Deflated egos and the G-value paradox

The Deflated Ego Problem refers to the fact that many scientists were very disappointed to learn we had less than 30,000 genes. Those scientists were expecting that the human genome would contain many more genes in line with their belief that humans must be genetically more complex than the "lower" animals. They should have known better since knowledgeable experts were predicting fewer than 30,000 genes and these same experts knew that humans don't need many more genes than other animals [see: Revisiting the deflated ego problem].

Disappointed scientists don't use the term "deflated ego;" instead they refer to their problem as the G-value paradox. This makes it seem like a real problem instead of just a mistaken view of evolution.

Michael Behe's third book

I'm looking forward to Michael Behe's third book, which is due to be published in February. As most of you probably know, Michael Behe is a biochemist and a former professor at Lehigh University in Scranton, Pennsylvania, USA. He's also a senior fellow at the Discovery Institute’s Center for Science & Culture—the most prominent organization pushing Intelligent Design Creationism.

This will be Behe's third book. The first one was Darwin's Black Box (1996) where he argued against evolution by suggesting that some cellular complexes (e.g. bacterial flagella) are irreducibly complex and could not possibly have evolved by natural means. His second book was The Edge of Evolution (2007) where the theme was that there are limits to evolution preventing it from accomplishing significant beneficial changes.

Latest Tango in Halifax

I've known Yana Eglit for many years. She frequently posts comments on this blog but you won't recognize her name because she uses a pseudonym.¹ Yana is a graduate student in the lab of Alastair Simpson at Dalhousie University in Halifax, Nova Scotia, Canada. A few years ago she saw some strange organisms dancing in a Petri dish.²

The microorganisms belong to the group Hemimastigophora. Yana found them in a clump of dirt she picked up while hiking near Halifax. They named the species Hemimastix kukwesjijk. The group only contains a few other species.

Hemimastigophora is one of those protist groups that have been difficult to classify and difficult to place relative to other protists. It's traditionally been given the status of a phylum but its position in the eukaryotic tree was ambiguous.

The Simpson lab, in a collaboration with Andrew Roger's group, sequenced a number of genes (transcripts) from H. kukwesjijk and another species that they recently identified (Spirenema). The datasets contained samples of about 300 genes of each species. Trees constructed with this dataset place the Hemimastigophora near the base of the eukrayotic tree as a sister group to Diaphoretices. The work was published in a recent issue of Nature (Lax, Egrit, et al., 2018).

The details of eukaryotic taxonomy and the various subdivisions needn't concern us but the important take-home lesson is that there are a huge number of protists forming diverse groups that separated more than a billion years ago. The authors claim that Hemimastigophora deserves supra-kingdom status equivalent to the other supra-kingdoms shown in the figure (modified from Figure 4 of the paper).

The root of the eukaryotic tree is controversial. It could be at positions a, b, or c, shown in the figure. According to the authors, position a is the most favored these days. Regardless of where the root is actually placed, the new positioning of Hemimastigophora adds a lot of information to the deepest parts of the eukaryotic tree and brings us closer to identifying the most primitive features of the eukaryotic cell.

I wonder how many other strange species can be found in Canadian dirt?

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Photo Credit: The photo of Yana Eglit at her microscope is from the Dalhousie University press office [Hidden in plain sight: Dal evolutionary biologists uncover a new branch on the Tree of Life]

1. Which she might accidentally reveal if she responds to this post!

2. The fact they were "dancing" gave me an excuse to use a corny title that refers to one of our favorite TV shows, "Last Tango in Halifax."

Lax, G., Eglit, Y., Eme, L., Bertrand, E. M., Roger, A. J., and Simpson, A. G. B. (2018) Hemimastigophora is a novel supra-kingdom-level lineage of eukaryotes. Nature. (in press) [doi: 10.1038/s41586-018-0708-8]

Revisiting the deflated ego problem

Humans are just another animal. All animals share a core set of several thousand genes and all mammals have about the same number of homologous genes (~25,000). The differences between species such as gorillas, bats and whales are due almost exclusively to differences in the timing of expression of these common genes.

This concept is not new. It was the major theme of Stephen Jay Gould's book, Ontogeny and Phylogeny, back in 1977 [Learning About EVO-Devo]. Over the next twenty years or so, the concept was confirmed repeatedly by the work of hundreds of developmental biology labs working mostly with model organisms such as Drosophila (fruit flies). The field is evolutionary developmental biology or "evo-devo" and that work has been nicely summarized in several popular books appearing in the 21st century.

Celebrating 50 years of Neutral Theory

The importance of Neutral Theory and Nearly-Neutral Theory cannot be exaggerated. It has radically transformed the way experts think about evolution, especially at the molecular level. Unfortunately, the average scientist is not aware of the revolution that took place 50 years ago and they still think of evolution as a synonym for natural selection. I suspect that 80% of biology undergraduates in North American universities are graduating without a deep understanding of the importance of Neutral Theory.¹

The journal of Molecular Biology and Evolution has published a special issue: Celebrating 50 years of the Neutral Theory. The key paper published 50 years ago was Motoo Kimura's paper on “Evolutionary rate at the molecular level” (Kimura, 1968) followed shortly after by a paper from Jack Lester King and Thomas Jukes on "Non-Darwinian Evolution" (King and Jukes, 1969).

The special issue contains reprints of two classic papers published in Molecular Biology and Evolution in 1983 and 2005. In addition, there are 14 reviews and opinions written by editors of the journal and published earlier this year (see below). It's interesting that several of the editors of a leading molecular evolution journal are challenging the importance of Neutral Theory and one of them (senior editor Matthew Hahn) is downright hostile.

DNA Is Not Destiny by Steven J. Heine

DNA Is Not Destiny: The Remarkable Completely Misunderstood Relationship between You and Your Genes
by Steven J. Heine
W.W. Norton & Company, New York/London (2017)
ISBN: 978-0-393-24408-3

Steven Heine is a Professor in the Department of Psychology at the University of British Columbia (Vancouver, B.C., Canada). He has written a book about the perils of DNA testing and his main thesis is that the results of such tests are bound to make you fell unhappy because you will learn that you have a higher risk of several nasty diseases. He warns us that the science behind these predictions is not nearly as solid as the testing companies would have you believe but his main point is the psychological impact of the test results. He claims that we are not conditioned to put the results into the proper perspective because we are pre-conditioned to adopt a very fatalist view of our genetic makeup.

He had his DNA analyzed by a number of companies. Here's some of what he learned from 23 and Me.

23andMe provided me with a gripping set of predictions about my health with real concrete numbers—I learned that I have a 2.1 percent chance of developing Parkinson's disease, and this is 32 percent higher than the average person. The 23andMe experience "felt" satisfying because it provided a wealth of highly specific and personal information about my health. But then, so would the fortune-teller down the street, and at least she isn't claiming any scientific foundation to her predictions.

The role of chance in evolution

I highly recommend this brief editorial by Naruya Saitou: "Chance, Finiteness, and History" (Saitou, 2018). Saitou is a strong proponent of Neutral Theory and the importance of random genetic drift. Together these influences, along with the "random" nature of mutation, introduce a major element of chance and accident into evolution.

Saitou was a student of Masatochi Nei and he recounts how he was influenced by Nei's 1987 book "Molecular Evolutionary Genetics." I remember reading that book 30 years ago and being very impressed with Nei's case for mutationism. Dan Graur also studied with Nei and he was kind enough to introduce me to Nei a few years ago in Chicago.

I think it's very clear that the role of chance in evolution, especially in molecular evolution, is very much underappreciated by the average scientist and by almost all non-scientists who are interested in the field. I doubt they will be convinced by a short essay but at least it will alert them to a different way of thinking.

Here's an example from Saitou's essay of that way of thinking ...

This world is finite. Our earth is just a 40,000-km circumference sphere. Life evolved on this tiny planet. We have to face the finiteness of the living world when we think about evolution. Random fluctuation of DNA copies (allele frequencies in classic sense) is a logical consequence of this finiteness. Because evolution follows time, evolution is historical. And chance played an important role in evolutionary history, as already noted by Darwin (1859). This is why I often mention three words—chance, finiteness, and history—in my talks and books as well as the title for this perspective.

Saitou is using "evolution" in two different senses. First, there's the ongoing process involving changes in allele frequencies and then there's the history of life. I think it's best to avoid using the word "evolution" as a stand-in for the history of life but that's just a quibble. The idea behind the history of life is that the pathway that each extant lineage has followed over the past three billion years is very much due to chance and accident. It's like Gould's idea that the tape of life can't be replayed.

The essay contains a sentence about junk DNA ...

From direct comparison of protein or RNA coding gene regions with noncoding regions of many genomes, it became clear that the majority of intergenic regions and introns are in fact “junk” DNA, as predicted by Ohno (1972).

This is about all the comment that's needed if you're a population geneticist. From their perspective, the debate is over and junk DNA won decisively over the speculation that most of our genome is functional. I wish more scientists, journalists, and philosophers would realize that the leading experts have reached a consensus on this subject.¹

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1. Let me repeat what I've said many times before: you don't have to agree with the views of these experts but you do have to acknowledge what you are up against when you argue for function. Do not mislead your audience by ignoring the experts in order to make your own opinion seem more reasonable.

Saitou, N. (2018) Chance, finiteness, and history. Molecular Biology and Evolution, 35(6), 1556-1557. [doi: 10.1093/molbev/msy087]

John Mattick's latest attack on junk DNA

John Mattick is the most prominent defender of the idea that the human genome is full of functional sequences. In fact, he is just about the only scientist of any prominence who's on that side of the debate. His main "evidence" is the fact that genomes are pervasively transcribed and that most of the transcripts are functional. Let's look at his latest review paper to see how well this argument stands up to close scrutiny (Mattick, 2018).¹

As you read this post, keep in mind that in 2012 John Mattick was awarded a prize by the Human Genome Organization for proving his hypothesis [John Mattick Wins Chen Award for Distinguished Academic Achievement in Human Genetic and Genomic Research].

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.”

Mattick follows his usual format by giving us his version of history. He has argued for the past 15 years that the scientific community has been reluctant to accept the evidence of massive amounts of regulatory RNA genes because it conflicts with the standard paradigm of the supremacy of proteins. In the past he has claimed that this paradigm is based on the Central Dogma which states, according to him, that the only real function of DNA is to make proteins [How Much Junk in the Human Genome?]. As we shall see, he hasn't abandoned that argument but at least he no longer refers to the Central Dogma for support

The great junk DNA debate

I've been talking to philosophers lately about the true state of the junk DNA controversy. I imagine what it would be like to stage a great debate on the topic. It's easy to come up with names for the pro-junk side; Dan Graur, Ford Doolittle, Sean Eddy, Ryan Gregory etc. It's hard to think of any experts who could defend the idea that most of our genome is functional. The only scientist I can think of who would accept such a challenge is John Mattick but let's imagine that he could find three others to join him in the great debate.

I claim that the debate would be a rout for the pro-junk side. The data and the theories are all on the side of those who would argue that 90% of our genome is junk. I don't think the functionalists could possibly defend the idea that most of our genome is functional. What do you think?

Assuming that I'm right, why is it that the average scientist doesn't know this? Why do they still believe there's a good case for function when none of the arguments stand up to close scrutiny? And why are philosophers not conveying the true state of the controversy to their readers? I'm told that anti-junk philosophers like Evelyn Fox Keller are held in high regard even though her arguments are easy to refute [When philosophers talk about genomes]. I'm told that John Mattick is highly respected in philosophy circles even though knowledgeable scientists have little use for his writings.

Can readers help me identify papers by philosophers of science that come down on the side of junk DNA and conclude that experts like Graur, Doolittle, etc are almost certainly correct?

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Image Credit: The cartoon is by Tom Gauld and it was published online at the The New York Times Magazine website. I hope they will consider it fair use on an educational blog. See: Junk DNA comments in the New York Times Magazine.

Alternative splicing and the gene concept

I just learned about a workshop scheduled for the end of this month. The topic is: Evolutionary Roles of Transposable Elements and Non-coding DNA: The Science and the Philosophy.

I'd love to attend but it's a just small workshop designed to encourage dialogue between scientists and philosophers who are interested in the topic. Here's a list of the speakers ...

• Ryan Gregory: Junk DNA, genome size, and the onion test.
• Stefan Linquist: Four decades debating junk DNA and the Phenotype Paradigm is (somehow) alive and well.
• Chris Ponting: 92.9% of the human genome evolved neutrally.
• Paul Griffiths: Both adaptation and adaptivity are relevant to diagnosing function.
• Ford Doolittle: Selfish genes and selfish DNA: is there a difference?
• Justin Garson: Biological functions, the liberality problem, and transposable elements.
• Joyce Havstad: Evolutionary Thinking about Critique of Function Talk.
• Guillame Bourque: Impact of transposable elements on human gene regulatory networks.
• Ulrich Stegman: On parity, genetic causation and coding.
• Steven Downes: Understanding non-coding variants as disease risk alleles.
• Alexander Palazzo: How nuclear retention and cytoplasmic export of RNAs reduces the deleteriousness of junk DNA.
• David Haig: Pax somatica
• Cedric Feschotte: Transposable elements as catalysts of genome evolution.

Who wants "A Sad Case: Owen vs Huxley" pamphlet and a possible Darwin letter?

A friend has a neighbor who's in possession of a pamphlet from 1863 on the Owen vs Huxley debate. The text of the pamphlet is here: A Report of A SAD CASE, Recently tried before the Lord Mayor, OWEN versus HUXLEY, In which will be found fully given the Merits of the great Recent BONE CASE. A photocopy of the pamphlet is shown below along with a possible letter from Charles Darwin (I have not authenticated the letter).

The owners are willing to donate the material to a worthy cause, preferably a museum if it's valuable. Does anyone know of a worthy home?

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How many protein-coding genes in the human genome?

The three main human databases (GENCODE/Ensembl, RefSeq, UniProtKB) contain a total of 22,210 protein-coding genes but only 19,446 of these genes are found in all three databases. That leaves 2764 potential genes that may or may not be real. A recent publication suggests that most of them are not real genes (Abascal et al., 2018). The issue is the same problem that I discussed in recent posts [Disappearing genes: a paper is refuted before it is even published] [Nature falls (again) for gene hype].

Nature falls (again) for gene hype

Nature is arguably the most prestigious science journal. Articles published in Nature are widely perceived to be correct, unbiased, and factual. This perception is certainly true of articles that appear in the News section of the journal since these article are presumably written by expert science writers who have evaluated the new study and decided that it's worth reporting.

Sandwalk readers know that this perception is false (fake news). It turns out that science writers who publish in Nature are not very much better than science writers in general and that's not good.

I recently published a post about an extraordinary claim concerning the number of human genes [Disappearing genes: a paper is refuted before it is even published ]. It concerns a paper posted on an archive site claiming to have found 4,998 new genes of which 1,178 are new protein-coding genes (Pertea et. al., 2018). About five weeks later another paper was posted that effectively refuted the claim of new protein-coding genes (Jungreis et al., 2018). In between publication of those two papers, a freelance science writer, Cassandra Willyard, wrote an article for Nature News that covered the original claim of 4,998 new genes [New human gene tally reignites debate].

Let's see how she handled the controversy.

Disappearing genes: a paper is refuted before it is even published

Several readers alerted me to a paper that was posted on bioRxiv a few weeks ago (May 28, 2018). The paper claimed that the human genome contains 43,162 genes consisting of 21,306 protein-coding genes and 21,856 noncoding genes. The authors reported that they had discovered 3,819 new noncoding genes and 1,178 new protein-coding genes. In addition, they claim to have discovered 97,511 new splice variants raising the total number of splice variants to 12.5 per protein-coding gene although they seem to suggest that almost one-third of these splice variants are non-functional splicing errors. The most striking result, according to the authors, is that 95% of all transcripts are just transcriptional noise.

Here's the paper ...

Press release from the Francis Crick Institute misrepresents junk DNA

Press releases have become a serious problem. I'm frequently upset whenever I read a press release covering a field I'm familiar with. They rarely do a good job of explaining what's actually in the paper and putting it into the proper context. The people who write press releases are more concerned with sensationalizing the work than they are with teaching the general public about how science works. They often do this with the blessing and participation of the scientists who did the work.

Let me illustrate the problem using a recent examples from the Francis Crick Institute in London, UK [Non-coding DNA changes the genitals you're born with]. The press release covers a recent Science paper from the Lovell-Badge lab ....

Is lateral gene transfer (LGT) Lamarckian?

There's an interesting discussion going on about lateral gene transfer (LGT) in eukaryotes. LGT is the process by which DNA from one species invades the genome of another species. It was apparently very common among primitive bacteria several billion years ago and it's still quite common in modern bacteria.

There are many reports of LGT in eukaryotes but some of them seem to be due to contamination from bacteria rather than true LGT. Many scientists are skeptical of these reports; notably Bill Martin (Heinrich Heine Universität, Düsseldorf, Germany) who suggests that almost all of them are artifacts and lateral gene transfer in eukaryotes is extremely rare [see Lateral gene transfer in eukaryotes - where's the evidence?].

Fixing carbon by reversing the citric acid cycle

The citric acid cycle¹ is usually taught as depicted in the diagram on the right.² A four-carbon compound called oxaloaceate is joined to a two-carbon compound called acetyl-CoA to produce a six-carbon tricarboxylic acid called citrate. In subsequent reactions, two carbons are released in the form of carbon dioxide to regenerate the original oxaloacetate. The cycle then repeats. The reactions produce one ATP equivalent (ATP or GTP), three NADH molecules, and one QH₂ molecule.

The GTP/ATP molecule and the reduced coenzymes (NADH and QH₂) are used up in a variety of other reactions. In the case of NADH and QH₂, one of the many pathways to oxidation is the membrane-associated electron transport system that creates a proton gradient across a membrane. The electron transport complexes are buried in membranes—plasma and internal membranes in bacteria and the inner mitochondrial membrane in eukaryotes. Students are often taught that this is the only fate of NADH and QH₂ but that's not true.

One of the other common misconceptions is that the citric acid cycle runs exclusively in one direction; namely, the direction shown in the diagram. That's also not true. The reactions of the citric acid cycle are near-equilibrium reactions like most reactions in the cell. What this means is that the concentrations of the reactants and products are close to the equilibrium values so that a slight increase in one of them will lead to a rapid equilibration. The reactions can run in either direction.³

Philosophers talking about genes

It's important to define what you mean when you use the word "gene." I use the molecular definition since most of what I write refers to DNA sequences. There's no perfect definition but, for most purposes, a good working definition is: A gene is a DNA sequence that is transcribed to produce a functional product. [What Is a Gene?].

There are two types of genes: protein-coding genes and those that specify a functional noncoding RNA (i.e ribosomal RNA, lincRNA). The gene is the part of the DNA that's transcribed so it includes introns. Transcription is controlled by regulatory sequences such as promoters, operators, and enhancers but these are not part of the gene.

In addition to genes, there are many other functional parts of the genome. In the case of eukaryotic genomes, these include centromeres, telomeres, origins of replication, SARs, and some other bits. None of this is new ... these functions have been known for decades and the working definition I use has been common among knowledgeable experts for half-a-century. Scientists know what they are talking about when they say that the human genome contains about 20,000 protein-coding genes and at least 5,000 genes for non-coding RNAs. They are comfortable with the idea that our genome has lots of other functional regions that lie outside of the genes.

Non-experts may not be familiar with the topic and they may have many misconceptions about genes and DNA sequences but we don't base our science on the views of non-experts.

Because of my interest in this topic, I was intrigued by the title of a new book, The Gene: from Genetics to Postgenomics. I ordered it a soon as I heard about it and I've just finished reading it. The version I read has been translated from German by Adam Bostanci.

Required reading for the junk DNA debate

This is a list of scientific papers on junk DNA that you need to read (and understand) in order to participate in the junk DNA debate. It's not a comprehensive list because it's mostly papers that defend junk DNA and refute arguments for massive amounts of function. The only exception is the paper by Mattick and Dinger (2013).¹ It's the only anti-junk paper that attempts to deal with the main evidence for junk DNA. If you know of any other papers that make a good case against junk DNA then I'd be happy to include them in the list.

If you come across a publication that argues against junk DNA, then you should immediately check the reference list. If you do not see some of these references in the list, then don't bother reading the paper because you know the author is not knowledgeable about the subject.

Brenner, S. (1998) Refuge of spandrels. Current Biology, 8:R669-R669. [PDF]

Brunet, T.D., and Doolittle, W.F. (2014) Getting “function” right. Proceedings of the National Academy of Sciences, 111:E3365-E3365. [doi: 10.1073/pnas.1409762111]

Casane, D., Fumey, J., et Laurenti, P. (2015) L’apophénie d’ENCODE ou Pangloss examine le génome humain. Med. Sci. (Paris) 31: 680-686. [doi: 10.1051/medsci/20153106023] [The apophenia of ENCODE or Pangloss looks at the human genome]

Cavalier-Smith, T. (1978) Nuclear volume control by nucleoskeletal DNA, selection for cell volume and cell growth rate, and the solution of the DNA C-value paradox. Journal of Cell Science, 34(1), 247-278. [doi: PDF]

Doolittle, W.F. (2013) Is junk DNA bunk? A critique of ENCODE. Proc. Natl. Acad. Sci. (USA) published online March 11, 2013. [PubMed] [doi: 10.1073/pnas.1221376110]

Doolittle, W.F., Brunet, T.D., Linquist, S., and Gregory, T.R. (2014) Distinguishing between “function” and “effect” in genome biology. Genome biology and evolution 6, 1234-1237. [doi: 10.1093/gbe/evu098]

Doolittle, W.F., and Brunet, T.D. (2017) On causal roles and selected effects: our genome is mostly junk. BMC biology, 15:116. [doi: 10.1186/s12915-017-0460-9]

Eddy, S.R. (2012) The C-value paradox, junk DNA and ENCODE. Current Biology, 22:R898. [doi: 10.1016/j.cub.2012.10.002]

Eddy, S.R. (2013) The ENCODE project: missteps overshadowing a success. Current Biology, 23:R259-R261. [10.1016/j.cub.2013.03.023]

Graur, D. (2017) Rubbish DNA: The functionless fraction of the human genome Evolution of the Human Genome I (pp. 19-60): Springer. [doi: 10.1007/978-4-431-56603-8_2 (book)] [PDF]

Graur, D. (2017) An upper limit on the functional fraction of the human genome. Genome Biology and Evolution, 9:1880-1885. [doi: 10.1093/gbe/evx121]

Graur, D., Zheng, Y., Price, N., Azevedo, R. B., Zufall, R. A., and Elhaik, E. (2013) On the immortality of television sets: "function" in the human genome according to the evolution-free gospel of ENCODE. Genome Biology and Evolution published online: February 20, 2013 [doi: 10.1093/gbe/evt028

Graur, D., Zheng, Y., and Azevedo, R.B. (2015) An evolutionary classification of genomic function. Genome Biology and Evolution, 7:642-645. [doi: 10.1093/gbe/evv021]

Gregory, T. R. (2005) Synergy between sequence and size in large-scale genomics. Nature Reviews Genetics, 6:699-708. [doi: 10.1038/nrg1674]

Haerty, W., and Ponting, C.P. (2014) No Gene in the Genome Makes Sense Except in the Light of Evolution. Annual review of genomics and human genetics, 15:71-92. [doi:10.1146/annurev-genom-090413-025621]

Hurst, L.D. (2013) Open questions: A logic (or lack thereof) of genome organization. BMC biology, 11:58. [doi:10.1186/1741-7007-11-58]

Kellis, M., Wold, B., Snyder, M.P., Bernstein, B.E., Kundaje, A., Marinov, G.K., Ward, L.D., Birney, E., Crawford, G. E., and Dekker, J. (2014) Defining functional DNA elements in the human genome. Proc. Natl. Acad. Sci. (USA) 111:6131-6138. [doi: 10.1073/pnas.1318948111]

Mattick, J. S., and Dinger, M. E. (2013) The extent of functionality in the human genome. The HUGO Journal, 7:2. [doi: 10.1186/1877-6566-7-2]

Five Things You Should Know if You Want to Participate in the Junk DNA DebateMorange, M. (2014) Genome as a Multipurpose Structure Built by Evolution. Perspectives in biology and medicine, 57:162-171. [doi: 10.1353/pbm.2014.000]

Niu, D. K., and Jiang, L. (2012) Can ENCODE tell us how much junk DNA we carry in our genome?. Biochemical and biophysical research communications 430:1340-1343. [doi: 10.1016/j.bbrc.2012.12.074]

Ohno, S. (1972) An argument for the genetic simplicity of man and other mammals. Journal of Human Evolution, 1:651-662. [doi: 10.1016/0047-2484(72)90011-5]

Ohno, S. (1972) So much "junk" in our genome. In H. H. Smith (Ed.), Evolution of genetic systems (Vol. 23, pp. 366-370): Brookhaven symposia in biology.

Palazzo, A.F., and Gregory, T.R. (2014) The Case for Junk DNA. PLoS Genetics, 10:e1004351. [doi: 10.1371/journal.pgen.1004351]

Rands, C. M., Meader, S., Ponting, C. P., and Lunter, G. (2014) 8.2% of the Human Genome Is Constrained: Variation in Rates of Turnover across Functional Element Classes in the Human Lineage. PLOS Genetics, 10:e1004525. [doi: 10.1371/journal.pgen.1004525]

Thomas Jr, C.A. (1971) The genetic organization of chromosomes. Annual review of genetics, 5:237-256. [doi: annurev.ge.05.120171.001321]

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1. The paper by Kellis et al. (2014) is ambiguous. It's clear that most of the ENCODE authors are still opposed to junk DNA even though the paper is mostly a retraction of their original claim that 80% of the genome is functional.

I'm going to a birthday party!

It's Bruce Alberts' 80th birthday party in San Francisco. There will be food, wine, cake, and (probably) dancing but first you go to the symposium on education.

Bruce Alberts’ 80th Birthday Gathering and Symposium
Saturday, April 14
Symposium on Science Education and Science Policy in Honor of Bruce Alberts’ 80th Birthday
(At the Metropolitan Club, 640 Sutter St., San Francisco 94102)

9a Guests arrive and register

10a Introduction by Master of Ceremonies Gregor Eichele

10:10a Session 1 How do we convey the importance of science to the public?
Moderator: Maureen Munn
Panelists: Janet Coffey, Will Colglazier, Janet English, Caroline Kiehle

11:40a Break

12p Buffet Lunch served in the Garden Room

1:30p Session 2 Innovations in Teaching and Learning in Higher Education
Moderators: Doug Kellogg and Kimberly Tanner.
Panelists: Judy Miner, Sally Pasion (one more panelist TBA)

2:30p Coffee and tea break

3p Session 3 Challenges Facing the Next Generation of Scientists
Moderators: Cynthia Fuhrmann and Bill Theurkauf.
Panelists: Marc Kirschner, Barry Selick, Nolan Sigal

4p Break

4:30p Session 4 Science Policy
Moderators: Mary Maxon and Jason Rao
Panelists: Bill Colglazier, Haile Debas, Donna Riordan, Keith Yamamoto

5:30p Elaine Bearer’s Duet for clarinet and viola: “Replication Machine”

6:15p Reception at Metropolitan Club Bar (4th Floor)

7p Buffet Dinner (Metropolitan Club Main Dining Hall — 4th Floor) Ending at 9:30p.

Sunday, April 15

10a - 2p Drop-in Brunch for all hosted at Beth Alberts’ home

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Photo: Bruce Alberts with his first three graduate students: Glenn Herrick (right), Keith Yamamoto (left), Larry Moran (middle right), Bruce Alberts (middle left).

Cafe Scientific Mississauga: The Good, Bad, & Natural

Dan Riskin: The Good, Bad, & Natural: What Mother Nature says
about morality?

Thursday, April 12, 2018
7:30 - 10:00 pm
The Franklin House
263 Queen Street S
Streetsville (Mississauga), Ontario, Canada

"People often act like “natural” is synonymous with “good.” Using heinous examples from the scientific literature, Dan Riskin will blow the hinges off that misconception. Then he’ll give some thoughts about where, if not from nature, the roots of human morality might lie.

Dan Riskin, PhD, is a television personality, scientist, author, and podcaster. He is best known as the co-host of Discovery's flagship science program, Daily Planet, and as the host of Animal Planet's show about parasites, Monsters Inside Me. To make science accessible and interesting to wide audiences, Dan has appeared as a guest on The Tonight Show with Jay Leno, The Late Late Show with Craig Ferguson, The Dr. Oz Show, and on several news outlets, including CP24, CTV, CNN, and CBS. Dan has published more than 20 papers in scientific journals, and his first popular book, Mother Nature is Trying to Kill You was a Canadian bestseller.

IMPORTANT:
This meetup starts 30 minutes later than our regular meeting time to give Dan time to drive to Mississauga from Scarborough.
You are welcome to come at 7 or 7:30, but don't expect the talk to begin before 8 pm. It will definitely be worth it."

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Subhash Lakhotia: The concept of 'junk DNA' becomes junk

Continuing my survey of recent papers on junk DNA, I stumbled upon a review by Subash Lakhotia that has recently been accepted in The Proceedings of the Indian National Science Academy (Lakhotia, 2018). It illustrates the extent of the publicity campaign mounted by ENCODE and opponents of junk DNA. In the title of this post, I paraphrased a sentence from the abstract that summarizes the point of the paper; namely, that the 'recent' discovery of noncoding RNAs refutes the concept of junk DNA.

Lakhotia claims to have written a review of the history of junk DNA but, in fact, his review perpetuates a false history. He repeats a version of history made popular by John Mattick. It goes like this. Old-fashioned scientists were seduced by Crick's central dogma into thinking that the only important part of the genome was the part encoding proteins. They ignored genes for noncoding RNAs because they didn't fit into their 'dogma.' They assumed that most of the noncoding part of the genome was junk. However, recent new discoveries of huge numbers of noncoding RNAs reveal that those scientists were very stupid. We now know that the genome is chock full of noncoding RNA genes and the concept of junk DNA has been refuted.

Peter Larsen: "There is no such thing as 'junk DNA'"

The March 2018 issue of Chromosome Research is a Special Issue on Transposable Elements and Genome Function. I found it as I was doing my routine search for papers on junk DNA in order to see whether scientists are finally beginning to understand the issue. Peter Larsen (guest editor) wrote the introduction to the special issue. He says ...

There is no such thing as “junk DNA.” Indeed, a suite of discoveries made over the past few decades have put to rest this misnomer and have identified many important roles that so-called junk DNA provides to both genome structure and function (this special issue; Biémont and Vieira 2006; Jeck et al. 2013; Elbarbary et al. 2016; Akera et al. 2017; Chen and Yang 2017; Chuong et al. 2017). Nevertheless, given the historical focus on coding regions of the genome, our understanding of the biological function of non-coding regions (e.g., repetitive DNA, transposable elements) remains somewhat limited, and therefore, all those enigmatic and poorly studied regions of the genome that were once identified as junk are instead best viewed as genomic “dark matter.”

What's In Your Genome? - The Pie Chart

Here's my latest compilation of the composition of the human genome. It's depicted in the form of a pie chart.¹ [UPDATED: March 29, 2018]

What is "dark DNA"?

Some DNA sequencing technologies aren't very good at sequencing and assembling DNA that's rich in GC base pairs. What this means is that some sequenced genomes could be missing stretches of GC-rich DNA if they rely exclusively on those techniques. This difficult-to-sequence DNA was called "dark DNA" in a paper published last summer (July 2017).

The paper looked at some missing genes in the genome of the sand rat Psammomys obesus. The authors initially used a standard shotgun strategy in order to sequence the sand rat genome. They combined millions of short reads (&lt200 bp) to assemble a complete genome. A large block of genes seemed to be missing—genes that were conserved and present in the genomes of related species (Hargraves et al., 2017). They knew the genes were present because they could detect the mRNAs corresponding to those genes.

Making Sense of Genes by Kostas Kampourakis

Kostas Kampourakis is a specialist in science education at the University of Geneva, Geneva (Switzerland). Most of his book is an argument against genetic determinism in the style of Richard Lewontin. You should read this book if you are interested in that argument. The best way to describe the main thesis is to quote from the last chapter.

Here is the take-home message of this book: Genes were initially conceived as immaterial factors with heuristic values for research, but along the way they acquired a parallel identity as DNA segments. The two identities never converged completely, and therefore the best we can do so far is to think of genes as DNA segments that encode functional products. There are neither 'genes for' characters nor 'genes for' diseases. Genes do nothing on their own, but are important resources for our self-regulated organism. If we insist in asking what genes do, we can accept that they are implicated in the development of characters and disease, and that they account for variation in characters in particular populations. Beyond that, we should remember that genes are part of an interactive genome that we have just begun to understand, the study of which has various limitations. Genes are not our essences, they do not determine who we are, and they are not the explanation of who we are and what we do. Therefore we are not the prisoners of any genetic fate. This is what the present book has aimed to explain.

Is evolutionary psychology a deeply flawed enterprise?

We were discussing the field of evolutionary psychology at our local cafe scientific meeting last week. The discussion was prompted by watching a video of Steven Pinker in conversation with Stephen Fry. I pointed out that the field of evolutionary psychology is a mess and many scientists and philosophers think it is fundamentally flawed. The purpose of this post is to provide links to back up my claim.

Can the Dunning-Kruger effect be reversed?

The Dunning-Kruger Effect was first proposed in a classic 1999 paper (Kruger and Dunning, 1999).¹ People suffering from this effect show one of two characteristics. If they are not knowledgeable about a subject they tend to overestimate their ability. If they are experts in a subject they tend to underestimate their ability (see figure).

The phenomenon is more significant in people who overestimate their ability because it includes a large number of people who are making decisions on subjects that they know little about. Because of the Dunning-Kruger effect, they are confident that their decisions are based on facts and evidence. That's bad enough, but there's another aspect to this problem—why do these people seem to be incapable of recognizing that they are suffering from the Dunning-Kruger effect? Here's how Kruger and Dunning explain this ...

Junk DNA and selfish DNA

Selfish DNA is a term that became popular with the publication of a series of papers in Nature in 1980. The authors were referring to viruses and transposons that insert themselves into a genome where they exist solely for the purposes of propagating themselves. These selfish DNA sequences are often thought, incorrectly, to be the same as the Selfish Genes of Richard Dawkins¹ [Selfish genes and transposons]. In fact, "selfish genes" refers to the idea that some DNAs enhance fitness and the frequency of these genes will increase in a population through their effect on the vehicle that carries them. It's an adaptationist view of evolution. The selfish DNA of transposons and viruses is quite different. These sequences only propagate themselves—the fitness of the organism is largely irrelevant. These elements do not contribute directly to the adaptive evolution of the species.

Transposons and integrated viruses are subjected to mutation just like the rest of the genome. Deleterious mutations cannot be purged by natural selection because inactivating a transposon has no effect on the fitness of the organism.² As a result, large genomes are littered with defective transposons and bits and pieces of dead transposons. This is not selfish DNA by any definition. It is junk DNA [What's in Your Genome?].

Human genome books

Theme
Genomes
& Junk DNA

I'm trying to read all the recent books on the human genome and anything related. There are a lot of them. Here's a list with some brief comments. You should buy some of these books. There are others you should not buy under any circumstances.

Test your irony meter

The irony meter was a running joke on the newsgroup talk.origins back in the last century. Our irony meters were supposed to protect us from the craziness of creationists but as soon as we built a really good irony meter a new bit of creationist crazy came along and fried it. Apparently Jesus and Mo have the same problem.

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Scientists fight back against fake news and pseudoscience

You probably know that climate change is real and humans are a major cause of global warming. You probably know that life has evolved and the Biblical story of creation is false. Scientists have been actively promoting these ideas for decades and they've been relatively successful in most countries. What you may not know is that these are just two of the many controversial claims that scientists are fighting. You may even have been tricked into believing some of the other pseudoscientific claims that are out there.

Dirty bacteria

Did you know that the dirt in your local park is full of bacteria? Each scoop of soil contains millions of bacteria. And it's not just in your local park, soil bacteria are everywhere. This is part of the reason why the total mass of bacteria on the planet outweighs all of the eukayotes combined, including elephants and whales.

There are hundreds of different species of bacteria in your local dirt. They are as different from each other as moose and mushrooms.

Did you ever wonder whether the bacteria in Australian soil are similar to the bacteria in Austrian soil? Delgado-Baquerizo and his colleagues did, so they tested soils from all over the world. The results are published in a recent issue of Science (Delgado-Baquerizo et al., 2018).

The answer is yes ... and no. They looked at 237 locations on all continents except Antarctica. Most samples had about 1000 different species—the authors call them "phylotypes" because it's hard to define what a species is in bacteria. Only a small number of species (phylotypes) were found in all locations (511 out of 25,224 = 2%) but they accounted for almost half of the total mass. Here's how the authors describe their result ...

Together, our results suggest that soil bacterial communities, like plant communities, are typically dominated by a relatively small subset of phylotypes.

Most of those 511 dominant phylotypes fall into two large and diverse clades (phyla?): Proteobacteria and Actinobacteria. The distribution is shown in Figure 1 of the paper (left). It illustrates a little-known fact about bacteria; namely, that they are a very diverse group. Scientists are only beginning to explore this diversity. Only 18% of the 511 dominant phylotypes were previously known to science!

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Image Credit: Bacillus Sp. soil bacteria from The ecology of soil-borne human diseases

Delgado-Baquerizo, M., Oliverio, A.M., Brewer, T.E., Benavent-González, A., Eldridge, D.J., Bardgett, R.D., Maestre, F.T., Singh, B.K., and Fierer, N. (2018) A global atlas of the dominant bacteria found in soil. Science, 359(6373), 320-325. doi: doi: 10.1126/science.aap9516

Happy Darwin Day 2018!

Charles Darwin, the greatest scientist who ever lived, was born on this day in 1809 [Darwin still spurs tributes, debates] [Happy Darwin Day!] [Darwin Day 2017]. Darwin is mostly famous for two things: (1) he described and documented the evidence for evolution and common descent and (2) he provided a plausible scientific explanation of evolution—the theory of natural selection. He put all this in a book, The Origin of Species by Means of Natural Selection published in 1859—a book that spurred a revolution in our understanding of the natural world.

Modern evolutionary theory has advanced well beyond Darwin's theory but he still deserves to be honored for being the first to explain evolution and promote it in a way that convinced others. Here's one passage from the introduction to Origin of Species.

Although much remains obscure, and will long remain obscure, I can entertain no doubt, after the most deliberate and dispassionate study of which I am capable, that the view which most naturalists entertain, and which I formerly entertained—namely, that each species has been independently created—is erroneous. I am fully convinced that species are not immutable; but that those belonging to what are called the same genera are lineal descendants of some other and generally extinct species, in the same manner as the acknowledged varieties of any one species are the descendants of that species. Furthermore, I am convinced that Natural Selection has been the main but not exclusive means of modification.

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One philosopher's view of random genetic drift

Random genetic drift is the process whereby some allele frequencies change in a population by chance alone. The alleles are not being fixed or eliminated by natural selection. Most of the alleles affected by drift are neutral or nearly neutral with respect to selection. Some are deleterious, in which case they may be accidentally fixed in spite of being selected against. Modern evolutionary theory incorporates random genetic drift as part of population genetics and modern textbooks contain extensive discussions of drift and the influence of population size. The scientific literature has focused recently on the Drift-Barrier Hypothesis, which emphasizes random genetic drift [Learning about modern evolutionary theory: the drift-barrier hypothesis].

Most of the alleles that become fixed in a population are fixed by random genetic drift and not by natural selection. Thus, in a very real sense, drift is the dominant mechanism of evolution. This is especially true in species with large genomes full of junk DNA (like humans) since the majority of alleles occur in junk DNA where they are, by definition, neutral.¹ All of the data documenting drift and confirming its importance was discovered by scientists. All of the hypotheses and theories of modern evolution were, and are, developed by scientists.

Nothing in biology makes sense except in the light of population genetics.

Michael Lynch
You might be wondering why I bother to state the obvious; after all, this is the 21st century and everyone who knows about evolution should know about random genetic drift. Well, as it turns out, there are some people who continue to make silly statements about evolution and I need to set the record straight.

One of those people is Massimo Pigliucci, a former scientist who's currently more interested in the philosophy of science. We've encountered him before on Sandwalk [Massimo Pigliucci tries to defend accommodationism (again): result is predictable] [Does Philosophy Generate Knowledge?] [Proponents of the Extended Evolutionary Synthesis (EES) explain their logic using the Central Dogma as an example]. I looks like Pigliucci doesn't have a firm grip on modern evolutionary theory.

His main beef isn't with evolutionary biology. He's mostly upset about the fact that science as a way of knowing is extraordinarily successful whereas philosophy isn't producing many results. He loves to attack any scientist who points out this obvious fact. He accuses them of "scientism" as though that's all it takes to make up for the lack of success of philosophy. His latest rant appears on the Blog of the American Philosophers Association: The Problem with Scientism.

I'm not going to deal with the main part of his article because it's already been covered many times. However, there was one part that caught my eye. That's the part where he lists questions that science (supposedly) can't answer. The list is interesting. Pigliucci says,

Next to last, comes an attitude that seeks to deploy science to answer questions beyond its scope. It seems to me that it is exceedingly easy to come up with questions that either science is wholly unequipped to answer, or for which it can at best provide a (welcome!) degree of relevant background knowledge. I will leave it to colleagues in other disciplines to arrive at their own list, but as far as philosophy is concerned, the following list is just a start:

• In metaphysics: what is a cause?
• In logic: is modus ponens a type of valid inference?
• In epistemology: is knowledge “justified true belief”?
• In ethics: is abortion permissible once the fetus begins to feel pain?
• In aesthetics: is there a meaningful difference between Mill’s “low” and “high” pleasures?
• In philosophy of science: what role does genetic drift play in the logical structure of evolutionary theory?
• In philosophy of mathematics: what is the ontological status of mathematical objects, such as numbers?

[my emphasis LAM]

Before getting to random genetic drift, I'll just note that my main problem with Pigliucci's argument is that there are other definitions of science that render his discussion meaningless. For example, I prefer the broad definition of science—the one that encompasses several of the Pigliucci's questions [Alan Sokal explains the scientific worldview][Territorial demarcation and the meaning of science]. The second point is that no matter how you define knowledge, philosophers haven't been very successful at adding to our knowledge base. They're good at questions (see above) but not so good at answers. Thus, it's reasonable to claim that science (broad definition) is the only proven method of acquiring knowledge. If that's scientism then I think it's a good working hypothesis.

Now back to random genetic drift. Did you notice that one of the questions that science is "wholly unequiped" to answer is the following: "what role does genetic drift play in the logical structure of evolutionary theory?" Really?

Pigliucci goes on to explain what he means ...

The scientific literature on all the above is basically non-existent, while the philosophical one is huge. None of the above questions admits of answers arising from systematic observations or experiments. While empirical notions may be relevant to some of them (e.g., the one on abortion), it is philosophical arguments that provide the suitable approach.

I hardly know what to say.

How many of you believe that the following statements are true with respect to random genetic drift and evolutionary theory?

1. The scientific literature on all the above is basically non-existent.
2. The philosophical literature is huge.
3. The question does not admit of answers arising from systematic observations or experiments.
4. It is philosophical arguments that provide the suitable approach.

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1. There are some very rare exceptions where a mutation in junk DNA may have detrimental effects.