More Recent Comments

Showing posts sorted by relevance for query domains. Sort by date Show all posts
Showing posts sorted by relevance for query domains. Sort by date Show all posts

Thursday, September 10, 2009

The Last Universal Common Ancestor

 
Jeffrey Wong is a former member of our Department1 and the author of the best theory on the origin of the genetic code [see: Amino Acids and the Racemization "Problem"]

LUCA, LECA and LBACA--Root of Life and Roots of the Biological Domains

Dr. Jeffrey Wong
Department of Biochemistry
Hong Kong University of Science and Technology

4:30 pm, September 10
Medical Sciences Building room 4171


His mother's photograph is on the wall of graduates on the first floor of our building. She graduated from medical school in 1929.

Sunday, October 19, 2014

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.


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]

Monday, July 28, 2014

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 ...

Saturday, December 27, 2008

On the Origin of Eukaryotes

 
Theme

The Three Domain Hypothesis
If all you do is read the textbooks, you would think that the origin of eukaryotic cells has been discovered. Most textbooks describe the Three Domain Hypothesis as a done deal. Eukaryotes and archaebacteria share a more recent common ancestor than either group does with the remaining groups of bacteria. Thus, eukaryotes arose from archaebacteria.

The scientific literature does not reflect this confidence. In fact, there is general agreement that the classic Three Domain Hypothesis is no longer viable as a complete explanation for the origin of eukaryotic cells. The current consensus favors a more confused picture of early life with lots of gene swapping—the so-called web of life. It is not clear that eukaryotes as a group arose from any particular prokaryotic clade. It is likely that in addition to horizontal gene transfer, there were probably one or more fusion events where the cells from two separate lineages united to form a hybrid.1

This week's issue of the Proceedings of the National Acedemy of Sciences (USA) has a paper that addresses the problem, one more time. Cox et al. (2008) ask whether there is phylogenetic support for the Three Domain Hypothesis by analyzing 53 well conserved genes. The answer is no. But is there support for one of the alternatives, the Eocyte Hypothesis? The answer is, maybe.2

The commentary by John Archibald is worth reading. Here's an excerpt.
Evolving Views on the Tree of Life

Next to life itself, the origin of complex cells is one of the most fundamental, and intractable, problems in evolutionary biology. Progress in this area relies heavily on an understanding of the relationships between present-day organisms, yet despite tremendous advances over the last half-century scientists remain firmly divided on how to best classify cellular life. Many adhere to the textbook concept of 2 basic types of cells, prokaryotes and eukaryotes, as championed by Stanier and van Niel (7). Others posit that at its deepest level life is not a dichotomy but a trichotomy comprised of cells belonging to the domains Bacteria, Archaea, and Eukarya, each monophyletic and sufficiently distinct from one another to warrant equal status (5, 8). The conceptual and practical challenges associated with establishing a genealogy-based classification scheme for microbes have been fiercely debated for decades (see ref. 9 for recent review), and the literature is rich in philosophy and rhetoric.

The genomics revolution of the 1990s brought tremendous optimism to the field of microbial systematics: if enough genomes from diverse organisms could be sequenced and compared, definitive answers to questions about evolutionary relationships within and between eubacteria, archaebacteria, and eukaryotes would surely emerge. More specifically, it should be possible to discern how eukaryotes evolved from prokaryotes (if indeed that is what happened), and perhaps even who among modern-day prokaryotic lineages is our closest ancestor. Unfortunately, with the sequences of hundreds of eubacterial, archaebacterial, and eukaryotic genomes has come the realization that the number of universally distributed genes suitable for global phylogenetic analysis is frustratingly small (10). Lateral (or horizontal) gene transfer has shown itself to be a pervasive force in the evolution of both prokaryotic and eukaryotic genomes, and even if a “core” set of genes can be identified (and there is much debate on this issue), how confident are we that the phylogenetic signal in these genes reflects the vertical history of cells? How meaningful are sequence alignment-independent, gene content-based approaches to resolving the “tree of life” (11)? To what extent is a “net of life” a more accurate and useful metaphor for describing the full spectrum of life on Earth (10, 12–14)?
The bottom line is that the earliest stages of evolution are still very much open questions. It is wrong to assume that the Three Domain Hypothesis is correct and scientists, as well as textbooks writers, should stop making this assumption.


1. Most workers make the unstated assumption that eukaryotic cells are more recent than prokaryotic cells. The idea that archaebacteria could have arisen by a fusion of an early eukaryote with an early prokaryote is just as consistent with most of the data yet this possibility is almost never discussed.

2. Cox et al. use very "sophisticated" techniques for analyzing their sequence data. Much of the controversy in this field involves disputes over which computer programs give the most accurate results. What's really going on, in my opinion, is that the data isn't good enough to justify the kinds of manipulations that are being done. The trees give you a good approximation of the true phylogeny but subjecting the data to over-analysis isn't helpful.

Archibald, J.M. (2008) The eocyte hypothesis and the origin of eukaryotic cells. Proc. Natl. Acad. Sci. (USA) 105:20049-20050. [doi:10.1073/pnas.0811118106]

Cox, C.J., Foster, P.G., Hirt, R.P., Harris, S.R., and Embley, T.M. (2008) The archaebacterial origin of eukaryotes. Proc. Natl. Acad. Sci. (USA) 105:20356-20361. [doi:10.1073/pnas.0810647105].

Friday, November 09, 2018

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.

Thursday, December 31, 2020

On the importance of controls

When doing an exeriment, it's important to keep the number of variables to a minimum and it's important to have scientific controls. There are two types of controls. A negative control covers the possibility that you will get a signal by chance; for example, if you are testing an enzyme to see whether it degrades sugar then the negative control will be a tube with no enzyme. Some of the sugar may degrade spontaneoulsy and you need to know this. A positive control is when you deliberately add something that you know will give a positive result; for example, if you are doing a test to see if your sample contains protein then you want to add an extra sample that contains a known amount of protein to make sure all your reagents are working.

Lots of controls are more complicated than the examples I gave but the principle is important. It's true that some experiments don't appear to need the appropriate controls but that may be an illusion. The controls might still be necessary in order to properly interpret the results but they're not done because they are very difficult. This is often true of genomics experiments.

Wednesday, November 22, 2006

The Three Domain Hypothesis (part 2)

Jan Sapp sets the tone by outlining the history of bacterial classification and phylogenetic analysis. We’re mostly concerned with the fourth era—the one that begins in the 1990's with the publication of the first bacterial genomes.
By the late 1990's, just when the three-domain proposal and the outlines of a “universal phylogenetic tree” were becoming well established, the microbial order based on rRNA was challenged by data from complete genome analysis of bacteria. Phylogenies based on genes other than those for rRNA often indicated different genealogies, and indeed a somewhat chaotic order. The new genomic data also indicated that archaebacteria and bacteria had many genes in common: perhaps they were not that different after all.
Sapp then goes on to discuss the attack on the Three Domain Hypothesis by Ernst Mayr in an oft-quoted PNAS paper (Mayr, 1998). Mayr’s objections have more to do with classification and taxonomy than with any real dispute over the validity of the molecular data. It’s about the fact that Mayr doesn’t like cladistics. He doesn’t want molecular phylogenies to trump visible phenotypes and “common sense” (Mayr’s, of course). Mayr argues that archaebacteria and bacteria both look like bacteria so they should be lumped together in a single prokaryotic empire.

I’m not interested in that debate. If the gene trees say that archaebacteria form a separate domain then that’s good enough for me no matter how much they resemble other prokaryotes. Woese (1998) has published an adequate reply to Mayr.

The real arguments are based on conflicting gene trees and the increasingly obvious similarity between bacteria and archaebacteria at the molecular level. How do we resolve the conflicts between the ribosomal RNA trees and examples of equally well-supported trees from proteins? The first thing that comes to mind is that some of the gene phylogenies are just wrong. They are artifacts of some sort and don’t really represent the history of the genes. Most of the debate on this topic concerns the validity of the SSU trees since they are based on nucleotide sequences. It’s well-known that ribosomal RNA trees are prone to long branch attraction artifacts to a greater extend than trees based on amino acid sequences. It’s also well-known that there are some famous mistakes in rRNA trees.

For the time being, let’s assume that all genes trees are accurate representations of the gene history, bearing in mind that the opponents of the Three Domain Hypothesis are not prepared to concede that point.

Conflicting gene trees then have to be artifacts of a different sort. Some of them will accurately represent the evolution of the species while others will not. The ones that don’t follow the phylogeny of the species will deviate because the genes have a different history. Either they have been transferred singly from one species to another or they have been transferred en masse by some sort of fusion event. Sapp discusses both these possibilities.

Lateral gene transfer (LTG)—also called horizontal gene transfer (HGT)—is the latest fad in microbial evolution. You can explain away all the conflicting gene phylogenies by invoking interspecies transfer. But here’s the problem: which genes were transferred and which ones represent the “true” species phylogeny? Several papers in the book address this problem and we’ll cover them in separate postings.

Keep in mind that LGT can get you out of a messy situation but there’s a price to pay. If you envisage a time when cells were frequently swapping lots of genes to form a “net” of life, then that, in and of itself, is enough to refute the standard version of the Three Domain Hypothesis. What you’re left with is a hypothesis about the phylogeny of “some” genes and a different phylogeny for others. This gets us into playground fights about “my gene is better than your gene.” Supporters of the Three Domain Hypothesis are willing to go there in order to save the hypothesis. Do their arguments hold up?

The other way of explaining the conflict is to invoke whole genome fusions followed by selective loss of half the genes. There are several models to explain the origin of eukaryotic cells by fusion of a primitive archaebacterium with a primitive bacterium. Such an event would account for the data, which shows that most eukaryotic genes are more closely related to bacteria but some are closer to archaebacteria. There are other interesting models, for example one model postulates fusion of a primitive eukaryotic cell with a primitive bacterial cell to form the first archaebacterium! This also accounts for the data but it pretty much wipes out one of the three domains!

Most people take these fusion models seriously. If one of the fusion models is correct, then the original Three Domain Hypothesis is refuted. (One of the complications is the transfer of genes from mitochondria to the eukaryotic nucleus. We’re not talking about those genes. Those ones are relatively easy to recognize.)

Jan Sapp closes his introduction with a summary of the problems that will be addressed in the rest of the book.
... with the development of genomics, the hitherto unappreciated ubiquity of LGT was postulated to explain many gene histories other than those for rRNA. The species concept was again considered to be inapplicable to bacteria, not because of the absence of genetic recombination, as long thought, but because there seemed to be so little barrier to it. Doubts about the inability to construct bacterial genealogies arose anew because of the scrambling of the genetic record from LGT. While debates continue over which (if any) provide the most reliable phylogenetic guide, so too do debates over the origin of the eukaryotic cell nucleus and over the inheritance of acquired bacterial genomes.


Microbobial Phylogeny and Evolution: Concepts and Controversies Jan Sapp, ed., Oxford University Press, Oxford UK (2005)
Jan Sapp The Bacterium’s Place in Nature
Norman Pace The Large-Scale Structure of the Tree of Life.
Woflgang Ludwig and Karl-Heinz Schleifer The Molecular Phylogeny of Bacteria Based on Conserved Genes.
Carl Woese Evolving Biological Organization.
W. Ford Doolittle If the Tree of Life Fell, Would it Make a Sound?.
William Martin Woe Is the Tree of Life.
Radhey Gupta Molecular Sequences and the Early History of Life.
C. G. Kurland Paradigm Lost.


Mayr, E. (1998) Two Empires or Three? Proc. Natl. Acad. Sci. USA 95:9720-0823.

Woese, C. R. (1998) Default taxonomy: Ernst Mayr’s view of the microbial world. Proc. Natl. Adad. Sci. USA 95:11043-11046.


Tuesday, December 06, 2016

How many proteins in the human proteome?

Humans have about 25,000 genes. About 20,000 of these genes are protein-coding genes.1 That means, of course, that humans make at least 20,000 proteins. Not all of them are different since the number of protein-coding genes includes many duplicated genes and gene families. We would like to know how many different proteins there are in the human proteome.

The latest issue of Science contains an insert with a chart of the human proteome produced by The Human Protein Atlas. Publication was timed to correspond with release of a new version of the Cell Atlas at the American Society of Cell Biology meeting in San Francisco. The Cell Atlas maps the location of about 12,000 proteins in various tissues and organs. Mapping is done primarily by looking at whether or not a gene is transcribed in a given tissue.

A total of 7367 genes (60%) are expressed in all tissues. These "housekeeping" genes correspond to the major metabolic pathways and the gene expression pathway (e.g. RNA polymerase subunits, ribosomal proteins, DNA replication proteins). Most of the remaining genes are tissue-specific or developmentally specific.

Friday, October 10, 2014

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.)

Thursday, November 26, 2015

Quotations

I'm creating a post where I can store quotations so I can link to them from other posts. Enjoy.
The great fear of many leading creationists and the misunderstanding of many creationist students is that accepting MN [methodological naturalism] rules for doing science will necesarily lead to a supernaturalless/Godless worldview.
Brian Alters (2005) p. 77

Persons in this faction [of theists] basically accept evolutionary theory with the proviso that the God of the Bible, not chance, decided the human outcome by directly guiding the process. Such theists are most commonly referred to as theistic evolutionists.
Brian Alters (2005) p. 62

Science reveals where religion conceals. Where religion purports to explain, it actually resorts to tautology. To assert that "God did it" is no more than an admission of ignorance dressed deceitfully as an explanation...
Peter Atkins

The defective design of organisms could be attributed to the gods of the ancient Greeks, Romans, and Egyptians, who fought with one another, made blunders, and were clumsy in their endeavors. But, in my view, it is not compatible with special action by the omniscient and omnipotent God of Judaism, Christianlity, and Islam.
Francisco J. Ayala (2004) p. 71

In conclusion, then, macroevolutionary processes are underlain by microevolutionary phenomena and are compatible with microevolutionary theories, but macroevolutionary studies require the formulation of autonomous hypotheses and models (which must be tested using macroevolutionary evidence). In this (epistemologically) very important sense, macroevolution is decoupled from microevolution: macroevolution is an autonomous field of evolutionary study.
Francisco J. Ayala (1983) p. 131

Science is not committed to the nonexistence of God, as it would be if it were based on metaphysical naturalism. Science is committed to naturalistic explanations. Science does not count any explanation that appeals to God or to supernatural phenomena as a scientific explanation (thus it is committed to methodological naturalism).
Lynn Rudder Baker (2000)

I once made the remark that two things disappeared in 1990: one was communism, the other was biochemistry and that only one of them should be allowed to come back.
Sydney Brenner (2000)

There will be no difficulty in computers being adapted to biology. There will be luddites. But they will be buried.
Sydney Brenner

One of the most frightening things in the Western world, and in this country in particular, is the number of people who believe in things that are scientifically false. If someone tells me that the earth is less than 10,000 years old, in my opinion he should see a psychiatrist.
Francis Crick

The Astonishing Hypothesis is that "You," your joys and your sorrows, your memories and your ambitions, your sense of personal identity and free will, are in fact no more than the behavior of a vast assembly of nerve cell and their associated molecules.
Francis Crick (1994)

My own view is that conclusions about the evolution of human behavior should be based on research at least as rigorous as that used in studying nonhuman animals. And if you read the animal behavior journals, you'll see that this requirement sets the bar pretty high, so that many assertions about evolutionary psychology sink without a trace.
Jerry Coyne (2009)

Although I am fully convinced of the truth of the views given in this volume, I by no means expect to convince experienced naturalists whose minds are stocked with a multitude of facts all viewed, during a long course of years, from a point of view directly opposite to mine. It is so easy to hide our ignorance under such expressions as "plan of creation," "unity of design," etc., and to think that we give an explanation when we only restate a fact. Any one whose disposition leads him to attach more weight to unexplained difficulties than to the explanation of a certain number of facts will certainly reject the theory.
Charles Darwin (1859)

The old argument of design in nature, as given by Paley, which formerly
seemed to me to be so conclusive, fails, now that the law of natural selection has been discovered. We can no longer argue that, for instance, the beautiful hinge of a bivalve shell must have been made by an intelligent being, like the hinge of a door by man. There seems to be no more design in the variability of organic beings and in the action of natural selection, than in the course which the wind blows.

Charles Darwin (c1880)

An atheist before Darwin could have said, following Hume: 'I have no explanation for complex biological design. All I know is that God isn't a good explanation, so we must wait and hope that somebody comes up with a better one.' I can't help feeling that such a position, though logically sound, would have left one feeling pretty unsatisfied, and that although atheism might have been logically tenable before Darwin, Darwin made it possible to be an intellectually fulfilled atheist.
Richard Dawkins

Theologians, if they want to remain honest, should make a choice. You can claim your own magisterium, separate from science's but still deserving of respect. But in that case you have to renounce miracles. Or, you can keep your Lourdes and your miracles ... But then you must kiss goodbye to separate magisteria and your high-minded aspiration to converge on science. The desire to have it both ways is not surprising in a good propagandist. What is surprising is the readiness of liberal agnostics to go along with it; and their readiness to write off, as simplistic, insensitive extremists, those of us with the temerity to blow the whistle.
Richard Dawkins (2003) p.150

It is absolutely safe to say that if you meet someone who claims not to believe in evolution, that person is ignorant, stupid or insane (or wicked, but I'd rather not consider that).
Richard Dawkins (1989)

... those evolutionists who see no conflict between evolution and their religious beliefs have been careful not to look as closely as we have been looking, or else hold a religious view that gives God what we might call a merely ceremonial role to play.
Daniel C. Dennett (1995) p.310

Operational science takes no position about the existence or non-existence of the supernatural; it only requires that this factor is not to be invoked in scientific explanations. Calling down special-purpose miracles as explanations constitutes a form of intellectual "cheating."
Richard E. Dickerson (1992) p.119

Seen in the light of evolution, biology is, perhaps, intellectually the most satisfying and inspiring science. Without that light it becomes a pile of sundry facts—some of them interesting or curious but making no meaningful picture as a whole.
Theodosius Dobbzhansky (Dobzhansky 1973)

It is wrong to hold creation and evolution as mutually exclusive alternatives. I am a creationist and an evolutionist. Evolution is God's, or Nature's method of creation. Creation is not an event that happened in 4004 BC; it is a process that began some 10 billion years ago and is still under way.
Theodosius Dobbzhansky (Dobzhansky 1973)

Under the conditions described [for Hardy-Weinberg equilibrium], there is a genetic inertia in mendelian populations. Unless mutation, selection, differential migration, certain changes in the mating pattern, or a drop in population size disturbs the equilibrium, there is no change in the genetic structure of the population. To a very large degree, overcoming this inertia (especially changing of the gene frequency) is what is described as "evolution."
Paul R. Ehrlich and Richard W. Holm (1963) p.95

Speciation is critical to conserving the results of both natural selection and genetic drift. Speciation is obviously central to the fate of genetic variation, and a major shaper of patterns of evolutionary change through evolutionary time. It is as if Darwinians—neo- and ulra- most certainly included—care only for the process generating change, and not about its ultimate fate in geological time.
Niles Eldredge (1995) p.106

Macroevolution is more than repeated rounds of microevolution.
Douglas H. Erwin (2000)

Just as mutation and drift introduce a strong random component into the process of adaptation, mass extinctions introduce chance into the process of diversification. This is because mass extinctions are a sampling process analogous to genetic drift. Instead of sampling allele frequenceis, mass extinctions samples species and lineages. ... The punchline? Chance plays a large role in the processes responsible for adaptation and diversity.
Freeman and Herron (1998) p.520

It is naïve to think that if a species' environment changes the species must adapt or else become extinct.... Just as a changed environment need not set in motion selection for new adaptations, new adaptations may evolve in an unchanging environment if new mutations arise that are superior to any pre-existing variations.
Douglas Futuyma

There is no justification for teaching creationism in the science classroom. But if it were taught, would it be subjected to the same critical analysis as the creationists insist should be brought to bear on evolution?
Douglas J. Futuyma (1982) p.217

I have championed contingency, and will continue to do so, because its large realm and legitimate claims have been so poorly attended by evolutionary scientists who cannot discern the beat of this different drummer while their brains and ears remain tuned to only the sounds of general theory.
Stephen Jay Gould (2002) p. 1339

The essence of Darwinism lies in its claim that natural selection creates the fit. Variation is ubiquitous and random in direction. It supplies raw material only. Natural selection directs the course of evolutionary change.
Stephen Jay Gould (1980)

Progress is a noxious, culturally embedded, untestable, nonoperational, intractable idea that must be replaced if we wish to understand the patterns of history.
Stephen Jay Gould (1988)

The shift of gene frequencies in local populations is an adequate model for all evolutionary processes—or so the current orthodoxy states.
Stephen Jay Gould (1980) p. 187

Rudyard Kipling asked how the leopard got its spots, the rhino its wrinkled skin. He called his answers "just-so stories." When evolutionists try to explain form and behavior, they also tell just-so stories—and the agent is natural selection. Virtuosity in invention replaces testability as the criterion for acceptance.
Stephen Jay Gould (1980)

Since 'change of gene frequencies in populations' is the 'official' definition of evolution, randomness has transgressed Darwin's border and asserted itself as an agent of evolutionary change.
Stephen Jay Gould (1983) p. 335

The first commandment for all versions of NOMA might be summarized by stating: "Thou shalt not mix the magisteria by claiming that God directly ordains important events in the history of nature by special interference knowable only through revelation and not accessible to science." In common parlance, we refer to such special interference as "miracle"—operationally defined as a unique and temporary suspension of natural law to reorder the facts of nature by divine fiat.
Stephen Jay Gould (1999) p. 84

[My diagram] accepts the Darwinian contention that microevolutionary modes and principles can build grand patterns by cumulation through geological immensity, but rejects the argument that such extrapolations can render the entire panoply of phenomena in life's history without adding explicitly macroevolutionary modes for distinctive expression of these processes at higher tiers of time ...
Stephen Jay Gould (2002) p. 21

The world is not inhabited exclusively by fools, and when a subject arouses intense interest, as this one has, something other than semantics is usually at stake.
Stephen Jay Gould (1982)

We wish to question a deeply engrained habit of thinking among students of evolution. We call it the adaptationist programme, or the Panglossian paradigm.
S.J. Gould & R.C. Lewontin (1979) p. 584

We welcome the richness that a pluralist approach, so akin to Darwin's spirit, can provide.
S.J. Gould & R.C. Lewontin (1979) p. 584

My practise as a scientist is atheistic. That is to say, when I set up an experiment I assume that no god, angel, or devil is going to interfere with its course; and this assumption has been justified by such success as I have achieved in my professional career. I should therefore be intellectually dishonest if I were not also atheistic in the affairs of the world. And I should be a coward if I did not state my theoretical views in public.
J.B.S. Haldane

Since religion ... stands or falls with the question of cosmic purpose, the Darwinian debunking of design—and with it the apparent undoing of cosmic teleology as well—strikes right at the heart of the most prized religious intuition of humans, now and always.
John F. Haught (2004) p. 230

Whatever the God implied by evolutionary theory may be like, He is not the Protestant God of waste not, want not. He is also not a loving God who cares about his productions. He is not even the awful God portrayed in the book of Job. The God of the Galapagos is careless, wasteful, indifferent, almost diabolical. He is certainly not the sort of God to whom anyone would be inclined to pray.
David I. Hull (1991) p. 486

Johnson finds the commitment of scientists to totally naturalistic explanations dogmatic and close-minded, but scientists have no choice. Once they allow reference to God or miraculous forces to explain the first origin of life or the evoluton of the human species, they have no way of limiting this sort of explanation.
David I. Hull (1991) p. 486

This evolutionary procedure —the formation of a dominant neocortex coupled with the persistence of a nervous and hormonal system partially, but not totally, under the rule of the neocortex—strongly resembles the tinkerer's procedure. It is somewhat like adding a jet engine to an old horse cart. It is not surprising ... that accidents, difficulties, and conflicts can occur.
François Jacob (1977) p.1166
Jacob, F. (1977) Evolution and Tinkering Sci. 196:1161-1166.

Natural selection has no analogy with any aspect of human behavior. However, if one wanted to play with a comparison, one would have to say that natural selection does not work as an engineer works. It works like a tinkerer—a tinkerer who does not know exactly what he is going to produce but uses whatever he finds around him whether it be pieces of string, fragments of wood, or old cardboards; in short it works like a tinkerer who uses everything at his disposal to produce some kind of workable object.
François Jacob (1977) p.1163

It is hard to realize that the living world as we know it is just one among many possibilities; that its actual structure results from the history of the earth. Yet living organisms are historical structures: literally creations of history. They represent, not a perfect product of engineering, but a patchwork of odd sets pieced together when and where opportunities arose. For the opportunism of natural selection is not simply a matter of indifference to the structure and operation of its products. It reflects the very nature of a historical process full of contingency.
François Jacob (1977) p.1166

Ecologists and microevolutionists are beginning to appreciate the importance of events over larger time scales than the decades or centuries that are their usual bounds, and a new effort is needed from both neontological and paleontological sides to get beyond a simple extrapolation of ecological phenomena into macroevolutionary time scales.
Jablonski, D. et al (1997)

Many biochemists find it easy to accept the concept that large portions of protein molecules serve mainly to bring the molecule up to suitable size and shape and have very little specific function as compared with small specialized active sites. Most of a protein molecule, according to this concept, can evolve freely by random drift
Thomas H. Jukes (1980) p.204

In conclusion, I would like to emphasize the importance of random genetic drift as a major cause of evolution. We must be liberated, so to speak, from the selective constraint posed by the neo-Darwinian (or the synthetic) theory of evolution.
Motoo Kimura (1991)

In contrast to the Darwinian theory of evolution by natural selection, the neutral theory emphasizes the great importance of random genetic drift (due to finite population size) and mutation pressure as the main causes of molecular evolution.
Motoo Kimura (1991)

According to the neutral mutation–random drift hypothesis of molecular evolution and polymorphism1,2, most mutant substitutions detected through comparative studies of homologous proteins (and the nucleotide sequences) are the results of random fixation of selectively neutral or nearly neutral mutations. This is in sharp contrast to the orthodox neo-Darwinian view that practically all mutant substitutions occurring within species in the course of evolution are caused by positive Darwinian selection.
Motoo Kimura (1977)

Calculating the rate of evolution in terms of nucleotide substitutions seems to give a value so
high that many of the mutations involved must be neutral ones

Motoo Kimura 1968

Selective elimination of definitely deleterious mutants and random fixation of selectively neutral or very slightly deleterious mutants occur far more frequently in evolution than positive Darwinian selection of definitely advantageous mutants.
Motoo Kimura and Tomoko Ohta (1974)

The main tenet of the neutral theory is that the great majority of evolutionary changes at the molecular level are caused not by Darwinian selection but by random fixation of selectively neutral (or very nearly neutral) alleles through random sampling drift under continued mutation pressure.
Motoo Kimura (1989)

There appears to be considerable latitude at the molecular level for random genetic changes that have no effect upon the fitness of the organism. Selectively neutral mutations, if they occur, become passively fixed as evolutionary changes through the action of random genetic drift.
J.L King and T.H. Jukes (1969) p.789

The idea of selectively neutral change at the molecular level has not been readily accepted by many classical evolutionists, perhaps because of the pervassiveness of Darwinian thought.
J.L King and T.H. Jukes (1969) p.788

The suggestion that macroevolution should be divorced from microevolution provides Creationists only with a debating point. It allows Creationists to say that there are some evolutonary theorists who distinguish the mechanisms studied in classical population genetics from those they take to be involved in large-scale evolutionary change ... But this is not to suppose that the distinction drawn by heterodox evolutionists is that favored by the Creationists.
Philip Kitcher (1982) p.150

Overheard at breakfast on the final day of a recent scientific meeting: "Do you believe in macroevolution?" Came the reply: "Well, it depends on how you define it.".
Roger Lewin (1980) p.884.

The central question of the Chicago conference was whether the mechanisms underlying microevolution can be extrapolated to explain the phenomena of macroevolution. At the risk of doing violence to the positions of some of the people at the meeting, the answer can be given as a clear, No.
Roger Lewin (1980) p.884.

The fact is that almost the entire theoretical apparatus of random genetic drift and directional selection can be derived from a haploid model of the genome and that the introduction of diploidy and sexual recombination makes no qualitative chane and only trivial quantitative changes in the predictions of evolution under these forces.
Richard C. Lewontin (1974) p.83

The [neoclassical] theory does not deny adaptive evolution but only that the vast quantity of molecular variation within populations and, consequently, much of the molecular evolution among species, has anything to do with that adaptive process
Richard C. Lewontin (1974) p.85

The false view of evolution as a process of global optimizing has been applied literally by engineers who, taken in by a mistaken metaphor, have attempted to find globally optimal solutions to design problems by writing programs that model evolution by natural selection.
Richard Lewontin

Evolution is a process of change in the genetic makeup of populations, with the most basic component being change in allele frequencies with time.
Wen-Hsiung Li (1997) p.35

... the independence of macroevolution is affirmed not only by species selection but also by other processes such as effect sorting among species.
Bruce S. Lieberman and Elisabeth S. Vrba (2005)

Macroevolution is given expanded meaning by punctuated equilibrium, which is a theory more about species and their reality and individuality (sensu Hull 1980) than about speciation.
Bruce S. Lieberman and Elisabeth S. Vrba (2005)

The universe doesn't seem to me to be like the kind of entity that could have a higher purpose. I literally don't know what it would mean to say that the universe has a higher purpose. But I also have to say just simply as far as my own personal experience is concerned I have not found it a depressing doctrine. I do not find myself in the least depressed by feeling that if there is a purpose it's a purpose in my friends in my people I love and myself and human beings. It's a product of human beings it's not something that's sort of you know comes out the physical universe because the universe was created.
John Maynard Smith (1998)

Molecular genetics has found that mutations frequently occur in which the new allele produces no change in the fitness of the phenotype. Kimura (1983) has called the occurrence of such mutations neutral evolution, and others have referred to it as non-Darwinian evolution. Both terms are misleading. Evolution involves the fitness of individuals and populations, not of genes. When a genotype, favored by selection, carries along as hitchhikers a few newly arisen and strictly neutral alleles, it has no influence on evolution. This may be called evolutionary 'noise' but it is not evolution. However, Kimura is correct in pointing out that much of the molecular variation of the genotype is due to neutral mutations. Having no effect on the phenotype, they are immune to selection.
Ernst Mayr (2001) p.199

... I pointed out more than a decade ago (1977) that 'the reductionist explanation, so widely adopted in recent decades— Evolution is a change in gene frequencies in populations—is not only not explanatory, but is in fact misleading. Far more revealing is the definition: 'Evolution is change in the adaptation *and* in the diversity of populations of organisms.'
Ernst Mayr (2001) p.162

Neither the discovery of numerous new facts relating to evolution nor the development of new concepts of speciation and genetic variation have required any essential revision of the picture of evolution as developed during the evolutionary synthesis. I emphatically deny the claims of various authors that these recent developments have led to an end of Darwinism, or of neo-Darwinism, or of the evolutionary synthesis.
Ernst Mayr (1988) p.191

The attack directed by Gould and Lewontin against unsupported adaptationist explanations in the literature is fully justified. But the most absurd among these claims were made several generations ago, not by modern evolutionists.
Ernst Mayr (1988) p.152

[referring to Tielhard de Chardin] ... it's author can be accused of dishonesty only on the grounds that before deceiving others he has taken great pains to deceive himself.
Peter Medawar (1961) p.1

Although not completely random, chance does affect which mutations, which mistakes, appear in which individuals. ... this inherent unpredictability is not a matter of inadequate scientific knowledge. Rather, it is a reflection that the behavior of matter itself is indeterminate, and therefore unpredictable. It is one of the reasons why we cannot predict, with any detailed certainty, the future path of evolution.
Kenneth R. Miller (1999) p. 233

... evolution is as much a fact as anything we know in science. It is a fact that we humans did not appear suddenly on this planet, de novo creations without ancestors, and it is a fact that the threads of ancestry are clear for us and for hundreds of other species and groups.
Kenneth R. Miller (1999) p. 233

No question about it. Rewind that tape, let it run again, and events might come out differently at every turn. Surely this means that mankind's appearance on this planet was not preordained, that we are here not as the products of an inevitable procession of evolutionary success, but as an afterthought, a minor detail, a happenstance in a history that might just as well have left us out. I agree.
Kenneth R. Miller (1999) p. 233

In any discussion of the question of "Intelligent Design," it is absolutely essential to determine what is meant by the term itself. If, for example, the advocates of design wish to suggest that the intricacies of nature, life, and the universe reveal a world of meaning and purpose consistent with an overarching, possibly Divine, intelligence, then their point is philosophical, not scientific. It is a philosophical point of view, incidentally, that I share, along with many scientists.
Kenneth R. Miller (2004) p. 94

The thesis I shall present in this book is that the biosphere does not contain a predictable class of objects or of events but constitutes a particular occurrence, compatible indeed with first principles, but not deducible from those principles and therefore essentially unpredictable.
Jacques Monod (1971) p.43

All religions, nearly all philosophies, and even a part of science testify to the unwearying, heroic effort of mankind desperately denying its own contingency."
Jacques Monod (1971) p.44

Another curious aspect of the theory of evolution is that everybody thinks he understands it. I mean philosophers, social scientists, and so on. While in fact very few people understand it, actually, as it stands, even as it stood when Darwin expressed it, and even less as we now may be able to understand it in biology.
Jacques Monod (1974)

... I must correct a wrong idea that has been spreading for the past three or four years. It was discovered some years ago that in some cases, the transcription of step from DNA to RNA works in the reverse direction. That is nothing surprising. ... it could be predicted that such events could occur. They do occur, indeed, but this must not be taken to mean that information from protein could possibly go back to the genome. ... I am ready to take any bet you like that this is never going to turn out to be the case.
Jacques Monod (1974) p.394

The privilege of living beings is the possession of a structure and of a mechanism which ensures two things: (i) reproduction true to type of the structure itself, and (ii) reproduction equally true to type, of any accident that occurs in the structure. Once you have that, you have evolution, because you have conservation of accidents. Accidents can then be recombined and offered to natural selection to find out if they are of any meaning or not.
Jacques Monod (1974) p.394

The aspect of evolutionary theory that is unacceptable to many enlightened people, either scientists or philosophers, or idelogists of one kind or another, is the completely contingent aspect which the existence of man, societies, and so on, must take if we accept this theory.
Jacques Monod (1974) p.394

We must conclude that the existence of any particular species is a singular event, an event that occurred only once in the whole of the universe and therefore one that is also basically and completely unpredictable, including that one species which we are, namely man.
Jacques Monod (1974) p.395

While de Vries' and Goldschmidt's views on the origin of species were extreme and unrealistic, from our current knowledge of genetics, de Vries' ideas led Morgan (1925, 1932) to propose a more resonable theory of evolution. ... In his view, selection plays a less important role than mutation, its chief role being to preserve useful mutations and eliminate unfit genotypes. That is, natural selection is regarded merely as a sieve to choose beneficial mutations. For this reason, his theory is often called mutationism, but a better terminology would be mutation-selection theory or classical theory in Dobzansky's sense, since he did not neglect natural selection.
Masatoshi Nei (1987) p.406

At the DNA level, most new genes seem to have been produced by gene duplication and subsequent nucleotide changes .... In these cases, the mutational change of DNA (duplication and nucleotide substitution) is clearly responsible for creating a new gene of character. Natural selection plays no such role. The role of natural selection is to eliminate less fit genotypes and save a beneficial one when there are many different genotypes in the same environment. Therefore, it seems clear that at the molecular level evolution occurs primarily by mutation pressure, though positive selection certainly speeds up gene substitution in populations.
Masatoshi Nei (1987) p.415

... are all individual differences in morphological and physiological characters adaptive as claimed by extreme neo-Darwinians? More than 4 billion people live on this planet, and all of them except identical twins are different with respect to morphological and physiological characters. Are all these differences adaptive? Is random genetic drift unimportant for generating morphological and physiological diversity among organisms? It seems to me that in some morphological characters a substantial part of genetic variation is nonadaptive.
Masatoshi Nei (1987) p.422

In this book, I have examined various aspects of molecular evolution and concluded that mutation is the driving force of evolution at the molecualr level. I have also extended this view to the level of phenotypic evolution and speciation, though I do not deny the importance of natural selection in evolution. I have challenged the prevailing view that a population of organisms contains virtually all sorts of variation and that the only force necessary for a particular character to evolve is natural selection. I have also emphasized the unpredictability of the evolutionary fate of organisms caused by uncontrolable external factors such as rapid climatic changes, geological catastrophes, or even asteroid impacts.
Masatoshi Nei (1987) p.431

The primary cause of evolution is the mutational change of genes. A mutant gene or DNA sequence caused by nucleotide substitution, insertions/delections, recombination, gene conversion, and so forth may spread through the population by genetic drift and/or natural selection and eventually be fixed in the species.
Masatoshi Nei and Sudhir Kumar (2000) p.4

Most new mutations are deleterious, and most mutations with very small effects are likely to be very slightly deleterious. Such mutations are selected against in large populations, but behave as if neutral in small populations.
Tomoko Ohta (1996) p.96

Mutation is a fundamental process for evolution. Under the orthodox view, mutations are raw materials on which natural selection works and organismal evolution is mainly governed by selection. With the accumulation of molecular data, the importance of random drift is being reevaluated. If the effect of a mutant is very small, random drift rather than selection determines its fate.
Tomoko Ohta (1998) p.83

Are we here because of a natural superiority (opposable thumbs, big brains and so on), or are we just plain lucky? In other words, is the evolution of life a fair game, as the survival-of-the-fittest doctrine so strongly implies?
David Raup (1991) p.xi

Is extinction through bad luck a challenge to Darwin's natural selection? No. Natural selection remains the only viable, naturalistic explanation we have for sophisticated adaptations like eyes and wings. We would not be here without natural selection. Extinction by bad luck merely adds another element to the evolutionary process, operating at the level of species, families, and classes, rather than the level of local breeding populations of single species. Thus, Darwinism is alive and well, but, I submit, it cannot have operated by itself to produce the diversity of life today.
David Raup (1991) p.192

Evolution at the molecular level appeared to have properties that would not have been predicted if it were driven by natural selection; and much of molecular evolution is now widely (if not universally) thought to be non-adaptive.
Mark Ridley (1997) p.4

A habit has grown up among some molecular biologists of using homology to mean similarity, regardless of whether the similarity is due to descent from a common ancestor. They thus talk about the "% homology" between two molecules, meaning the percentage of amino acid, or nucleotide sites that are the same in the two molecules. They are often criticized for their unorthodox usage .
M. Ridley (1997) p.208

The working biologist's reaction on learning that evolutionary theory does not fit some philosophical criterion for what a scientific theory should be like is—so much the worse for philosophy.
M. Ridley (1997) p.368

... Kimura's original radical claim, that most molecular evolution proceeds by drift, not selection, remains intact in the nearly neutral theory. It still contrasts strongly with the view that molecular evolution is powered by Darwinian natural selection.
M. Ridley (1997) p.78

Many universes can exist, with all possible combinations of physical laws and constants. In that sense, we just happen to be in the particular one that was suited for the the evolution of our form of life. When cosmologists refer to the anthropic principle, this is all they usually mean. Since we live in this universe, we can assume it possesses qualities suitable for our existence.
Eugenie C. Scott (2004)

... the thesis that evolution is primarily driven by natural selection is sometimes called Darwinism. Unfortunately, many people misapply the term to refer to the concept of descent with modification itself, which is erroneous. Natural selection is not the same as evolution.
Eugenie C. Scott (2004) p.34

Scientists sometimes colloquially refer to macroevolution as "evolution above the species level," but this term does not do justice to the complexity of topics included within the concept.
Eugenie C. Scott (2004) p.183

Micro- and macroevolution are thus different levels of analysis of the same phenomenon: evolution. Macroevolution cannot solely be reduced to microevolution because it encompasses so many other phenomena: adaptive radiation, for example, cannot be reduced only to natural selection, though natural selection helps bring it about.
Eugenie C. Scott (2004) p.183

If God is intervening into our world, he must be doing so in some measurable way. That's what we do with science. We measure.
Michael Shermer (2006)

If a sect does officially insist that its structure of belief demands that evolution be false, then no compromise is possible. An honest and competent biology teacher can only conclude that the sect's beliefs are wrong and that its religion is a false one.
George Gaylord Simpson (1964)

I do not think that evolution is supremely important because it is my speciality. On the contrary, it is my speciality because it is supremely important.
George Gaylord Simpson (1961)

The extreme view that evolution is basically or over all an orthogenetic process is evidence that some scientists' minds tend to move in straight lines, not that evolution does.
George Gaylord Simpson (1949)

Macroevolution is decoupled from microevolution, and we must envision the process governing its course as being analogous to natural selection but operating at a higher level of organization.
Steven M. Stanley (1975) p.648

The microevolutionary process that adequately describes evolution in a population is an utterly inadaquate account of the evolution of the earth's biota. It is inadequate because the evolution of the biota is more than the mutational origin and subsequent survival or extinction of genes in gene pools. Biotic evolution is also the cladogenetic origin and subsequent survival and extinction of gene pools in the biota.
George C. Williams (1992) p.31

I'm not going to be one of these scientists who keep wafling and saying "oh well, science has it's role, religion has it's role... science has it's own kind of truth and religion has it's own kind of truth... somehow, as we work more and more they will somehow come together." I don't believe that for a minute. I don't think that Darwin would have believed it.
Edward O. Wilson

The fundamantal evolutionary event is a change in the frequency of genes and chromosome configurations in a population. If a population of butterflies shifts through time from 40 percent blue individuals to 60 percent individuals, and if the color blue is hereditary, evolution of a simple kind has occurred.
Edward O. Wilson (1992) p.75

That evolution involves nonadaptive differentiation to a large extent at the subspecies level is indicated by the kinds of differences by which such groups are actually distinguished by systematicists. It is only at the subfamily and family levels that clear-cut adaptive differences become the rule. The principal evolutionary mechanisms in the origin of species must thus be an essentially nonadaptive one.
Sewell Wright (1932) p.38

(concerning more evidence for evolution) Some beating of dead horses may be ethical, where here and there they display unexpected twitches that look like life.
Emile Zuckerkandl and Linus Pauling (1965) p.101


Alters, B. (2005) Teaching Biological Evolution in Higher Education: Methodological, Religious, and Nonreligious Issues. Jones and Bartlett Publishers, Sudbury MA USA.
Ayala, F.J. (2004) "Design and Designer Darwin's Greatest Discovery" in DEBATING DESIGN: FROM DARWIN TO DNA, W.A. Dembski and M. Ruse eds. Cambridge University Press, Cambridge UK pp.55-80.
Ayala, F.J. (1983) Beyond Darwinism? The Challenge of Macroevolution to the Synthetic Theory of Evolution. reprinted in PHILOSOPHY OF BIOLOGY, M. Ruse ed. p. 118-133.
Baker, L.R. (2000) God and Science in the Public Schools. Philosophic Exchange 30: 53-69.
Brenner, S. (2000) Biochemistry strikes back. Trends in Biochemical Sciences, 25(12), 584-584. [PDF]
Crick, F. (1994) The astonishing hypothesis the scientific search for the soul. (New York: Scribner)
Coyne, J.A. (2009) Why Evolution Is True. Viking Penguin, New York
Darwin, C. (c1880) from THE AUTOBIOGRAPHY OF CHARLES DARWIN, N. Barlow ed., Harcourt Brace (1958). Quoted in EVOLUTION EXTENDED, C. Barlow ed., MIT Press, Cambridge MA (1995) p. 260
Dawkins, R. (2003) A devil's chaplain: reflections on hope, lies, science, and love. (Boston: Houghton Mifflin Co)
Dawkins, R. (1989) review of BLUEPRINTS Solving the Mystery of Evolution New York Times. April 9, 1989 [NYT April 9, 1989]
Dennett, D. (1995) Darwin's dangerous idea: evolution and the meanings of life. (New York: Simon & Schuster)
Dickerson, R.E. (1992) The Game of Science. Journal of Molecular Evolution 34: 277-279.
Dobzhansky, T. (1973) Nothing in biology makes sense except in the light of evolution. American Biology Teacher 35:125-129. [doi: 10.2307/4444260][Full Text] [Full Text] (Reprinted in EVOLUTION, M. Ridley ed., Oxford University Press, New York (1997) pp. 378-387.)
Ehrlich, P.R. and Holm, R.W. (1963) THE PROCESS OF EVOLUTION, McGraw-Hill New York
Eldredge, N. (1995) REINVENTING DARWIN: THE GREAT DEBATE AT THE HIGH TABLE OF EVOLUTIONARY THEORY, John Wiley & Sons, Inc., New York.
Erwin, D. H. (2000) Macroevolution is more than repeated rounds of microevolution. Evolution & Development, 2:78-84. [doi: 10.1046/j.1525-142x.2000.00045.x]
Freeman, S. and Herron, J.C. (1998) EVOLUTIONARY ANALYSIS, Prentice Hall. Upper Saddle River NJ USA
Futuyma, D.J. (1982) SCIENCE ON TRIAL: THE CASE FOR EVOLUTION, Sinauer Associates, Inc., Sunderland MA USA
Gould, S.J. (2002) THE STRUCTURE OF EVOLUTIONARY THEORY Harvard University Press, Cambridge, MA (USA)
Gould, S.J. (1980) "Sociobiology and the Theory of Natural Selection" in SOCIOBIOLOGY: BEYOND NATURE/NURTURE?, G.W. Barlow and J. Silverberg eds., Westview Press Inc., Boulder, Colorado pp. 257-269. Reprinted in PHILOSOPHY OF BIOLOGY, M. Ruse ed., Macmillan Publishing Co., New York, pp. 253-263.
Gould, S.J. (1988) Trends as changes in variance: a new slant on progress and directionality in evolution (Presidential Address) J. Paleont. 62: 319-329.
Gould, S.J. (1980) "Sociobiology and the Theory of Natural Selection" in SOCIOBIOLOGY: BEYOND NATURE/NURTURE?, G.W. Barlow and J. Silverberg eds., Westview Press Inc., Boulder, Colorado pp. 257-269. Reprinted in PHILOSOPHY OF BIOLOGY, M. Ruse ed., Macmillan Publishing Co., New York, pp. 253-263.
Gould, S. J. (1982) Darwinism and the expansion of evolutionary theory. Science, 216(4544), 380-387. [doi: 10.1126/science.7041256]
Gould, S.J. (1983) "Chance Riches" in HEN'S TEETH AND HORSE'S TOES, W.W. Norton & Co., New York pp. 332-342.
Gould, S.J. (1999) Rocks of ages: science and religion in the fullness of life. (New York: Ballantine Books)
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, 205(1161), 581-598. [doi: 10.1098/rspb.1979.0086]
Haldane, J.B.S. quoted in L.B. Halstead "Evolution-the Fossils Say Yes!" in SCIENCE AND CREATIONISM A. Montagu ed. Oxford University Press (1984)
Haught, J.F. (2004) "Darwin, Design, and Divine Providence" in DEBATING DESIGN: FROM DARWIN TO DNA, W.A. Dembski and M. Ruse eds. Cambridge University Press, Cambridge UK pp.229-245.
Hull, D.L. (1991) The God of the Galapogos a review of Darwin on Trial by Phillip E. Johnson. Nature 352:485-486.
Jacob, F. (1977) Evolution and tinkering. Science (New York, NY), 196(4295), 1161. [PDF]
Jablonski, D., Benton, M.J., Gastaldo, R.A., Marshall, C.R. and Sepkoski, J.J. (1997) Macroevolution in the 21st Century, PALEO21, Frankfurt [Paleonet]
Jukes, T.H. (1980) "Neutral Changes Revisited." in EVOLUTION OF PROTEIN STRUCTURE AND FUNCTION Academic Press, Inc. pp. 203-219
Kimura, M. (1977) Preponderance of synonymous changes as evidence for the neutral theory of molecular evolution. [doi: 10.1038/267275a0]
Kimura, M. (1968) Evolutionary rate at the molecular level. Nature, 217(5129), 624-626. [PDF]
Kimura, M., and Ohta, T. (1974) On some principles governing molecular evolution. Proceedings of the National Academy of Sciences, 71(7), 2848-2852. [PDF]
Kimura, M. (1991) Recent development of the neutral theory viewed from the Wrightian tradition of theoretical population genetics. Proceedings of the National Academy of Sciences, 88(14), 5969-5973. [PDF]
Kimura, M. (1989) The neutral theory of molecular evolution and the world view of the neutralists. Genome, 31(1), 24-31. [PDF]
King, J.L., and Jukes, T.H. (1969) Non-darwinian evolution. Science, 164(3881), 788-798. [PDF]
Kitcher, P. (1982) Abusing science the case against creationism. (Cambridge, Mass: MIT Press).
Lewin, R. (1980) Evolutionary Theory Under Fire (a review of the Chicago 1980 conference on macroevolution) Science 210:883-887
Lewontin, R.C. (1974) THE GENETIC BASIS OF EVOLUTIONARY CHANGE. Columbia University Press, New York quoted in EVOLUTION, M. Ridly ed. Oxford University Press (1997) pp. 79-88.
Li, W-H. (1997) MOLECULAR EVOLUTION Sinauer Associates, Inc., Sunderland MA USA
Lieberman, B.S. and Vrba, E.S. (2005) Gould on species selection. in MACROEVOLUTION: Diversity, Disparity, Contingency. E.S. Vrba and N. Eldredge eds. supplement to Paleobiology vol. 31(2) The Paleontological Society, Lawrence, Kansas, USA
Maynard Smith, J. (1998) Robert Wright interviews John Maynard Smith.
Mayr, E. (2001) WHAT EVOLUTION IS, Basic Books, New York
Mayr, E. (1988) TOWARD A NEW PHILOSOPHY OF BIOLOGY: OBSERVATIONS OF AN EVOLUTIONIST, Harvard University Press, Cambridge MA USA
Medawar, P. (1961) review of Pierre Teilhard de Chardin's "The Phenomoenon of Man" in Mind 70:99-106. Reprinted in THE STRANGE CASE OF THE SPOTTED MICE, Oxford University Press, New York (1996) p. 1.
Miller, K.R. (1999) FINDING DARWIN'S GOD: A SCIENTIST'S SEARCH FOR COMMON GROUND BETWEED GOD AND EVOLUTION. Cliff Street Books, HarperCollins, New York, NY USA
Miller, K. (2004) "The Flagellum Unspun" in DEBATING DESIGN: FROM DARWIN TO DNA, W.A. Dembski and M. Ruse eds. Cambridge University Press, Cambridge UK pp. 81-97.
Monod, J. (1971) CHANCE AND NECESSITY, A. Wainhouse (translator), Vintage Books, New York NY USA
Monod, J. (1974) "On the Molecular Theory of Evolution" reprinted in Mark Ridley (editor) Evolution (1997) p. 389
Nei, M. (1987) MOLECULAR EVOLUTIONARY GENETICS, Columbia Univesity Press, New York NY USA
Nei, M. and Kumar, S. (2000) MOLECULAR EVOLUTION AND PHYLOGENETICS, Oxford University Press, New York NY USA
Ohta, T. (1996) The neutral theory is dead. The current significance and standing of neutral and nearly neutral theories. BioEssays, 18(8), 673-677. [doi: 10.1002/bies.950180811]
Ohta, T. (1998) Evolution by nearly-neutral mutations. Genetica, 102, 83-90.
Raup, D.M. (1991) EXTINCTION: BAD GENES OR BAD LUCK? W.W. Norton & Co., New York
Ridley, Mark (1997) in EVOLUTION, M. Ridley ed. Oxford University Press, Oxford UK.
Scott, E.C. (2004) Evolution vs. creationism: an introduction. (Westport, Conn: Greenwood Press).
Simpson, G.G. (1964) from his book THIS VIEW OF LIFE: THE WORLD OF AN EVOLUTIONIST, Harcourt Brace, quoted in EVOLUTION EXTENDED, C. Barlow ed. MIT Press, Cambridge, MA USA pp.270-271.
Stanley, S.M. (1975) A theory of evolution above the species level. Proc. Natl. Acad. Sci. (USA) 72: 646-650.
Williams, G.C. (1992) NATURAL SELECTION: DOMAINS, LEVELS AND CHALLENGES. Oxford University Press, Oxford UK.
Wilson, E.O. Robert Wright interviews E.O. Wilson
Wilson, E.O. (1992) THE DIVERSITY OF LIFE W.W. Norton & Co. New York NY USA
Wright S. (1932) The roles of mutation, inbreeding, crossbreeding and selection in evolution. Proceeding of the VI International Congree of Genetics, reprinted in EVOLUTION, Mark Ridley ed. Oxford University Press Oxford UK pp.32-40.
Zuckerkandl, E., and Pauling, L. (1965) Evolutionary divergence and convergence in proteins. Evolving genes and proteins, 97, 97-166. [PDF]

Wednesday, May 30, 2012

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?


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."

Monday, April 07, 2014

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.


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

Wednesday, November 12, 2008

Two Examples of "Alternative Splicing"

THEME:
Transcription

Last week I bumped into a colleague who teaches in our third year molecular biology course. I was lamenting about the sad state of science these days and we got to talking about alternative splicing. I repeated my complaint that much of the predicted alternative splice variants are artifacts. It makes no sense that conserved genes would be producing alternative protein variants that are species specific. I am convinced that the EST databases are full of artifacts and that most predicted splice variants do not exist.

My colleague was shocked. He is firmly convinced that most human genes express a number of different protein products that are produced as the result of alternatively spliced mRNA precursors. I asked him if he had ever looked at his favorite genes to see if the predicted variants make any sense. The ones that I've looked at certainly don't. (Join in the fun: see the challenge below.)

My colleague is very knowledgeable about the genes for the major subunits of eukaryotic RNA polymerase since it was his lab that cloned the first one. I suggested that he look at the predicted alternative splice variants of the two human genes and let me know if he is still convinced that these variants make biological sense. I'm not sure he will do it so let's take a look ourselves.

Eukaryotic RNA polymerase is a complex protein machine consisting of ten different subunits. Two of the subunits, Rpb1 and Rbp2, are more commonly known as A and B. In the human genome they are encoded by the genes POLR2A and POLR2B respectively [RNA Polymerase Genes in the Human Genome].

If you click on the Entrez Gene URLs you will end up at a page that summarizes what is known about the gene. Down the right-hand side of the page there are links to several other webpages, including a link to AceView, a database of alternative splice variants. Before following this link to the POLR1A variants, let's note that on the annotated Entrez Gene website there are no alternative splice variants listed. Apparently someone has decided that the predicted variants are probably artifacts.

Go to the AceView page for AceView POLR2A. The first thing you see is a short explanation.
RefSeq annotates one representative transcript (NM included in AceView variant.a), but Homo sapiens cDNA sequences in GenBank, filtered against clone rearrangements, coaligned on the genome and clustered in a minimal non-redundant way by the manually supervised AceView program, support at least 11 spliced variants.

AceView summary
Note that this locus is complex: it appears to produce several proteins with no sequence overlap.
Expression: According to AceView, this gene is expressed at very high level, 4.8 times the average gene in this release. The sequence of this gene is defined by 537 GenBank accessions from 518 cDNA clones, some from breast (seen 40 times), marrow (29), head neck (19), brain (18), eye (18), leukopheresis (18), lung tumor (18) and 132 other tissues. We annotate structural defects or features in 13 cDNA clones.
Alternative mRNA variants and regulation: The gene contains 29 different introns (28 gt-ag, 1 gc-ag). Transcription produces 13 different mRNAs, 11 alternatively spliced variants and 2 unspliced forms. There are 7 probable alternative promotors and 5 non overlapping alternative last exons (see the diagram). The mRNAs appear to differ by truncation of the 5' end, truncation of the 3' end, overlapping exons with different boundaries, alternative splicing or retention of 4 introns. 337 bp of this gene are antisense to spliced gene pluvu, raising the possibility of regulated alternate expression.
Protein coding potential: 10 spliced and the unspliced mRNAs putatively encode good proteins, altogether 11 different isoforms (3 complete, 4 COOH complete, 4 partial), some containing domains RNA polymerase Rpb1, domain 1, RNA polymerase, alpha subunit, RNA polymerase Rpb1, domain 3, RNA polymerase Rpb1, domain 4, RNA polymerase Rpb1, domain 5, RNA polymerase Rpb1, domain 6, RNA polymerase Rpb1, domain 7, Eukaryotic RNA polymerase II heptapeptide repeat [Pfam]. The remaining 2 mRNA variants (1 spliced, 1 unspliced) appear not to encode good proteins.
Here's the figure showing the various predicted alternatively spliced transcripts and the various different proteins.


It's really difficult to imagine that any of these are biologically relevant. How could a small bit of the large RNA polymerase subunit ever be part of the RNA polymerase protein complex? It's not a surprise that the Entrez Gene annotators have ignored these predictions.

If, as I believe, most of the small ESTs on which these predictions are based are artifacts, then the overall pattern makes sense. What you see are examples of splicing errors where an intron has not been correctly removed. These extremely rare splicing errors are copied into cDNA during construction of EST libraries and specifically selected by screening out all the correctly spliced mRNAs. (That's how you make most EST libraries.)

Here's what AceView says about the gene for the other large subbunit [AceView: POLR2B].
RefSeq annotates one representative transcript (NM included in AceView variant.a), but Homo sapiens cDNA sequences in GenBank, filtered against clone rearrangements, coaligned on the genome and clustered in a minimal non-redundant way by the manually supervised AceView program, support at least 9 spliced variants.
One again, AceView notes that the annotated human genome has ignored the predicted alternative plice variants but maintains that there are at least nine of them.

Here's the figure, decide for yourself whether this is credible.


There are several well-known examples of human genes producing different protein variants due to alternative splicing. The ones I can think of off the top of my head are the genes for class I antigens, α-tropomyosin, and calcitonin. I'm sure there are half a dozen others.

Here's the challenge. See if you can find a human gene for a well-studied protein where the structure of the protein is known and there are multiple protein variants derived by alternative splicing. I bet that readers of Sandwalk can't find very many where the predicted variants many any sense and are likely to be biologically significant.

What does this mean? Whenever you look at your favorite well-studied gene you see that the predictions of alternative splicing are silly. So why should we believe the genome wide analyses? Is it just a coincidence that the more we learn about a given gene the most we become willing to reject the ESTs as artifacts? Or is it possible that alternative splicing is mostly confined to those genes that have not been well studied?