3,000 new genes discovered in the human genome - dark matter revealed

Let's look a a recent paper published by a large group of medical researchers at the University of California, Los Angeles (USA). The paper was published online a few days ago (Oct. 26, 2015) in Nature Immunology.

The authors clam to have discoverd 3,000 previously unknown genes in the human genome.

The complete reference is ...

Jim Lake and the Eocyte tree

I met James (Jim) Lake for the first time more than 20 years ago but I had a chance to talk to him more recently in Chicago in 2013 [People I Met in Chicago at SMBE2013].

He became famous (infamous?) for challenging the Three Domain Hypothesis of Carl Woese (and friends) and for advocating better methods of constructing gene trees. Jim Lake proposed that eukaryote nuclei arose from within the archaebacterial clade and not as a sister groups of Archaea as the Three Domain Hypothesis claimed. The sister group was the "eocytes," represented at the time by Sulfolobus solfataricus, an archaebacterium that lives in hot springs (~80°C) and uses sulfur as a source of energy.

The origin of eukaryotes and the ring of life

The latest issue of Philosophical Transactions of the Royal Society B (Sept. 26, 2015) is devoted to Eukaryotic origins: progress and challenges. There are 16 articles and anyone interested in this subject has to read all of them.

Many (most) of you aren't going to do that so let me try and summarize the problem and the best current ideas on how to solve it. We begin with the introduction to the issue by the editors, Tom Williams, Martin Embley (Williams and Embly, 2015). Here's the abstract ...

Insulators, junk DNA, and more hype and misconceptions

The folks at Evolution News & Views (sic) can serve a very useful purpose. They are constantly scanning the scientific literature for any hint of evidence to support their claim about junk DNA. Recall that Intelligent Design Creationists have declared that if most of our genome is junk then intelligent design is falsified since one of the main predictions of intelligent design is that most of our genome will be functional.

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Genomes & Junk DNA
They must be getting worried because their most recent posts sounds quite desperate. The last one is: The Un-Junk Industry. It quotes a popular press report on a paper published recently in Procedings of the National Academy of Sciences (USA). The creationists concede that the paper itself doesn't even mention junk DNA but the article in EurekAlert does.

Razib Khan defends old-fashioned evolution theory

Razib Khan writes at Gene Expression. He's a big fan of personal genetics and genome sequencing and, in the past, has been a defender of the Modern Synthesis version of evolutionary theory. In light of the recent Nature discussion on "Does evolutionary theory need a rethink?" (Laland et al. 2014), Razib thought he would re-state his position [Evolution Ever Evolves].

I laid out my position in: Rethinking evolutionary theory. I don't think any of the new ideas like epigenetics, plasticity, facilitated variation etc. are about to change evolutionary theory significantly. However, I do think that the standard version of the 1940s Modern Synthesis was far too rigid and that a modern emphasis on population genetics (including Neutral Theory and more emphasis on random genetic drift) have significantly changed evolutionary theory—something close to a "revolution." The problem is that many scientists, and even many evolutionary biologists, haven't really integrated this change into their way of thinking. This resistance was very well described in a paper by Stephen J. Gould and Richard Lewontin over 45 year ago (Gould and Lewontin, 1978) [What Does San Marco Basilica Have to do with Evolution?]

I think there's already been a "revolution" but most people didn't notice and are still stuck in the 1940s adhering to an old-fashioned version of evolutionary theory that emphasizes adaptation.

Razib Khan doesn't like Gould and doesn't like new-fangled ideas like "neutralism" and "random genetic drift". Let's see what he thinks of the latest kerfluffle.

It seems that rather regularly there is a debate within evolutionary biology, or at least in public about evolutionary biology, where something new and bright and shiny is going to revolutionize the field. In general this does not pan out. I would argue there hasn’t been a true revolution in evolutionary biology since Mendelian genetics and classical Darwinism were fused in the 1920s and 1930s during the period when population genetics as a field was developed, and the famous "synthesis" developed out of the interaction of the geneticists with other domains of evolutionary relevance. This does not mean that there have not been pretenders to the throne. Richard Goldschmidt put forward his "hopeful monsters," neutralism reared its head in the 1970s, and evo-devo was all the rage in the 2000s. Developments that bore scientific fruit, such as neutralism, were integrated seamlessly into evolutionary biology, while those that did not, such as Goldschmidt’s saltationism fell by the wayside. This is how normal science works.

The main point here is whether Neutral Theory and an increased emphasis on random genetic drift "were integrated seamlessly" into the Modern Synthesis view that was popular in the 1960s. Is it true that the way modern population geneticists look at evolution is just a little bit different from the way evolutionary biologists thought about evolution in the 1920s, 1930s, and 1940s? I don't think so. I think there's been a significant shift—so much so that we can no longer refer to the "Modern Synthesis" as the most modern version of evolutionary theory.

Unlike Razib Khan, I am not convinced that most evolutionary biologists have made the shift. At my university, for example, the students must take a first-year course on evolution taught by members of the Dept. of Evolution & Ecology. I see these students in subsequent years and they don't understand the basics of population genetics. Nor do they appreciate the role of neutral alleles and random genetic drift. They are being taught the evolutionary theory of the Modern Synthesis (circa 1960).

Also the debates we are having over junk DNA suggests strongly that most scientists are not familiar with modern population genetics and Neutral Theory.

But every now and then you have a self-declared tribune of the plebs declaring that the revolution is nigh. For decades the late Stephen Jay Gould played this role to the hilt, decrying "ultra-Darwinism," and frankly misrepresenting the state of evolutionary theory to the masses from his perch as a great popularizer. More recently you have had more muted and conventional revisionists, such as Sean Carroll, who promote a variant of evo-devo that acclimates rather well to the climes of conventional evolutionary biology.

I do not believe that Gould misrepresented evolutionary theory to the masses. I believe that Richard Dawkins misrepresented evolutionary theory to the masses.

Like Razib, I'm not a big fan of evo-devo and I don't think it contributes much to fundamental evolutionary theory.

Nature now has a piece out which seems to herald the launching of another salvo in this forever war, Does evolutionary theory need a rethink? It’s written in the form of opposing dialogues. I’m very much in the camp of those believe that there’s no reason to overturn old terms and expectations. Evolutionary biology is advancing slowly but surely into new territory. There’s no problem to solve. The one major issue where I might have to make a stand is that it focusing on genetics is critical to understanding evolution, and dethroning inheritance from the center of the story would eviscerate the major thread driving the plot. The fact that evolutionary biologists have the conceptual and concrete gene as a discrete unit of information and inheritance which they can inspect is the critical fact which distinguishes them from fields which employ similar formalisms but have never made comparable advances (such as economics).

I agree with Razib Khan that genetics (population genetics) is the key to understanding evolutionary theory at the population level. I think we disagree on exactly what version of population genetics we support and on the importance of adaptation.

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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]

Laland, K., Uller, T., Feldman, M., Sterelny, K., Müller, G. B., Moczek, A., Jablonka, E., Odling-Smee, J., Wray, G. A., Hoekstra, H. E., Futuyma, D. J., Lenski, R. E., Mackay, T. F. C., Schluter, D. and Strassmann, J. E. (2014) Does evolutionary theory need a rethink? Nature 514, 163-165. [PDF]

Fixing CO2 fixation

How biochemistry students can become multi-millionaires by making plants more efficient. Has someone finally succeeded?

Living organisms need carbon to grow and divide. Many get their carbon atoms from organic molecules such as glucose or acetate that have been synthesized in other species.

Most organisms can fix carbon directly from carbon dioxide by a variety of different reactions but this isn't necessarily the primary source of carbon atoms. (We can fix carbon using pyruvate dehydrogenase, isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, and phosphoenolpyruvate carboxykinase (PEPCK) among others.)

What are lncRNAs?

Many genes encode proteins and many other genes specify functional RNAs that do not encode proteins. The "RNA genes" include the classic genes for ribosomal RNAs and tRNAs as well as genes for very well-studied RNAs that carry out catalytic roles in the cell. There are a myriad of small RNAs required for things like splicing and regulation. All species, both prokaryotes and eukaryotes, contain genes for a wide variety or functional RNAs.

Eukaryotes seem to have an abundance of genes for small RNAs that perform a number of specific roles in regulation etc. They also have a lot of DNA regions complementary to long noncoding RNAs or lncRNAs (also lincRNA). The definition of long noncoding RNAs seems arbitrary and ambiguous [see Long Noncoding RNA]. Some of them might even encode proteins!

As a general rule, these RNAs are longer than 200 bp and some scientists put the cutoff at 1000 bp. Simple eukaryotes, such as yeast, don't have a lot of lncRNAs but eukaryotes with large complex genomes that are full of junk DNA seem to have a lot of different lncRNAs. The DNA regions¹ that specify these lncRNAs ar not conserved. This strongly suggest that many of the lncRNAs are spurious nonfunctional transcripts even though some of them have well-characteized functions [see On the function of lincRNAs].

As usual, we have a definition problem. Are "lncRNAs" just a generic class of long noncoding RNAs that include thousands of nonfunctional molecules that are nothing more than junk RNA? Or, does the term "lncRNA" refer only to the subset that has a function? If it's the latter, then we should probably be referring to "putative" lncRNAs most of the time since the vast majority have not been shown to have a function. (There are about 10,000 of these RNAs in humans.)

I don't see how you can avoid the elephant in the room whenever you talk about lncRNAs. The most important question in NOT whether some of them have a function—that was demonstrated 30 years ago. The important question is whether the majority, or even a substantial minority, have a function.

That's why I was eager to read a short review by Rinn and Guttman in a recent issue of Science (Rinn and Guttman, 2014). They describe two lncRNAs that probably play a role in organizing chromatin within the nucleus (Xist and Neat1, both fram mammals). That's cool.

Then they say,

Collectively, these studies suggest that lncRNAs may shape nuclear organization by using the spatial proximity of their transcription locus as a means to target preexisting local neighborhoods. lncRNAs can in turn modify and reshape the organization of these local neighborhoods to establish new nuclear domains by interacting with various protein complexes, including chromatin regulators. Once established, a lncRNA can act to maintain these nuclear domains through active transcription and recruitment of interacting proteins to these domains. While the mechanism for how lncRNAs establish these domains is not fully understood, it is becoming increasingly clear that lncRNAs are important at all levels of nuclear organization—exploiting, driving, and maintaining nuclear compartmentalization.

It sure sounds like they are describing a particular function (nuclear organization) to the majority of lncRNAs. But what if 90% of all 10,000 lncRNAs have no function and what if only 100 of the remaining functional lncRNAs are involved in nuclear organization? That means there are 900 functional lncRNAs that play a different role in the cell?

If that were true, you would write that last paragraph very differently. If you recognize the elephant, you might say something like this ....

Very few lncRNAs have been shown to have a function and there's a very good chance that most of them are spurious transcripts that have no function. However, a small percentage do seem to have a function. In this review we have identified some long noncoding RNAs that appear to be involved in nuclear organization. We propose to call these RNAs "noRNAs" for "nuclear organizer RNAs" on the grounds that once a function has been identified we should stop referring to them as lncRNAs.

But that doesn't sound nearly as exciting as the subtitle of the article, "Long noncoding RNAs may function as organizing factors that shape the cell nucleus" or the quotation that's prominently displayed in a box in the center of the page, "... it is becoming increasingly clear that IncRNAs are important in all levels of nuclear organization—exploiting, driving, and maintaining nuclear compartmentalization." When did science become so dedicated to hype over substance? I must have missed the memo.

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1. I use "DNA regions" instead of "genes" because the definition of a gene requires that the gene product be functional. You can't call them genes unless you have demonstrated that the RNA has a function.

Rinn, J. and Guttman, M. (2014) RNA and dynamic nuclear organization. Science 345"1240-1241 [doi: 10.1126/science.1252966]

Michael Behe's final thoughts on the edge of evolution

We've been having an interesting discussion about chloroquine resistance and the Edge of Evolution. It began last month when Michael Behe started bragging that his "prediction" had been confirmed by a recent paper [A Key Inference of The Edge of Evolution Has Now Been Experimentally Confirmed]. It didn't take long for Casey Luskin to jump on the bandwagon [So, Michael Behe Was Right After All; What Will the Critics Say Now?]. Luskin demanded an apology from Behe;s critics.

It turns out that Behe and Luskin are wrong and the recent results published by Summers et al. (2014) actually refute most of Micheal Behe's calculations. PZ Myers pointed out that Behe's critics were mostly¹ right when they criticized the original calculations in The Edge of Evolution [Quote-mined by Casey Luskin!].

How many genes do we have and what happened to the orphans?

How many genes in the human genome? There's only one correct answer to that question and that's "we don't know."

The main problem is counting the number of genes that produce functional RNA molecules. The latest Ensembl results are based on build CRch37 from February 2009 and the GENCODE annotation from last year (GENCODE 19) [see Human assembly and gene annotation and Harrow et al., 2014]

The most recent estimates are 20,807 protein-encoding genes, 9,096 genes for short RNAs, and 13,870 genes for long RNAs. This gives 43,773 genes. Nobody knows for sure how many of the putative genes for RNAs actually exist. They may only be a few thousand functional genes in this category.

It's a lot easier to figure out whether a gene really encodes a functional protein so most of the annotation effort is focused on those genes. I want to draw your attention to a recent paper by Ezkurdia et al. (2014) that discusses this issue. The authors begin with a bit of history ...

ASBMB Core Concepts in Biochemistry and Molecular Biology: Molecular Structure and Function

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Better BiochemistryThe American Society for Biochemistry and Molecular Biology (ASBMB) has decided that the best way to teach undergraduate biochemistry is to concentrate on fundamental principles rather than facts and details. This is an admirable goal—one that I strongly support.

Over the past few months, I've been discussing the core concepts proposed by Tansey et al. (2013) [see Fundamental Concepts in Biochemistry and Molecular Biology]. The five concepts are:

1. evolution [ASBMB Core Concepts in Biochemistry and Molecular Biology: Evolution ]
2. matter and energy transformation [ASBMB Core Concepts in Biochemistry and Molecular Biology: Matter and Energy Transformation]
3. homeostasis [ASBMB Core Concepts in Biochemistry and Molecular Biology: Homeostasis]
4. biological information [ASBMB Core Concepts in Biochemistry and Molecular Biology: Biological Information]
5. macromolecular structure and function [ASBMB Core Concepts in Biochemistry and Molecular Biology: Molecular Structure and Function]

Alan Sokal explains the scientific worldview

As most of you know, I prefer a broad definition of science as a way of knowing. I usually refer to it as a way of knowing based on rational thinking, evidence, and healthy skepticism but there are many other ways of expressing the same idea.

However you say it, the broad definition of the scientific way of knowing covers everything, not just physics, biology, chemistry and geology. Not only that, it appears to be the only way of knowing that has proven to be successful. Thus, I can tentatively conclude that it is the only way of knowing until someone provides an example of knowledge obtained by another way of knowing.

Alan Sokel has posted three articles on Massimo Pigliucci new blog, Scientia Salon [What is science and why should we care? — Part III].

Here's how he describes science in Part III.

We have now travelled a long way from “science,” understood narrowly as physics, chemistry, biology and the like. But the whole point is that any such narrow definition of science is misguided. We live in a single real world; the administrative divisions used for convenience in our universities do not in fact correspond to any natural philosophical boundaries. It makes no sense to use one set of standards of evidence in physics, chemistry and biology, and then suddenly relax your standards when it comes to medicine, religion or politics. Lest this sound to you like a scientist’s imperialism, I want to stress that it is exactly the contrary. As the philosopher Susan Haack lucidly observes:

“Our standards of what constitutes good, honest, thorough inquiry and what constitutes good, strong, supportive evidence are not internal to science. In judging where science has succeeded and where it has failed, in what areas and at what times it has done better and in what worse, we are appealing to the standards by which we judge the solidity of empirical beliefs, or the rigor and thoroughness of empirical inquiry, generally.” [21]

The bottom line is that science is not merely a bag of clever tricks that turn out to be useful in investigating some arcane questions about the inanimate and biological worlds. Rather, the natural sciences are nothing more or less than one particular application — albeit an unusually successful one — of a more general rationalist worldview, centered on the modest insistence that empirical claims must be substantiated by empirical evidence.

Conversely, the philosophical lessons learned from four centuries of work in the natural sciences can be of real value — if properly understood — in other domains of human life. Of course, I am not suggesting that historians or policy-makers should use exactly the same methods as physicists — that would be absurd. But neither do biologists use precisely the same methods as physicists; nor, for that matter, do biochemists use the same methods as ecologists, or solid-state physicists as elementary-particle physicists. The detailed methods of inquiry must of course be adapted to the subject matter at hand. What remains unchanged in all areas of life, however, is the underlying philosophy: namely, to constrain our theories as strongly as possible by empirical evidence, and to modify or reject those theories that fail to conform to the evidence. That is what I mean by the scientific worldview.

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Hat Tip: Jerry Coyne: Alan Sokal highlights the incompatibility of science and religion

Why does Stephen H. Webb use the word "Darwinism"?

We know why the IDiots use the words "Darwinist" and "Darwinism" to describe evolutionary biologists and modern evolutionary theory. There are three main reasons.

1. They want their flocks to believe that modern scientists worship Charles Darwin and his 150 year-old theory so that when they discredit him—as they are constantly trying to do—it reflects on evolution.
2. They want to link modern evolutionary biology to social Darwinism and it's easier to do so if they refer to evolutionary biologists as Darwinists.
3. They are too stupid to realize that there's a lot more to modern evolutionary biology than natural selection.

Every time you challenge creationists on this point they find some way to defend their use of Darwinism rather than just say "evolutionary biology" or "modern evolutionary theory." There's a reason for this (see above).

Stephen H. Webb is the latest example. Apparently his use of "Darwinism" was challenged so he wrote a blog post on Evolution News & Views (sic) defending it The Strange Mental World of Darwinian Fundamentalists. I hope you appreciate the irony in the title.

The crystal structure of E. coli RNA polymearse σ70 holoenzyme

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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.

Territorial demarcation and the meaning of science

Massimo Pigliucci doesn't get enough respect. He's upset by the "New Atheists" who place a great deal of emphasis on the scientific way of knowing and demand evidence that any other way of knowing is successful. These mean New Atheists (I count myself as one of them) use a very broad definition of science that includes most of the admirable activities of philosophers. Pigliucci is mostly a philosopher and he doesn't think that philosophy is getting enough respect from the New Atheists.

Here's the cartoon he published on his blog to illustrate the problem [see Rationally Speaking cartoon: Sam Harris].

What do they mean when they say they want to extend the Modern Synthesis?

As far as I'm concerned, the "Modern Synthesis" has been replaced by modern evolutionary theory that incorporates Nearly-Neutral Theory and random genetic drift as an important mechanism of evolution [see Is the "Modern Synthesis" effectively dead? ]. This extension, and replacement, of the 1940s version of evolutionary theory took place in mainly in the 1970s.

If I'm correct, then why all the fuss in the 21st century about extending the Modern Synthesis?

I think there are two things going on here. First, there are a bunch of biologists who want to incorporate their favorite fad into modern evolutionary theory. They think that their ideas are so revolutionary that this requires an extensive revision of evolutionary theory. Second, those biologists seem to have been asleep during the 1970s when the Modern Synthesis died so they are fighting a strawman.

Vertebrate Complexity Is Explained by the Evolution of Long-Range Interactions that Regulate Transcription?

The Deflated Ego Problem is a very serious problem in molecular biology. It refers to the fact that many molecular biologists were puzzled and upset to learn that humans have about the same number of genes as all other multicellular eukaryotes. The "problem" is often introduced by stating that the experts working on the human genome project expected at least 100,000 genes but were "shocked' when the first draft of the human genome showed only 30,000 genes (now down to about 25,000). This story is a myth as I document in: Facts and Myths Concerning the Historical Estimates of the Number of Genes in the Human Genome. Truth is, most knowledgeable experts expected that humans would have about the same number of genes as other animals. They realized that the differences between fruit flies and humans, for example, didn't depend on a host of new human genes but on the timing and expression of a mostly common set of genes.

This isn't good enough for many human chauvinists. They are still looking for something special that sets human apart from all other animals. I listed seven possibilities in my post on the deflated ego problem:

Science Doesn't Have All the Answers but Does It Have All the Questions?

Jerry Coyne has been following the debate between Steven Pinker and Leon Wieseltier on the topic of scientism [see The final round: Pinker vs. Wieseltier on scientism]. Jerry seems to agree with both Pinker and Wieseltier that there are "two magisteria" (science and humanities) ...

[Wieseltier] calls for a “two magisteria” solution, with science and humanities kept separate, but with “porous boundaries.” But that is exactly what Pinker called for, too! Wieseltier claims that Pinker and other advocates of scientism advocate “totalistic aspirations,” i.e., the complete takeover of humanities by the sciences (“unified field theories,” Wieseltier calls them), but Pinker explicitly said that he wasn’t calling for that.

...

As you can see above, Steve never argued that science is, or should be, supreme in all the contexts. Indeed, in his earlier piece he noted that art and literature, while they might be informed in some ways by science, nevertheless have benefits independent of science. To me, those benefits include affirming our common humanity, being moved by the plight of others, even if fictional, and luxuriating in the sheer beauty of music, words, or painting. (Note, though, that one day science might at least explain why we apprehend that beauty.)

I'm not sure how Pinker, Wieseltier, and Coyne are defining science but it's clear that they aren't using the same definition I use.

I think that science is a way of knowing based on evidence and logic and healthy skepticism. I think that all disciplines seeking knowledge use the scientific approach. This is the broad definition of science used by many philosophers and scientists.

Maarten Boudry discusses, and accepts, this definition in his chapter on "Loki's Wager and Lauden's Error" in Philosophy of Pseudescience: Reconsidering the Demarcation Problem. Boudry says that the distinction between the ways of knowing used by biologists, philosophers, and historians are meaningless and there's no easy way to distinguish them (territorial demarcation). On the other hand, there is a way to distinguish between good scientific reasoning and bad scientific reasoning like Holocaust denial.

I have expressed little confidence in the viability of the territorial demarcation problem, and even less interest in solving it. Not only is there no clear-cut way to disentangle epistemic domains like science and philosophy, but such a distinction carries little epistemic weight. The demarcation problem that deserves our attention is the one between science and pseudoscience (and the analogous ones between philosophy and pseudophilosophy and between history and pseudohistory).

Sven Ove Hanson is more specific because he actually defines "science in a broad sense" in a way that I have been using it for several decades. This is from his chapter on "Defining Pseudoscience and Science" in Philosophy of Pseudescience: Reconsidering the Demarcation Problem.

Unfortunately neither "science" nor any other established term in the English language covers all the disciplines that are parts of this community of knowledge disciplines. For lack of a better term, I will call them "science(s) in the broad sense." (The German word "Wissenschaft," the closest translation of "science" into that language, has this wider meaning; that is, it includes all the academic specialties, including the humanities. So does the Latin "scientia.") Science in a broad sense seeks knowledge about nature (natural science), about ourselves (psychology and medicine), about our societies (social science and history), about our physical constructions (technological science), and about our thought construction (linguistics, literary studies, mathematics, and philosophy). (Philosophy, of course, is a science in this broad sense of the word.)

If this is what we mean by science" then there's no difference between the ways we try to acquire knowledge in the humanities or the natural sciences and the debate between Pinker and Wieseltier takes on an entirely different meaning.

There aren't "two magisteria" but only one. Unless, of course, someone is willing to propose a successful non-scientific way of knowing. I have asked repeatedly for examples of knowledge ("truth") that have been successfully acquired by any other way of knowing. So far, nobody has come up with an answer so we can tentatively conclude that science (in the broad sense) is the only valid way of acquiring true knowledge.

Clearly we don't have all the answers to everything so it's clear that neither science nor anything else has all the answers. What about the questions? Are there any knowledge questions that science (in the broad sense) can't address? I don't think there are. I think "science" covers all the questions even though it doesn't (yet) have all the answers.

If this is "scientism" then I'm guilty. What is the alternative? Is it revelation (revealed truth)? Or is there some other way of knowing that I haven't heard about?

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The Dark Matter Rises

John Mattick is a Professor and research scientist at the Garvan Institute of Medical Research at the University of New South Wales (Australia).

John Mattick publishes lots of papers. Most of them are directed toward proving that almost all of the human genome is functional. I want to remind you of some of the things that John Mattick has said in the past so you'll be prepared to appreciate my next post [The Junk DNA Controversy: John Mattick Defends Design].

Mattick believes that the Central Dogma means DNA makes RNA makes protein. He believes that scientists in the past took this very literally and discounted the importance of RNA. According to Mattick, scientists in the past believed that genes were the only functional part of the genome and that all genes encoded proteins.

If that sounds familiar it's because there are many IDiots who make the same false claim. Like Mattick, they don't understand the Central Dogma of Molecular Biology and they don't understand the history that they are distorting.

Mattick believes that there is a correlation between the amount of noncoding DNA in a genome and the complexity of the organism. He thinks that the noncoding DNA is responsible for making tons of regulatory RNAs and for regulating expression of the genes. This belief led him to publish a famous figure (left) in Scientific American.

Mattick has many followers. So many, in fact, that the Human Genome Organization (HUGO) recently gave him an award for his contributions to the study of the human genome. Here's the citation.
Theme
Genomes
& Junk DNA

The Award Reviewing Committee commented that Professor Mattick’s “work on long non-coding RNA has dramatically changed our concept of 95% of our genome”, and that he has been a “true visionary in his field; he has demonstrated an extraordinary degree of perseverance and ingenuity in gradually proving his hypothesis over the course of 18 years.”

Let's see what this "true visionary" is saying this year. The first paper is "The dark matter rises: the expanding world of regulatory RNAs" (Clark et al., 2013). Here's the abstract ...

The ability to sequence genomes and characterize their products has begun to reveal the central role for regulatory RNAs in biology, especially in complex organisms. It is now evident that the human genome contains not only protein-coding genes, but also tens of thousands of non–protein coding genes that express small and long ncRNAs (non-coding RNAs). Rapid progress in characterizing these ncRNAs has identified a diverse range of subclasses, which vary widely in size, sequence and mechanism-of-action, but share a common functional theme of regulating gene expression. ncRNAs play a crucial role in many cellular pathways, including the differentiation and development of cells and organs and, when mis-regulated, in a number of diseases. Increasing evidence suggests that these RNAs are a major area of evolutionary innovation and play an important role in determining phenotypic diversity in animals.

This is his main theme. Mattick believes that a large percentage of the human genome is devoted to making regulatory RNAs that control development. He believes that the evolution of this complex regulatory network is responsible for the creation of complex organisms like humans, which, incidentally, are the pinnicle of evolution according to the figure shown above.

The second paper I want to highlight focuses on a slightly different theme. It's title is "Understanding the regulatory and transcriptional complexity of the genome through structure." (Mercer and Mattick, 2013). In this paper he emphasizes the role of noncoding DNA in creating a complicated three-dimensional chromatin structure within the nucleus. This structure is important in regulating gene expression in complex organisms. Here's the abstract ...

An expansive functionality and complexity has been ascribed to the majority of the human genome that was unanticipated at the outset of the draft sequence and assembly a decade ago. We are now faced with the challenge of integrating and interpreting this complexity in order to achieve a coherent view of genome biology. We argue that the linear representation of the genome exacerbates this complexity and an understanding of its three-dimensional structure is central to interpreting the regulatory and transcriptional architecture of the genome. Chromatin conformation capture techniques and high-resolution microscopy have afforded an emergent global view of genome structure within the nucleus. Chromosomes fold into complex, territorialized three-dimensional domains in concert with specialized subnuclear bodies that harbor concentrations of transcription and splicing machinery. The signature of these folds is retained within the layered regulatory landscapes annotated by chromatin immunoprecipitation, and we propose that genome contacts are reflected in the organization and expression of interweaved networks of overlapping coding and noncoding transcripts. This pervasive impact of genome structure favors a preeminent role for the nucleoskeleton and RNA in regulating gene expression by organizing these folds and contacts. Accordingly, we propose that the local and global three-dimensional structure of the genome provides a consistent, integrated, and intuitive framework for interpreting and understanding the regulatory and transcriptional complexity of the human genome.

Other posts about John Mattick.

How Not to Do Science
John Mattick on the Importance of Non-coding RNA
John Mattick Wins Chen Award for Distinguished Academic Achievement in Human Genetic and Genomic Research
International team cracks mammalian gene control code
Greg Laden Gets Suckered by John Mattick
How Much Junk in the Human Genome?
Genome Size, Complexity, and the C-Value Paradox

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Clark, M.B., Choudhary, A., Smith, M.A., Taft, R.J. and Mattick, J.S. (2013) The dark matter rises: the expanding world of regulatory RNAs. Essays in Biochemistry 54:1-16. [doi:10.1042/bse0540001]

Mercer, T.R. and Mattick, J.S. (2013) Understanding the regulatory and transcriptional complexity of the genome through structure. Genome research 23:1081-1088 [doi: 10.1101/gr.156612.113]

What Should We Teach About the "Tree of Life"?

As most of you already know, I think the Three Domain Hypothesis is dead. The history of life is better explained as a net with rampant transfer of genes between species [The Web of Life]. This idea has been widely promoted by Ford Doolittle.

The debate over the tree of life has implications concerning the distinction between "prokaryote" and "eukaryote." I was checking some recent papers and came across one by Doolittle and Zhaxybayeva (2013) that seems particularly relevant. They discuss the evidence for and against the division of life into three domains and the attempt by Norm Pace to ban the word "prokaryote."

The authors point out, once again, that eukaryotic genes are most closely related to genes from cyanobacteria, proteobacteria, and archaebacteria, in that order. The majority, by far, have their closest homologs in bacteria, not archaebacteria. The most likely explanation is that euakryotes are chimeras resulting from fusion of an archaebacterium and a eubacterium plus genes transferred from mitochondria and chloroplast to the nuclear genome.

The Trouble with Scientism?

Philip Kitcher is a philosopher who specializes in the philsophy of science. He is a professor at Columbia University in New York, USA. He's well known in the atheist, skeptical community and he's an outspoken critic of creationism.

He just published an article in The New Republic entitled: The Trouble with Scientism: Why history and the humanities are also a form of knowledge.

Many of the debates on the issue of "scientism" depend on how you define "science." As you can see from the subtitle of his essay, it's about the two cultures. Kitcher separate the search for knowledge in the humanities from the search for knowledge in the natural sciences. Here's what he says ...

It is so easy to underrate the impact of the humanities and of the arts. Too many people, some of whom should know better, do it all the time. But understanding why the natural sciences are regarded as the gold standard for human knowledge is not hard. When molecular biologists are able to insert fragments of DNA into bacteria and turn the organisms into factories for churning out medically valuable substances, and when fundamental physics can predict the results of experiments with a precision comparable to measuring the distance across North America to within the thickness of a human hair, their achievements compel respect, and even awe. To derive one’s notion of human knowledge from the most striking accomplishments of the natural sciences easily generates a conviction that other forms of inquiry simply do not measure up. Their accomplishments can come to seem inferior, even worthless, at least until the day when these domains are absorbed within the scope of “real science.”

It's clear the he thinks of "science" as something that only natural scientists do. This is a different definition that the one I prefer. I think of "science" as a way of knowing that involves evidence, skepticism, and rationalism. I agree with Rush Holt [Rush Holt on Science and Critical Thinking] that critical thinking is an important part of science as a way of knowing and I agree with him that the scientific approach can be used everywhere—even in philosophy departments.

Kitcher's view is different. That leads him to define scientism as ...

The problem with scientism—which is of course not the same thing as science—is owed to a number of sources, and they deserve critical scrutiny. The enthusiasm for natural scientific imperialism rests on five observations. First, there is the sense that the humanities and social sciences are doomed to deliver a seemingly directionless sequence of theories and explanations, with no promise of additive progress. Second, there is the contrasting record of extraordinary success in some areas of natural science. Third, there is the explicit articulation of technique and method in the natural sciences, which fosters the conviction that natural scientists are able to acquire and combine evidence in particularly rigorous ways. Fourth, there is the perception that humanists and social scientists are only able to reason cogently when they confine themselves to conclusions of limited generality: insofar as they aim at significant—general—conclusions, their methods and their evidence are unrigorous. Finally, there is the commonplace perception that the humanities and social sciences have been dominated, for long periods of their histories, by spectacularly false theories, grand doctrines that enjoy enormous popularity until fashion changes, as their glaring shortcomings are disclosed.

That's a really stupid definition of scientism. I don't know anyone who actually thinks like that. Do you know any "natural science imperialists" who dismiss the humanities and the social sciences?¹

I believe that people in the humanities and social sciences use the same approach as those in the natural sciences. I call that way of knowing "science" but if someone wants to come up with a better name, I'm all ears. As far as I'm concerned, science (as I define it) is the ONLY way of knowing that has actually been successful in discovering true knowledge. I guess that makes me guilty of "scientism."

It's very easy to refute scientism as I define it. All you have to do is show that there's some other way of knowing that produces universal truths or true knowledge. Perhaps philosophers have discovered truths using some other way of knowing?

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1. I criticize evolutionary psychology. The reason why I'm so critical is precisely because they don't conform to the scientific way of knowing. They are not doing "good science" by any definition of the word "science."