What is a gene, and what is it for?

ChromosomesThe gene is a fundamental concept in biology, and it has been since Mendel introduced it in the late 19th century, unbeknownst to Darwin, who was just at the same time looking for a theory of heredity, flirted with Lamarckism, and tiene came up with his own, incorrect, notion of blended inheritance.

Mendel’s work was rediscovered in 1900 (it’s bad for one’s academic career when one publishes in obscure journals and agrees to become an administrator, as the Augustinian friar did), and ever since it has been a crucial component of our understanding of biology. But scientists have developed a number of different concepts of gene, concepts that don’t always sit quite nicely and coherently with each other. Sounds like a job for philosophers of science…

And sure enough, a number of philosophers have written about genes and what they are “for” (including yours truly). By far the most active pair, however, is made of Paul Griffith and Karola Stotz, who have published a number of influential papers on gene concepts, and have now produced a new book on the topic, Genetics and Philosophy: An Introduction. Below I will comment on an in-depth essay about the book, published by Lindell Bromham (a biologist) in Biology and Philosophy. (Often book reviews in philosophy journals are a lot more than just book reviews, and provide the author a way to articulate his own thoughts on whatever subject matter is covered by the book.)

Before proceeding, one might well wonder what is the point of this sort of philosophical exercise. As Bromham puts it: “the word ‘gene’ belongs to all of us, and understanding its meaning is critically important for informed discussion of many important ideas in medicine, biology and in wider society. None of us is unconnected to debates about what is a ‘gene for’.”

One of the first things Bromham clarifies in his commentary is that common locutions such as “gene for bowel cancer” are nonsense. This is because of course genes don’t evolve (usually) to harm their carriers. What typically happens, though, is that we identify a gene when it misfire (say, contributing to causing bowel cancer), even though its normal function is something entirely different. It would be like trying to understand how cars work by studying when they break down and concluding that the brakes are “for” smashing into other cars when they unexpectedly cross your path.

Bromham correctly argues that one problem is that there is no common, i.e., non-technical, term to identify gene variants (the technical word is “allele”), so that people can make more sense of statements from doctors and other health care professionals: “So in most people the Huntington Disease gene does not give them Huntington’s Disease, only those people unlucky enough to inherit an allele of the gene with more than 40 repeats will get the disease.” Which means that people shouldn’t worry about whether they carry the gene “for” Huntington’s, but rather whether they have inherited a particular, lethal allele of a gene that does whatever it does when it works properly and causes Huntington’s when it doesn’t.

The bulk of the paper is then devoted to a section-by-section discussion of Griffith and Stotz’s classification of different concepts of genes, beginning, of course with the Mendelian one: “A mendelian ‘gene’ is a pattern of inheritance: it does not need to be a ‘gene’ in the sense of being a cistron [a DNA sequence that functions as an unbroken hereditary unit] that makes a product or influences phenotype.”

One of the complications is that sometimes blocks of cistrons (known as “haplotypes”) are inherited at once, perhaps because the individual genes making up the haplotype contribute to a particular biological function and natural selection therefore favored their inheritance as a larger, coherent unit (a “supergene”).

Then again, sometimes natural selection surprises biologists, as in the case of the mimicry in some species of butterflies, such as Papilio polytes. Their mimetic phenotype is the result of a coordinated action among a number of genes, so for a long time scientists thought these genes must be part of a single haplotype block and be inherited together, to maintain coordination. But no, it turns out that the whole shebang is orchestrated instead by a regulatory gene, known as doublesex, which sends signals to all the other genes involved in the production of the mimetic phenotype. No need for a supergene, if the work can be done by a single regulatory element.

As Bromham summarizes it: “Uncovering the rich complexity of gene action has not dissolved the mendelian gene, but it has disassociated the mendelian gene from any particular form of DNA sequence.” Moreover, there are genes whose influence is actually dependent on epigenetic factors, as in the case of the GNAS complex, defects in which are associated with a number of diseases in humans, including certain kinds of tumors. Some of these deleterious effects, however, are manifested only if the GNAS allele is inherited from the mother, while others take place only if the variant is inherited from the father. Not exactly a standard Mendelian factor.

There are also so-called “postgenomic genes,” which are defined as “the DNA sequences that have a linear correspondence to the gene product of interest, wherever these occur in the genome. This way you start with the product and work backwards to the DNA sequences that were needed for its construction. The ‘product’ is somewhat vague, as it will look different if we focus on the RNA transcript, a processed RNA molecule, or a translated protein.”

For instance, the above mentioned GNAS is actually a complex made of a whopping 17 different exons (transcribed units). The complex is controlled by a number of regulatory sequences, which cause differential “splicing” (i.e., different cuts off the larger molecule, resulting in different proteins after translation from the intermediate RNA). Some of these spliced versions are inherited maternally, other paternally, and yet others biparentally. Moreover, one of the exons can be “read” by the transcription enzymes in two different ways (two “reading frames,” in molecular biological jargon), resulting in two distinct proteins. What, exactly, constitutes a gene in the case of the GNAS complex?

Then we have the “reactive genome,” that is the ensemble of the gene that codes for a given protein plus the regulatory sequences that control when and where during the development or life of an organism the gene gets transcribed and then translated. This is affected by the environment, a term that includes not just the external conditions in which the organism happens to live, but also the intra-organismal one, such as which cells surround which others, their communication channels, and so forth.

Griffith and Stotz, and therefore also Bromham, also comment on the relationship between genes and the ever treacherous concept of information. The authors of the book — and Bromham seems to agree — correctly state that genes cannot really be said to be “coding” for anything other than sequences of amino acids (and not even that, in the case of many regulatory sequences). They certainly do not code for phenotypes, so that the phrase “gene for X” where X is the color of the eyes, a particular behavior, or whatever, is nonsensical from a strictly biological perspective: “in most usages, the use of the word ‘information’ to describe the functioning of genetic systems is at best a sloppy metaphor.”

Indeed, even the famous distinction between genotypes and phenotypes, which is at the center of simplistic metaphors such as Richard Dawkins’ “selfish gene” is undermined by advances in understanding within the field of molecular genomics. As Bromham puts it: “consider DNA sequences that do not act solely as a template but also act directly as a binding site for other molecules which recognize the particular sequence of nucleotides as a kind of ‘docking station’ … This means that DNA control elements that serve as recognition sequences are both genotype (a message that can be copied from one form to another) and phenotype (a structure that contributes to form and function).”

The last two sections of the paper address interesting questions concerning which I think Bromham comes across as reasonable but perhaps a bit too conservative.

The first one is dedicated to the issue of epigenetic inheritance. This is by now definitely a well established phenomenon in a number of organisms, but Bromham is right that the jury is still out there in terms of its long-term evolutionary significance. Most epigenetic variants are relatively short-lived, influencing phenotypes over the span of a few generations, very brief when compared to the stability of genetic sequences, whose shared ancestry is recognizable in organisms that have diverged for millions or even tens of millions of years. My take on this is that we have evidence at the moment that epigenetic inheritance can influence the short-term response of natural populations to environmental changes, but that long-term stability of phenotypes is encoded only in the DNA. This, however, doesn’t make the import of epigenetic factors negligible, since after all evolution happens one generation at a time (“evolutionary time” is simply the cumulation of a number of short moments), and because the epigenotype constantly interacts with the genetic system of inheritance, in highly non-linear and complex ways.

The last section of Bromham’s commentary concerns the so-called Extended Synthesis, the new version of evolutionary theory that some people (including yours truly, duly cited by Bromham) have been put forth in recent years, contrasting it with the standard Modern Synthesis.

Here is Bromham’s summary of the situation: “If ‘extended’ means a richer appreciation of the tangled web of interactions between genes, development and environment, then there are very few fields of biology that do not contribute to such an extension: the more we find out, the more we know, and the more fiendishly complicated everything looks … If ‘extended’ means that knowledge of the complex interactions between genotype and phenotype cannot be accommodated in current evolutionary theory, then there are no concrete examples here that illustrate how this new knowledge does not fit into the established framework.”

In my mind, “Extended” actually means something in between those extremes: neither trivial (like the first one), nor revolutionary (like the second one). But I’ve already explained my take on the ES vs MS debate elsewhere, so I will refer readers to that commentary.

151 thoughts on “What is a gene, and what is it for?

  1. synred

    I do think there is a difference in the case of using a word like ‘selfish’ in the title of a popular book and a word like ‘intentionality’ on a philosophy blog.

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  2. Coel

    Hi Robin,

    I think you might need to re read Massimo’s comment just above yours.

    Any particular reason why? I largely agreed with Massimo’s comment.

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  3. Coel

    Hi Robin,

    Did you seriously not understand why I suggested you re read his comment?

    Nope, I seriously did not understand why you suggested I re-read his comment. I’ve re-read it; I largely agree with it. I also stand by the comment you replied to.

    Maybe you overlooked the word “some” in “some philosophers”? It wasn’t a suggestion about *all* philosophers. The idea that *all* philosophers would ever agree on anything is as implausible as the idea that Nigel Farage and Jean-Claude Juncker would agree on the future direction of the EU! But that’s only a guess, so feel free to spell it out. (I really am simple like that, I do like things spelled out.)

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  4. Robin Herbert

    I am a little confused though. If we are saying genes are information in the same way that water is information, that seems a little trivial.

    And if we are talking about the various mathematical definitions of “information” like Shannon Information, then we are back to talking about the product of minds.

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  5. Coel

    Hi Robin,

    You are being mighty picky and pedantic if you’re claiming that the following implies that all philosophers think alike.

    “I’m going to take a wild stab here, based on my increasing appreciation of how philosophers think. In the eyes of **some** philosophers …”.

    The first sentence doesn’t have to be taken that way, and the “some” in the following sentence clearly indicates diversity of thought.

    From a quick Google:

    “What Do Philosophers Believe? – David Bourget and David J. Chalmers 2013

    “What Philosophers Think” Julian Baggini, 2005

    “What Philosophers Think” by Jeremy Stangroom (Editor). 2003

    Indeed: “What Do Philosophers Think?” — TPM Online by our very own Massimo

    None of these are taken to imply that all philosophers think alike. Maybe we can pick a more useful topic to discuss?

    Liked by 1 person

  6. Coel

    Hi Robin,

    If we are saying genes are information in the same way that water is information, that seems a little trivial.

    No, I would not say that “genes are information in the same way that water is information” and I would not make the bald context-free statement “water is information”. The meaning of “information” actually depends a lot on the context (the main point I’ve been emphasizing here). There is no one-size-fits-all meaning of “information” that suits all contexts.

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  7. brodix

    “Form,” is ideally static, even if applied to a fluid, or energy(water=water). In that if what was being referred to was changing/transitioning, it would be losing and or gaining forms.

    Such as information in information theory. The premise being how to transfer a message/information with the minimum of variation.

    Which is why it is not the same as the process/medium conveying it.

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  8. Philosopher Eric

    ‘Consciousness is how information feels when it’s being processed’

    Huh? I’m pretty sure information (of whatever sort) does not feel anything whether it’s being processed or not.

    Synred I’m pretty sure Tegmark meant that it’s the conscious subject that feels conscious, not the information it takes in. But wow, he said that? And without the use of my own model of the conscious mind? Interesting.

    I refer to the processing element of the conscious mind as “thought.” When you’re in pain for example, “thought” is the means by which you experience it, or the processing of such information. Thus you can’t be in pain when you’re not conscious given that you can’t think. Massimo’s iPad uses a non-conscious information processor however, or one that doesn’t “think.” In order for an iPad to be built that is conscious, at minimum Chalmer’s “hard problem” would need to effectively be overcome.

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  9. synred

    Click to access 0568.pdf

    Another interesting paper. Thanks!

    However, they fall early on into ‘intentional stance’ language.

    Although biological systems may be modeled with simplifying assumptions that lead to perfect adaptation, relaxation of these assumptions may yield an output that only adapts to within some tolerable range of the desired value.

    Desired by whom?

    Presumably they mean something more like just ‘tolerable range’ in the sense that the cell functions well enough. I would have just said ‘tolerable range’ and that the fixed value previously used was just an simplifying assumption.

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  10. Robin Herbert

    Hi Coel,

    Your words were:

    Anyhow, there’s nothing wrong with regarding DNA as information (it quite blatantly is, as physicists use the term).

    So DNA is qujte blatantly information as physicists use the term, and water is not information as physicists use the term.

    Certain molecules in a certain arrangement are information, as physicists use the term but other molecules in other arrangement are not?

    What is the distinction?

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  11. Massimo Post author

    Coel,

    “You are being mighty picky and pedantic if you’re claiming that the following implies that all philosophers think alike.

    “I’m going to take a wild stab here, based on my increasing appreciation of how philosophers think. In the eyes of **some** philosophers …”.”

    I took your sentence just in the same sense as Robin did. I guess your harping on philosophers and how they think has gotten to us, and we have subconsciously stopped giving you the benefit of the doubt…

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  12. Massimo Post author

    Robin

    “Certain molecules in a certain arrangement are information, as physicists use the term but other molecules in other arrangement are not?

    What is the distinction?”

    Right, that is indeed confusing, just like my example of rocks-as-calculators. For something to be information, I think, there has to be an apparatus that reads and uses such information. That apparatus can be conscious (humans) or not (ribosomes), but it can’t just be anything, on penalty of the word losing sense entirely.

    Liked by 2 people

  13. synred

    You might say DNA is not one molecule with an exactly the same atoms in exactly the same locations, but many similar molecules that can be arranged many different ways. The variations and that it can be copied make it ‘information’ — quite a lot of information.

    Water has little information whatever the homeopaths say. You might encode something in its excited states, but they’re not very stable and it wouldn’t last long, sitting on the shelf at your local health food store. Since they are strongly polarized a bunch might form short lived structures in your glass, but nothing useful.

    You could encode messages in ice ok patterned puddles on the floor, but the water molecule has effectively no information capacity.

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  14. synred

    Piles of rocks could and have been used as information in the ordinary sense. “This is my claim”. The information capacity of this mode of communication is limited! And there does need to be somebody to build the pile (prospector) and somebody to read it (claim jumper).

    Here the rules for California:

    California

    California Public Resources Code Section 3915.

    (a) The following are the only monuments which may be used pursuant to this chapter:

    (1) A wooden post not less than 1 1/2 inches in diameter projecting at least two feet above the ground.

    (2) A mound of stone projecting at least two feet above the ground. <–this one!

    (3) A nonperforated, capped metal post or solid metal rod, not less than one inch in diameter and projecting at least two feet above the ground.

    (b) Where, by reason of precipitous ground, it is impractical or dangerous to place a monument in its true position, a witness monument may be erected as near thereto as the nature of the ground will permit and marked so as to identify the true position.

    (c) Where, by reason of working the claim, it is impractical or dangerous to maintain a monument in its true position, a witness monument shall be erected as near thereto as the nature of the ground will permit and marked so as to identify the true position.

    (d) Any person using on January 1, 1992, or who has previously erected, any monument or object other than those defined in this section for the purposes of this chapter shall have until January 1, 1995, to comply with this section or remove those monuments which are not in compliance.

    (e) Within 180 days of abandonment, relinquishment, or loss of a, in effect on January 1, 1992, all monuments pertaining to that claim shall be permanently removed by the locator. A person who

    violates this subdivision shall be subject to a fine of not more than fifty dollars ($50) for each monument which is not removed and additionally liable for any cost incurred by the federal, state, or county government agency which removes any monument or has it removed.

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  15. brodix

    ” but the water molecule has effectively no information capacity.”

    That pretty much disqualifies 2/3 of the surface of the planet from having any information capacity.

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  16. Coel

    Hi Robin,

    … and water is not information as physicists use the term.

    No, I didn’t say that; I said it is context dependent. I can think of some physical contexts where water *would* count as “information”.

    But, one of the ways in which DNA blatantly is “information” is (in line with comments from Massimo and Synred) from the functional recipe point of view. DNA is translated into RNA and thence proteins which then build bodies. From that perspective the sequence of bases matters a lot. One can then talk about the number of bytes needed to encode the information content of that sequence.

    In many contexts there would be nothing equivalent regarding water, in that the layout of water molecules would be rapidly changing and mostly irrelevant, and from a functional perspective the information content would be vastly less. In such contexts “information” would be the wrong concept to apply.

    Liked by 2 people

  17. synred

    You could in principle encode information in the excited states or rotational states of water molecules. It would be fleeting though.

    Anything encoded by mixing in some poison and shaking would be long gone, before it reached the shelves of your local GNC, Whole Foods or Walgreens. Plain water is the ‘universal’ homeopathic remedy. And usually harmless, if you don’t live in Flint, MI.

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  18. synred

    Of course you can encode a message with water. Draw letters on the side walk with a watering can, or chisel a note in a piece of ice (could even last awhile in Moscow). Say, signs on bridges that say ‘slippery when icy’ that automatically remove themselves in the spring.

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  19. synred

    Up to 60% of the human adult body is water. According to H.H. Mitchell, Journal of Biological Chemistry 158, the brain and heart are composed of 73% water, and the lungs are about 83% water. The skin contains 64% water, muscles and kidneys are 79%, and even the bones are watery: 31%.May 2, 2016

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  20. garthdaisy

    I noticed some water dripping from my ceiling. This water conveyed to me the information that my roof has a leak. Water is information. 😉

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