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Tuesday, December 22, 2015

Waiting for multiple mutations: Michael Lynch v. Michael Behe

Casey Luskin is trying to help out a university student by describing some important ID contributions to science [No ID Research? Let's Help Out This Iowa State Student].

One of those contributions is a paper by Michael Behe and David Snoke published eleven years ago in Protein Science (Behe and Snoke, 2004). I described the result in a previous post: Waiting for multiple mutations: Intelligent Design Creationism v. population genetics.

If Behe & Snoke are correct then modern evolutionary theory cannot explain the formation of new functions that require multiple mutations.

Cassey Luskin is aware of the fact that this result has not been widely accepted. He mentions one specific criticism:
In 2008, Behe and Snoke's would-be critics tried to refute them in the journal Genetics, but found that to obtain only two specific mutations via Darwinian evolution "for humans with a much smaller effective population size, this type of change would take > 100 million years." The critics admitted this was "very unlikely to occur on a reasonable timescale."
He's referring to a paper by Durrett and Schmidt (2008). Those authors examined the situation where one transcription factor binding site was disrupted by mutation and another one nearby is created by mutation. The event requires two prespecified coordinated mutations.

Waiting for multiple mutations: Intelligent Design Creationism v. population genetics

Casey Luskin is worried about university students. Apparently, they aren't getting enough correct information about intelligent design. Luskin uses the example of a student named Michael Heckle at Iowa State University. Mr. Heckel said; "So far, there has been no research done by intelligent design advocates that has led to any sort of scientific discovery."

This happens to be a true statement but Casey Luskin takes exception in a blog post that appeared the other day on Evolution News & Views (sic) [No ID Research? Let's Help Out This Iowa State Student].

Saturday, December 19, 2015

Here's why Alain Beaudet, President of the Canadian Institutes of Health Research, should resign

The Canadian Institutes of Health Research (CIHR) is the main source of research funding for Canadian health researchers, including those doing basic research like most of the researchers in my biochemistry department.

A few years ago, CIHR decided to revamp the process of applying for and obtaining research grants. They did this without taking into consideration the wishes of most applicants. (They did "consult," but consulting isn't the same as listening.)

The result has been a disaster. Most researchers are confused and discouraged by the new process and there's great fear that the results of the next competitions will be harmful to basic research and harmful to new investigators.

But even before the new rules came into play the funding of basic, curiosity-motivated, science was taking a major hit. Many mid-career basic researchers at the University of Toronto have lost their grants or are struggling to make do with a lot less money. This is partly due to a lack of money in the system but it's been exacerbated by a deliberate shift in priorities under the previous Conservative government of former Prime Minister Stephen Harper.

These are some of the reasons why Canadian researchers have been calling for Alain Beuadet to resign [Support basic research with new leaders at the Canadian Institutes of Health Research (CIHR)].

Thursday, December 17, 2015

Joe Hanson tells us about evolution

Joe Hanson Ph.D. (Biology) of It's Okay To Be Smart is posting a series of videos on evolution. They're called The 12 Days of Evolution.

The first one is "What Is Evolution Anyway?" You won't surprised to learn that Joe Hanson conflates "evolution" with "natural selection" and fails to mention the most important features of evolution [see What Is Evolution]. You WILL be surprised to learn that Jerry Coyne has the same objections I do! [Twelve Days of Evolution: #1: What’s evolution?]

We need to do a much better job of educating the general public about the meaning of evolution but first we need to educate the teachers. It's okay to be smart but it's not okay to just pretend to be smart.

Strolling around slopes and valleys in the adaptive landscape

Another article about evolution and the attainment of perfection has appeared. This one was published by Nathaniel Scharping on the Discover website [Could Evolution Ever Yield a ‘Perfect’ Organism?].

The article focuses on a recent paper from Richard Lenski's group at Michigan State University (Lenski et al., 2015). Lenski's group asked a different question. They wanted to know whether there was a limit to the increase in fitness in their evolving E. coli populations in the Long-Term Evolution Experiment (LTEE). It's a different question than whether evolution can select for a "perfect" organism because Lenski and his collaborators understand modern evolutionary theory. They know that mutations causing small fitness increases are beyond the reach of natural selection in their evolving populations and they know that deleterious mutations can be fixed by random genetic drift.

They know that real evolving populations can never reach the summit of an adaptive peak or, if they do, they can never stay there.

Intelligent design explanations and speculations have all been refuted, discredited, or shown to be unnecessary

Intelligent Design Creationism is a movement based on bad science. Every single one of their positive, science-like, claims about ID have been refuted, or discredited, or shown to be completely unnecessary in the face of robust evolutionary explanations. Some of them have the distinction of being unnecessary AND refuted AND discredited (e.g irreducible complexity).

In addition to a small number of claims in support of ID, the proponents of Intelligent Design Creationism also advance dozens and dozens of arguments against evolution. In fact, this is by far the main activity of most adherents to the movement. Some of their arguments focus on legitimate scientific controversies. They are legitimate criticisms of some aspects of evolution but, even then, ID proponents often misrepresent and/or misunderstand the science behind the controversy (e.g. junk DNA).

However, the vast majority of their attacks on evolution are just as bad as their attempts to build a positive case for intelligent design. A disturbingly large number of such attacks exhibit a profound ignorance of science and how it works. In particular—surprisingly—they are ignorant of evolution. The movement is full of kooks. It will never become a credible source of information unless it purges itself by getting rid of the kooks.

Speaking of kooks,1 Casey Luskin has been publishing a series of articles on the Kitzmiller v. Dover trial that was decided ten years ago. Some of the articles make valid points but the latest one is a joke: Ten Myths About Dover: #4, "The Dover Ruling Refuted Intelligent Design".

You should read the article. It's a remarkable example of apologetics and why lawyers shouldn't try and explain science. While it's true that Judge Jones said lots of things we could quibble about, the big-picture take-home lesson from the trial is correct. No ID explanation stood up to the scrutiny of science. They were all shown to be either irrelevant or wrong.

That's why none of them should be presented in science class except as examples of bad science and faulty scientific reasoning.2

1. Luskin won't even admit that Young Earth Creationism is absurd.

2. In my opinion, they SHOULD be discussed in class since it's important to teach critical thinking and that requires that you directly confront common misconceptions.

Tuesday, December 15, 2015

How many different proteins are made in a typical human cell?

There are about 20,000 protein-coding genes in the human genome. Protein products for about 18,000 of these genes have been detected in at least one human tissue (Kim et al, 2015; Wilhelm et al., 2015) [see How many proteins do humans make?].

About 10,000 of these proteins are present in all cells (Wilhelm et al., 2015) and somewhere between 1500 and 2000 are derived from genes that are essential in the average human cell (Blomen et al., 2015; Wang et al, 2015; Hart et al., 2015) [see How many human protein-coding genes are essential for cell survival?].

Let's assume there are about 10,000 protein-coding genes that are expressed in a typical human cell. Does this mean that there are only 10,000 different proteins in those cells? The answer is "no" but the differences are often subtle. The activities of some proteins, for example, are regulated by covalent modification so a typical cell will contain different versions of the protein: some are modified and some are not (e.g. phosphorylated and non-phosphorylated). These would be genuine versions of different proteins although you probably wouldn't want to make a fuss about it.

In some cases, there are various intermediates produced during protein synthesis. For example, some proteins destined for the mitochondria have an N-terminal tag that's cleaved when the proteins reach their destination. There are two different versions of the protein but, again, this isn't really a big deal. We should really only count the steady-state, terminal, stage of processing and modification.

Similarly, there are proteins that are glycosylated in various ways and cells will always contain intermediates including non-glycosylated versions that have just entered the ER. These don't count as different versions of the protein.

Some genes are alternatively spliced to give proteins that have different internal amino acid sequences. These are genuinely different proteins produced from the same gene.

If you add up all the genuinely different versions of proteins produced from 10,000 protein-coding genes, how many proteins are present in a typical human cell?

Here's a standard answer given in a recent news article in Nature (Savage, 2015)
The human body contains roughly 20,000 genes that are capable of producing proteins. Each gene can produce multiple forms of a protein, and these in turn can be decorated with several post-translational modifications: they can have phosphate or methyl groups attached, or be joined to lipids or carbohydrates, all of which affect their function. “The number of potential molecules you can make from one gene is huge,” says Bernhard Küster, who studies proteomics at the Technical University of Munich in Germany. “It's very hard to estimate, but I wouldn't be surprised to have in one cell type 100,000 or more different proteins.”
I suspect that Küster is one of those scientists who think that almost all human protein-coding genes are alternatively spliced to yield several different proteins in each cell. He has to imagine that there are, on average, ten different versions of a protein produced from each gene that's expressed in a typical cell.

That means ten different versions of each of the subunits of pyruvate dehydrogenase and RNA polymerase. It means ten different versions of triose phosphate isomerase and each of the ribosomal proteins. There should be ten different versions of actin and ten different versions of cytochrome c.

This seems very unlikely to me.


(There may be a few genes that have thousands of different variants, although I'm skeptical. In that case there may be 100,000 different proteins in a human cell but surely this is misleading even if it's accurate?)

Blomen, V.A., Májek, P., Jae, L.T., Bigenzahn, J.W., Nieuwenhuis, J., Staring, J., Sacco, R., van Diemen, F.R., Olk, N., and Stukalov, A. (2015) Gene essentiality and synthetic lethality in haploid human cells. Science, 350:1092-1096. [doi: 10.1126/science.aac7557 ]

Hart, T., Chandrashekhar, M., Aregger, M., Steinhart, Z., Brown, K.R., MacLeod, G., Mis, M., Zimmermann, M., Fradet-Turcotte, A., and Sun, S. (2015) High-Resolution CRISPR Screens Reveal Fitness Genes and Genotype-Specific Cancer Liabilities. Cell 163:1515-1526. [doi: 10.1016/j.cell.2015.11.015]

Kim, M.-S., Pinto, S.M., Getnet, D., Nirujogi, R.S., Manda, S.S., Chaerkady, R., Madugundu, A.K., Kelkar, D.S., Isserlin, R., Jain, S., Thomas, J.K., Muthusamy, B., Leal-Rojas, P., Kumar, P., Sahasrabuddhe, N.A., Balakrishnan, L., Advani, J., George, B., Renuse, S., Selvan, L.D.N., Patil, A.H., Nanjappa, V., Radhakrishnan, A., Prasad, S., Subbannayya, T., Raju, R., Kumar, M., Sreenivasamurthy, S.K., Marimuthu, A., Sathe, G.J., Chavan, S., Datta, K.K., Subbannayya, Y., Sahu, A., Yelamanchi, S.D., Jayaram, S., Rajagopalan, P., Sharma, J., Murthy, K.R., Syed, N., Goel, R., Khan, A.A., Ahmad, S., Dey, G., Mudgal, K., Chatterjee, A., Huang, T.-C., Zhong, J., Wu, X., Shaw, P.G., Freed, D., Zahari, M.S., Mukherjee, K.K., Shankar, S., Mahadevan, A., Lam, H., Mitchell, C.J., Shankar, S.K., Satishchandra, P., Schroeder, J.T., Sirdeshmukh, R., Maitra, A., Leach, S.D., Drake, C.G., Halushka, M.K., Prasad, T.S.K., Hruban, R.H., Kerr, C.L., Bader, G.D., Iacobuzio-Donahue, C.A., Gowda, H., and Pandey, A. (2014) A draft map of the human proteome. Nature, 509:575-581. [doi: 10.1038/nature13302]

Savage, N. (2015) High-protein research. Nature 527:S6-S7. [doi: 10.1038/527S6a]

Wang, T., Birsoy, K., Hughes, N.W., Krupczak, K.M., Post, Y., Wei, J.J., Lander, E. S., and Sabatini, D.M. (2015) Identification and characterization of essential genes in the human genome. Science, 350:1096-1101. [doi: 10.1126/science.aac7041]

Wilhelm, M., Schlegl, J., Hahne, H., Gholami, A.M., Lieberenz, M., Savitski, M.M., Ziegler, E., Butzmann, L., Gessulat, S., Marx, H., Mathieson, T., Lemeer, S., Schnatbaum, K., Reimer, U., Wenschuh, H., Mollenhauer, M., Slotta-Huspenina, J., Boese, J.-H., Bantscheff, M., Gerstmair, A., Faerber, F., and Kuster, B. (2014) Mass-spectrometry-based draft of the human proteome. Nature, 509:582-587. [doi: 10.1038/nature13319]

Monday, December 14, 2015

Did Michael Behe say that astrology was scientific in Kitzmiller v. Dover?

Yes he did. But it doesn't mean what you think it means according to Casey Luskin [Ten Myths About Dover: #8, "Michael Behe Admitted that ID Is No More Scientific than Astrology"

I agree with Casey Luskin. During the trial, Behe was asked to define scientific theory and of course he adopted the broad view of science. He said, "Under my definition, a scientific theory is a proposed explanation which focuses or points to physical, observable data and logical inferences."

Here's the exchange that took place during the trial [Dover: Day 11].
Q In any event, in your expert report, and in your testimony over the last two days, you used a looser definition of "theory," correct?
A I think I used a broader definition, which is more reflective of how the word is actually used in the scientific community.
Q But the way you define scientific theory, you said it's just based on your own experience; it's not a dictionary definition, it's not one issued by a scientific organization.
A It is based on my experience of how the word is used in the scientific community.
Q And as you said, your definition is a lot broader than the NAS definition?
A That's right, intentionally broader to encompass the way that the word is used in the scientific community.
Q Sweeps in a lot more propositions.
A It recognizes that the word is used a lot more broadly than the National Academy of Sciences defined it.
Q In fact, your definition of scientific theory is synonymous with hypothesis, correct?
A Partly -- it can be synonymous with hypothesis, it can also include the National Academy's definition. But in fact, the scientific community uses the word "theory" in many times as synonymous with the word "hypothesis," other times it uses the word as a synonym for the definition reached by the National Academy, and at other times it uses it in other ways.
Q But the way you are using it is synonymous with the definition of hypothesis?
A No, I would disagree. It can be used to cover hypotheses, but it can also include ideas that are in fact well substantiated and so on. So while it does include ideas that are synonymous or in fact are hypotheses, it also includes stronger senses of that term.
Q And using your definition, intelligent design is a scientific theory, correct?
A Yes.
Q Under that same definition astrology is a scientific theory under your definition, correct?
A Under my definition, a scientific theory is a proposed explanation which focuses or points to physical, observable data and logical inferences. There are many things throughout the history of science which we now think to be incorrect which nonetheless would fit that -- which would fit that definition. Yes, astrology is in fact one, and so is the ether theory of the propagation of light, and many other -- many other theories as well.
Q The ether theory of light has been discarded, correct?
A That is correct.
Q But you are clear, under your definition, the definition that sweeps in intelligent design, astrology is also a scientific theory, correct?
A Yes, that's correct. And let me explain under my definition of the word "theory," it is -- a sense of the word "theory" does not include the theory being true, it means a proposition based on physical evidence to explain some facts by logical inferences. There have been many theories throughout the history of science which looked good at the time which further progress has shown to be incorrect. Nonetheless, we can't go back and say that because they were incorrect they were not theories. So many many things that we now realized to be incorrect, incorrect theories, are nonetheless theories.
Q Has there ever been a time when astrology has been accepted as a correct or valid scientific theory, Professor Behe?
A Well, I am not a historian of science. And certainly nobody -- well, not nobody, but certainly the educated community has not accepted astrology as a science for a long long time. But if you go back, you know, Middle Ages and before that, when people were struggling to describe the natural world, some people might indeed think that it is not a priori -- a priori ruled out that what we -- that motions in the earth could affect things on the earth, or motions in the sky could affect things on the earth.
I mostly agree with Behe.1 Astrology was an attempt to explain human behaviors by relating them to the position of the Earth on the day you were born. There is no connection. So today we think of astrology as bad science. It's not true that the stars determine your behavior and whenever we make this claim to an astologist we make sure to point out that the evidence is against it.

What we don't do is tell astrologers that they are entitled to believe whatever they want because astrology is not science and therefore we can't make a scientific statement about whether it's correct or not.

Intelligent Design Creationism is bad science. So is most of evolutionary psychology and some of genomics. So is the attempt to find god in a football helmet [The God Helmet: Your Brain on Religion].

It's disingenuous to make fun of Behe's testimony without understanding that the real issue is epistemology and the demarcation problem. Behe's view of science is perfectly legitimate but it didn't jibe with what the plaintiffs were trying to establish during the trial. They wanted to prove that ID isn't science and the best way to do that was to show that something can't be science unless it's true. In other words, science isn't a "way of knowing," it's the end result.

What does this mean? It means that every discredited attempt to explain something using science as a way of knowing becomes "not science" with hindsight. All those people who tried to show that genes were proteins were wrong so it means that what they were doing is not science. It means that of the two sides arguing about junk DNA, one of them will be wrong so, at some time in the future, their current activities will be seen as "not science."

Isn't that bizarre?

1. He should have been defining "science" not "scientific theory." That's the fault of his lawyers who failed to make this point during his direct testimony.

Did Kitzmiller v. Dover kill Intelligent Design Creationism?

The 10th anniversary of Judge Jone's decision in Kitzmiller v. Dover is coming up on Dec. 20, 2015. See the post at Panda's Thumb: Kitzmas is Coming!.

ID proponents are also marking the event in various ways. If you are interested in the discussion, you should read the posts on Evolution News & Views covering the Ten Myths about Dover. The first one (#10) is Ten Myths About Dover: #10, "The Intelligent Design Movement Died After the Dover Decision".

Of course the ID movement didn't die after Kitzmiller v. Dover. From the outside (i.e. not in the USA) it seems to be as strong as ever. State legislatures all over America are still trying to suppress the teaching of evolution and promote creationist perspectives. The movement has captured the attention of many (most?) prominent politicians and much of the American public still believes that scientists are wrong about evolution.

Friday, December 11, 2015

A "synthetic" view of the Modern Synthesis

I just re-read a 1997 paper by Francis Ayala and Walter Fitch (Ayala and Fitch, 1997). The opening two paragraphs describe the Modern Synthesis of Evolution in a very interesting way. The emphasis is on the history and the contributions of Theodosius Dobzhansky (1900-1975) but it makes another point that I'd like to mention.
Theodosius Dobzhansky (1900–1975) was a key author of the Synthetic Theory of Evolution, also known as the Modern Synthesis of Evolutionary Theory, which embodies a complex array of biological knowledge centered around Darwin’s theory of evolution by natural selection couched in genetic terms. The epithet ‘‘synthetic’’ primarily alludes to the artful combination of Darwin’s natural selection with Mendelian genetics, but also to the incorporation of relevant knowledge from biological disciplines. In the 1920s and 1930s several theorists had developed mathematical accounts of natural selection as a genetic process. Dobzhansky’s Genetics and the Origin of Species, published in 1937 (1), refashioned their formulations in language that biologists could understand, dressed the equations with natural history and experimental population genetics, and extended the synthesis to speciation and other cardinal problems omitted by the mathematicians.

The current Synthetic Theory has grown around that original synthesis. It is not just one single hypothesis (or theory) with its corroborating evidence, but a multidisciplinary body of knowledge bearing on biological evolution, an amalgam of well-established theories and working hypotheses, together with the observations and experiments that support accepted hypotheses (and falsify rejected ones), which jointly seek to explain the evolutionary process and its outcomes. These hypotheses, observations, and experiments often originate in disciplines such as genetics, embryology, zoology, botany, paleontology, and molecular biology. Currently, the ‘‘synthetic’’ epithet is often omitted and the compilation of relevant knowledge is simply known as the Theory of Evolution. This is still expanding, just like one of those ‘‘holding’’ business corporations that have grown around an original enterprise, but continue incorporating new profitable enterprises and discarding unprofitable ones.
The important point here is that evolutionary theory is a complex synthesis of sub-theories, hypotheses, and observations. While it may be convenient to refer to this synthetic version as the "Theory of Evolution," it's also very misleading.

I strongly recommend that we abandon that term and use "evolutionary theory" instead. Furthermore, we should be careful about using the term "Modern Synthesis" unless we are specifically referring to the version of evolutionary theory that was popular in the 1950s.

It's true that Ayala and Fitch would like to retain the term "Synthetic Theory" to refer to the expanded version of the Modern Synthesis. They want to emphasize that there have been important extensions to the original Modern Synthesis but these are merely add-ons. Darwin's basic idea of evolution by natural selection remains at the core of their version of the "Theory of Evolution."

That seems like a very pluralistic view but I'd like to note several things about this paper.
  1. The word "drift" appears only once and it's in the form "neutral drift." There's no mention of random genetic drift as a mechanism of evolution that's been incorporated into the synthetic version of evolutionary theory.
  2. The word "neutral" appears five times but "Neutral Theory" is not mentioned. The authors do concede that "the neutral-selection controversy rages on."
  3. There are 50 references but not a single paper by Mootoo Kimura is mentioned. They do, however, discuss molecular clocks and discuss whether amino acid substitutions are really of "no adaptive consequence."
  4. There's a fairly well-known paper by Gould and Lewontin that might be relevant in a discussion about the synthetic version modern evolutionary theory. They neglected to mention it.

Ayala, F.J., and Fitch, W.M. (1997) Genetics and the origin of species: an introduction. Proc. Natl. Acad. Sci. (USA) 94:7691-7697. [PDF]

Gould, S.J., and Lewontin, R.C. (1979) The spandrels of San Marco and the Panglossian paradigm: a critique of the adaptationist programme. Proc. Roy. Soc. (London) Series B. Biological Sciences 205:581-598. [doi: 10.1098/rspb.1979.0086]

Thursday, December 10, 2015

How many human protein-coding genes are essential for cell survival?

The human genome contains about 20,000 protein-coding genes and about 5,000 genes that specify functional RNAs. We would like to know how many of those genes are essential for the survival of an individual and for long-term survival of the species.

It would be almost as interesting to know how many are required for just survival of a particular cell. This set is the group of so-called "housekeeping genes." They are necessary for basic metabolic activity and basic cell structure. Some of these genes are the genes for ribosomal RNA, tRNAs, the RNAs involved in splicing, and many other types of RNA. Some of them are the protein-coding genes for RNA polymerase subunits, ribosomal proteins, enzymes of lipid metabolism, and many other enzymes.

The ability to knock out human genes using CRISPR technology has opened to door to testing for essential genes in tissue culture cells. The idea is to disrupt every gene and screen to see if it's required for cell viability in culture.

Three papers using this approach have appeared recently:
Blomen, V.A., Májek, P., Jae, L.T., Bigenzahn, J.W., Nieuwenhuis, J., Staring, J., Sacco, R., van Diemen, F.R., Olk, N., and Stukalov, A. (2015) Gene essentiality and synthetic lethality in haploid human cells. Science, 350:1092-1096. [doi: 10.1126/science.aac7557 ]

Wang, T., Birsoy, K., Hughes, N.W., Krupczak, K.M., Post, Y., Wei, J.J., Lander, E. S., and Sabatini, D.M. (2015) Identification and characterization of essential genes in the human genome. Science, 350:1096-1101. [doi: 10.1126/science.aac7041]

Hart, T., Chandrashekhar, M., Aregger, M., Steinhart, Z., Brown, K.R., MacLeod, G., Mis, M., Zimmermann, M., Fradet-Turcotte, A., and Sun, S. (2015) High-Resolution CRISPR Screens Reveal Fitness Genes and Genotype-Specific Cancer Liabilities. Cell 163:1515-1526. [doi: 10.1016/j.cell.2015.11.015]
Each group identified between 1500 and 2000 protein-coding genes that are essential in their chosen cell lines.

One of the annoying things about all three papers is that they use the words "gene" and "protein-coding gene" as synonyms. The only genes they screened were protein-coding genes but the authors act as though that covers ALL genes. I hope they don't really believe that. I hope it's just sloppy thinking when they say that their 1800 essential "genes" represent 9.2% of all genes in the genome (Wang et al. 2015). What they meant is that they represent 9.2% of protein-coding genes.

By looking only at genes that are essential for cell survival, they are ignoring all those genes that are specifically required in other cell types. For example, they will not identify any of the genes for olfactory receptors or any of the genes for keratin or collagen. They won't detect any of the genes required for spermatogenesis or embryonic development.

What they should detect is all of the genes required in core metabolism.

The numbers seen too low to me so I looked for some specific examples.

The HSP70 gene family encodes the major heat shock protein of molecular weight 70,000. The protein functions as a chaperone to help fold other proteins. They are among the most highly conserved genes in all of biology and they are essential. The three genes for the normal cellular proteins are HSPA5 (Bip, the ER protein); HSPA8 (the cytoplasmic version); and HSPA9 (mitochondrial version). All three are essential in the Blomen et al. paper. Only HSPA5 and HSPA9 are essential in Hunt et al. (This is an error.) (I can't figure out how to identify essential genes in the Wang et al. paper.)

There are two inducible genes, HSPA1A and HSPA1B. These are the genes activated by heat shock and other forms of stress and they churn out a lot of HSP70 chaperone in order to save the cells. There are not essential genes in the Blomen et al. paper and they weren't tested in the Hunt et al. paper. This is an example of the kind of gene that will be missed in the screen because the cells were not stressed during the screening.

I really don't like these genomics papers because all they do is summarize the results in broad terms. I want to know about specific genes so I can see if the results conform to expectations.

I looked first at the genes encoding the enzymes for gluconeogenesis and glycolysis. The results are from the Blomen et al. paper. In the figure below, the genes names in RED are essential and the ones in blue are not.

As you can see, at least one of the genes for the six core enzymes is essential. But none of the other genes is essential. This is a surprise since I expect both pathways (gluconeogenesis and glycolysis) to be active and essential in those cells. Perhaps the cells can survive for a few days without making these enzymes. It means they can't take up glucose because one of the hexokinase enzymes should be essential.

These result suggest that the Blomen et al. study is overlooking some important essential genes.

Now let's look at the citric acid cycle. All of the enzymes should be essential.

That's very strange. It's hard to imagine that cells in culture can survive without any of the genes for the subunits of the pyruvate dehydrogenase complex or the subunits of the succinyl C0A synthetase complex. Or malate dehydrogenase, for that matter.

Something is wrong here. The study must be missing some important essential genes. I wish the authors had looked at some specific sets of genes and told us the results for well-known genes. That would allow us to evaluate the results. Perhaps this sort of thing isn't done when you are in "genomics" mode?

The "core fitness" protein-coding genes that were identified are more highly conserved than the other genes and they tend to be more highly expressed. They also show lower levels of variation within the human population. This is consistent with basic housekeeping features.

Each group identified several hundred unannotated genes in their core sample. These are genes with no known function (yet).

The results of the three studies do not overlap precisely but most of the essential genes were common to all three analyses.

Wednesday, December 09, 2015

Why doesn't natural selection reduce the mutation rate to zero?

All living organisms have developed highly accurate DNA replication complexes and sophisticated mechanisms for repairing DNA damage. The combination results in DNA replication errors that are about 1 per 10 billion base pairs (10-10 per bp). DNA damage due to other factors is effectively repaired with an error rate of 1 in 100 per base pair (10-2 per bp).

Mutations can be beneficial, deleterious, or neutral. In organisms with large genomes there are many more neutral mutations than the other two classes but in organisms with smaller genomes a higher percentage of mutations are either beneficial or deleterious. In all cases, there are more deleterious mutations than beneficial ones.

If deleterious mutations are harmful to the individual then natural selection should favor a low mutation rate in order to minimize that effect. This is especially true in large multicellular organisms where somatic cell mutations cause cancer and other problems. It seems logical that the optimal mutation rate should be zero in order to maximize the survival of the individual and its offspring.

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

Michael Lynch
But even though the number of beneficial mutations is low compared to those that are deleterious, this is the stuff of adaptive evolution. In the long run the population will become more fit if beneficial mutations occur and become fixed by natural selection. Eliminating mutations might provide a short-term advantage but eventually the population will go extinct if it can't adapt to new environments. (Neutral and deleterious mutations can also contribute to adaptation over the long term.)

The simplest explanation for this apparent paradox is that there's a trade-off between selection to minimize deleterious mutations and selection for long-term evolutionary advantage. The problem with that explanation is that it is very difficult to show how you can select for the future benefit of mutations to the species (population). It seems as though you have to invoke two bogeymen; group selection and teleology.

Maybe there's a better explanation?

Jerry Coyne recently thought about this problem and posted his analysis under the provocative title: The irony of natural selection. He concludes that there's some constraint that limits the ability of natural selection to achieve a zero mutation rate.
The most probable explanation is that evolution does not produce perfect adaptations. In the case of mutations, though natural selection favors individuals most able to repair any changes in DNA (although a small percentage of these might be adaptive), this level of perfection cannot be achieved because of constraints: the cost of achieving perfection, the fact that all errors are impossible to detect or remove, or that some cells (i.e., sperm or eggs) may not even have DNA-repair mechanisms because of genetic or physiological constraints.
I used to think that this was the best explanation. I taught my students that the accuracy of DNA replication, for example, comes at the cost of speed. The more accurate the polymerization process, the slower it takes. This makes a lot of sense and there's experimental support for the claim. Slowing down the time it takes to replicate the genome will affect the time it takes for cell divisions and that could be harmful ... or so the argument goes.

Unfortunately, I ran into Michael Lynch at an evolution meeting and he quickly destroyed that argument. There's no evidence that the speed of DNA replication is limiting the rate of cell divisions and, besides, there are easy ways for selection to get around such a limitation if it ever occurred. (This is a photo of Michael Lynch looking at me right after setting me straight. He's wondering how I could have been so stupid.)

When you think about it, there doesn't seem to be any biochemical or physiological constraints that could prevent the mutation rate from getting to zero ... or at least a lot closer than it is now.

Michael Lynch has a better answer and he explains it in a paper titled: "The Lower Bound to the Evolution of Mutation Rates" (Lynch, 2011).
As the mutation rate is driven to lower and lower levels by selection, a point must eventually be reached where the advantage of any further increase in replication fidelity is smaller than the power of random genetic drift (Lynch 2008, 2010). The goal here is to evaluate the extent to which such an intrinsic barrier can provide an adequate explanation for the patterns of mutation rates known to have evolved in natural populations.
The main "constraint" is the limited power of natural selection in the presence of random genetic drift. This will depend to some extent of the size of the population.

This idea is called the "drift-barrier hypothesis. It is described in Sung et al. (2012):
... the drift-barrier hypothesis predicts that the level of refinement of molecular attributes, including DNA replication fidelity and repair, that can be accomplished by natural selection will be negatively correlated with the effective population size (Ne) of a species. Under this hypothesis, as natural selection pushes a trait toward perfection, further improvements are expected to have diminishing fitness advantages. Once the point is reached beyond which the effects of subsequent beneficial mutations are unlikely to be large enough to overcome the power of random genetic drift, adaptive progress is expected to come to a standstill. Because selection is generally expected to favor lower mutation rates as a result of the associated load of deleterious mutations, and because the power of drift is inversely proportional to Ne, lower mutation rates are expected in species with larger Ne.
The Lynch lab has produced lots of evidence in support of the hypothesis although there may be some confounding factors in some populations.

The bottom line is that the real irony of natural selection is that it's just not powerful enough to reduce the error rate of replication and repair below the values we currently see.

In a sense, it's the "error rate" of fixation by natural selection in the face of random genetic drift that allows evolution to occur.

The more we learn about biology the more we learn that it's messy and sloppy at every level. Evolution is not a watchmaker and it's not even a blind watchmaker. It's a tinkerer1 and the "watch" barely keeps time.

Image Credit: The Mendel's traits image is from Wikispaces Classroom.

1. Jacob, F. (1977) Evolution and tinkering. Science (New York, NY), 196:1161. [PDF]

Lynch, M. (2011) The lower bound to the evolution of mutation rates. Genome Biology and Evolution, 3:1107. [doi: 10.1093/gbe/evr066]

Sung, W., Ackerman, M.S., Miller, S.F., Doak, T.G., and Lynch, M. (2012) Drift-barrier hypothesis and mutation-rate evolution. Proc. Natl. Acad. Sci. (USA) 109:18488-18492. [doi: 10.1073/pnas.1216223109]

Thursday, December 03, 2015

Facts and theories of evolution according to Dawkins and Coyne

Sometime back in the pre-Cambrian (before blogs) there was a newsgroup called—it still exists. In 1993 I wrote a little essay that tried to convince creationists1 of the difference between facts of evolution and evolutionary theory [Evolution is a Fact and a Theory]. I relied heavily on Stephen Jay Gould's essay on "Evolution as Fact and Theory" originally published in Discover magazine in 1981 and re-printed in Hen's Teeth and Horse's Toes.

I updated my thoughts on Gould's essay in 2007 [Evolution Is a Fact and a Theory] and added some more comment on the 30th anniversary [Evolution Is a Fact and a Theory].

Lot's of other people have presented their take on the facts and theories of evolution. Here's one from Richard Lenski and another from Ryan Gregory.

Monday, November 30, 2015

Celebrating Lucy Maud Montgomery

Today Google celebrates the birthday of Lucy Maud Montgomery (November 30, 1874 – April 24, 1942). She is the author of Anne of Green Gables and other books.

Lucy Maud Montgomery was born in Prince Edward Island (Canada) and after getting her teaching certificate from Prince of Wales College in Charlottetown (P.E.I.) she attended Dalhousie University in Halifax (Nova Scotia, Canada) before taking up a teaching position in P.E.I. That's when she wrote Anne of Green Gables (1908).

In 1911 she married a Presbyterian minister, Ewen Macdonald, and moved to Uxbridge, Ontario (northeast of Toronto). In 1926, she and her husband moved to Norval, Ontario, a small village due north of where I live in Mississauga, Ontario. We've passed her house many times. She lived there until 1935 when she moved to Swansea, Ontario, now a part of western Toronto between the Humber River and High Park. She died there in 1942 and was buried in P.E.I.

Lucy Maud Montgomery is a distant cousin of mine. I descend from the Coles. The genealogy is confusing but at some point in time a Mr. Cole and his wife Mary (maiden name unknown) came to North America, probably New York. Their son, Benjamin Cole, is my great4-grandfather. Mr. Cole died sometime around 1765 and Mary married George Penman. The history is confusing, they may have lived in New England and moved to P.E.I. just before or after the American Revolution. They self-identify as United Empire Loyalists.

Mary is my great5 grandmother and she had several children with George Penman. Two of them were Nancy (b. 1768) and Elizabeth ("Betsy") (b. 1769). Nancy married Donald Montgomery of the "New Moon" farm in Malpeque, P.E.I. (Emily of New Moon). Her sister married David Murray.

Donald Montgomery, the son of Nancy & Donald, married his first cousin Ann Murray, daughter of Elizabeth & David. Their son, Hugh John Montgomery, was Lucy Maud Montgomery's father.

Thus, Lucy Maud Montgomery's great grandmother is my great-great-great-great-great grandmother.

Sunday, November 29, 2015

Motoo Kimura calculates a biochemical mutation rate in 1968

I recently had occasion to re-read a paper by Motoo Kimura from 1968. (Kimura, 1968). I noticed, for the first time, that he estimates a mutation rate based on his understanding of the error rate of DNA replication. He also makes a comment about creationists.

Remember, this was in 1968 and we didn't know as much then as we do now. Kimura took note of the fact that evolutionary trees based on comparing amino acid sequences gave rates of amino acid substitutions that seemed far too high. His conclusion is in the abstract.

Friday, November 27, 2015

Hawker Hurricanes and Typhoons in World War II

Last week we went to the Canadian Warplane Heritage Museum in Hamilton, Ontario (Canada) with our grandson Luca [see The Latest Excursion]. Here I am with Luca standing beside a Hawker Hurricane from World War II.

My father, F/L Laurence Victor "Vic" Kirsch,1 was a fighter pilot in World War II and he flew Hurricanes and, later, rocket-firing Hawker Typhoons with the RAF 164 Squadron known as the Argentine British Squadron because of the volunteers from Argentina. (My father was seconded from the RCAF (Canada)).

Here's a picture of him (below) in the cockpit of one of his planes.

I have his log books. The first page (right) shows him flying Hurricanes ("Hurry") in sorties over France in December 1943. This was just when the squadron was preparing to switch to Typhoons and become specialists in ground support in preparation for D-Day.

The next entries (below) are facing pages from June, 1944. Note the entry for June 6, 1944. On the left is "DER TAG" in red and on the right is "LONG AWAITED 2nd FRONT IS HERE." The entry for June 5th reads, "Deas and self flew to Cherbourg and reported the weather. Flew over the invasion fleet, impressive sight. Hundreds of naval craft and A/C cover. Wouldn't have missed this sight for the world. Dark when we landed and silly old Deas practised landing on his belly."

The entry for June 6th (D-Day) reads, "Followed SQDN across channel. Saw hundreds of ships. Jumped by 90's."

On June 14th (one week after D-Day) the squadron lands at their new base in Crépon, France.

1. He died in a plane crash when I was four months old. My mother remarried and I was adopted by my stepfather, K.R. Moran.

Thursday, November 26, 2015


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
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
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. (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]