a thorough search, no material causes have been discovered that demonstrate the power to produce large amounts of specified information.

On the surface this looks like a purely scientific statement. I'm sure that most creationists accept it at face value since the leaders of the movement have been saying for years that evolution can't account for specified complexity or irreducible complexity.

Stephen Meyer is a philosopher but he's confident that his knowledge of biology is sufficient to establish the truth of this claim. He says on page 341 ...

Undirected materialistic causes have not demonstrated the capacity to generate significant amounts of specified information.

This is an important point since the logic of his argument depends on establishing that specified complexity can never arise from natural (materialistic) causes. You might think that a large part of this book would be devoted to backing up his premise. You would be wrong. Turns out, the real premise isn't exactly how it appears above.

Dennis Venema has written a critical review of Signature in the Cell and one of his criticisms is that there are many excellent examples of new information evolving by entirely materialistic mechansims that not violate the laws of physics and chemistry [Seeking a Signature]. We're all familiar with the examples of gene duplication and divergence but he might just as well have used dozens of other examples where specified complexity evolved. The wings of birds are for flying but they evolved from legs and fins. The irreducibly complex citric acid cycle evolved from simpler pathways.

These examples establish beyond a shadow of a doubt that there are perfectly reasonable, materialistic explanations for the evolution of specified complexity. That seems to negate Premise One.

Hang on. Meyer responds to the Venema criticism by pointing out that he was not referring to the origin just any specified information. He was only referring to the kind of specified information that appeared when life first formed. It's an origin of life problem.

The balance of [Venema's] review is spent refuting an argument that Signature in the Cell does not make and, thus, the evidence he cites is irrelevant to the main argument of the book; in short, Venema "refutes" a straw man. ... I happen to think -- but do not argue in Signature in the Cell -- that there are significant grounds for doubting that mutation and selection can add enough new information to account for various macroevolutionary innovations. Nevertheless, the book that Venema was reviewing, Signature in the Cell, does not address the issue of biological evolution, nor does it challenge whether mutation and selection can add new information to DNA. That is simply not what the book is about. Instead, it argues that no undirected chemical process has demonstrated the capacity to produce the information necessary to generate life in the first place. The book addresses the subject of chemical evolution and the origin of life, not biological evolution and its subsequent diversification. To imply otherwise, as Venema does, is simply to critique a straw man. [Stephen Meyer Resonds]

Meyer is correct. The book is about the origin of life and the problem of getting information into DNA 3.5 billion years ago, before there were cells, and before evolution. Meyer isn't always clear about this distinction but the argument that he frames above is about the origin of life.

Here's how he should have expressed Premise One ...

After decades of research, biologists have good explanations of how specified information can arise by evolution but they do not have a good explanation of how life began 3.5 billion years ago.

Premise Two

Intelligent causes have demonstrated the power to produce large amounts of specified information.

He's referring, of course, to the fact that bees make beehives and beavers make dams. There are hundreds of examples where animals produce complex structures full of specified information. That's what he means by "intelligent causes." All of this creation obeys the laws of physics and chemistry, therefore the explanation is entirely materialistic.

Don't forget that the argument is not about the creation of specified information throughout the history of life. It's about the ultimate origin of the information. Animals can create complex structures just as living cells can create new genes. What Meyer really wants to know is where do animals get this ability? Where did the information to create more information come from?

Animals evolved from more primitive ancestors. It's quite reasonable to postulate that all animals evolved from a common ancestor that had very rudimentary intelligence and that intelligence evolved from primitive neurons. Thus, the ability of intelligent animals to create complex structures—like pocket watches—ultimately traces back to the origin of life.

We can re-word Premise Two ...

Intelligent animals can produce large amounts of specified information by purely materialistic means. The ability to do this depends on the evolution of animals from the first living cells that arose 3.5 billion years ago.

Conclusion

Intelligent design constitutes the best, most causally adequate, explanation for the information in the cell.

This conclusion does not follow from either of the corrected premises.

Here's a better conclusion.

All of the information we see in biology, including the ability of beavers to make dams, can be traced back to the information present in the first cells. We don't currently have a good explanation for how DNA and cells arose.

It's difficult to see how you can squeeze a supernatural intelligent designer into this conclusion. Whenever we have good explanations for the origin of specified complexity, those explanations involve materialistic actions and not actions that require violation of the known laws of physics and chemistry. Beavers do not wave a wand to poof their dams into existance and bees don't get their beehives by praying for them

Therefore, it seems quite reasonable to assume that all examples of biological information arise by natural means, including the very earliest examples of DNA in the first cell.

(I don't address information theory, which takes up a significant part of the book for some unknown reason. See Jeffrey Shallit's take-down on Stephen Meyer in: More on Signature in the Cell.)

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1. Atheists have the same problem. We're always going after the most stupid theists and avoiding the really sophisticated arguments for the existence of God. You'll find a list of those arguments at: A Challenge to Theists and their Accommodationist Supporters.

Is Creationism Anti-Science?

 

It's very hard to define science—it's the demarcation problem and, in spite of what you've been told, philosophers don't agree on how to define science.

A lot of the activities of Intelligent Design Creationists qualify as science, as far as I'm concerned. That's why I spend so much time arguing against their attacks on evolution. Many of the IDiots accept common descent. Their attacks on other aspects of evolution aren't much different than similar attacks from legitimate, non-theistic scientists (e.g. objecting to junk DNA, questioning the Cambrian explosion, challenging strict Darwinism). It counts as "science" but it's very bad science and it's wrong.

All IDiots are anti-evolution but some go farther than others. If you are a Young Earth Creationist who believes that the universe was created less than 10,000 years ago, then you are not just anti-evolution, you are anti-physics, anti-chemistry, anti-geology, anti-astronomy, and anti-biology. I think it's fair to say that Young Earth Creationists are anti-science. This includes most (all?) of the Republican Presidential candidates in the United States and more than half the citizens of that country.

The only way YECs can possibly justify their strange beliefs is to assume that all the experts in all those fields are completely wrong about the fundamental concepts in their discipline. How could they possibly trust anything else those scientists have to say about their areas of expertise?

Let me introduce you to a "new voice" in the Intelligent Design Creationist world. Here's what Evolution News & Views says about him [A New Voice in the Debate Over Evolution and Intelligent Design].

There is literally a new voice in the debate over evolution and intelligent design. If you're a regular listener to the Center for Science & Culture's very popular and thrice weekly podcast, ID The Future, you have probably come to recognize familiar personalities, like ENV's Casey Luskin. (If you're not yet a listener, then you should be.) Now you will be hearing more often from radio broadcaster David Boze of Seattle's KTTH.

I assume David Boze is a heavy-weight and it's okay to criticize him.

Listen to the Discovery Institute podcast where Boze defends Young Earth Creationism against the charge that it's anti-science ["Anti-Science": Unpacking a Vague & Distorted Label]. (You can click on the embedded copy below.) Note the sleight of hand where he lumps together the Young Earth Creationists with all other IDiots. His point is that just because you're opposed to "atheistic Darwinian evolution" does not mean you're anti-science.

Perhaps not. But if you believe in the literal truth of the Bible then you are definitely anti-science. You are a genuine idiot. Does David Boze do a good job of defending Republican Presidential candidates against the charge of being anti-science? Will a YEC President harm the reputation of the United States? You be the judge.

Personally, I don't think the new kid on the block is much of a threat. Is this the best they can do?

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