Image credit: DALL-E and Norman’s Woe
In the cave, there were gold, silver, and all kind of treasures. Among those was a magic lamp glowing in the dark. Aladdin took the Magic lamp and tried to get out of the cave. The wizard asked Aladdin for the lamp but he asked the wizard to fetch him out first. But the angry wizard closed the cave door and went. Aladdin accidentally rubbed the lamp, a genie appeared.
– Aladdin and the Magic Lamp, author unknown
As reading can become tiresome, instead of a thousand words:
Everyone knows what they’re writing about, right? Genes. And readers know what they’re reading about, right? Genes.
Having seen those headlines almost incessantly (like insurance commercials), perhaps even having read one of the news articles, you might have paused and thought to yourself (which by itself is strange–but that’s a different issue entirely): What exactly is a gene? You search your lizard brain for a memory from the biology class you inevitably took, long ago. You even once struggled through Dawkin’s The Selfish Gene, back before you had so many demands on your time.
Nope, no luck. So you consult your external memory machine: the web. And, as you’ve become increasingly careful to look for authoritative sources, you click the link to Encyclopedia Britannica. What could be more authoritative than that? Whereupon you read the following:
Gene, unit of hereditary information that occupies a fixed position (locus) on a chromosome. Genes achieve their effects by directing the synthesis of proteins.
Ah, of course. Now I remember, you think. You study the accompanying illustration carefully (which cannot be shown here, as it’s copyrighted by the esteemed publication). Yes, you think, that’s it.
Feeling particularly (perhaps unusually) inquisitive, you further ask yourself, And what exactly do proteins do? Click, click…:
Proteins are essential for life and are essential for a wide range of cellular activities. Protein enzymes catalyze the vast majority of chemical reactions that occur in the cell. Proteins provide many of the structural elements of a cell, and they help to bind cells together into tissues. Proteins, in the form of antibodies, protect animals from disease, and many hormones are proteins. Proteins control the activity of genes and regulate gene expression.
Got it, you think. Proteins (among other things) create tissues; you are a collection of tissues. Putting it all together you imagine the following formula:
chromosome > DNA > gene > proteins > tissues > me (!)
Feeling pleased with yourself (again, strange, but a habit of yours), your lizard brain reminds you that you have a tee time scheduled. Hurry, you’re running late.
Richard Dawkins needs no introduction. His seminal The Selfish Gene catapulted the concept of gene into popular consciousness and introduced the concept meme.1 Scientific reception was mixed, tilting toward negative,2 but it was a popular hit, selling over one million copies and translated into over 20 languages. Presumably, some percentage of the million copies was actually read, including one by you, long long ago.
But you don’t remember much of it. If you did, and if you had read it seriously enough to have been persuaded, you would think a great deal less of yourself than you likely do. That alone would be worth the million copies sold.
Dawkins presents the central question of the book:
Evolution works by natural selection, and natural selection means the differential survival of the ‘fittest’. But are we talking about the fittest individuals, the fittest races, the fittest species, or what?3
The answer comes a bit further along:
I shall argue that the fundamental unit of selection, and therefore of self-interest, is not the species, nor the group, nor even, strictly, the individual. It is the gene, the unit of heredity.4
For Dawkins, you are nothing more than a “vehicle” for your genes. Or, more pithily, a “survival machine” for replicators—DNA molecules. Genes are the appropriate unit of Darwinian selection.
To be fair to Dawkins, he wasn’t all that happy about what he was arguing. He was frank in stating that living in a society based solely on the gene’s “law of universal ruthless selfishness” would be a “nasty” existence. And while explicitly stating that he was not advocating a morality based on evolution or suggesting how humans morally ought to behave, he gave a moralizing caution:
Be warned that if you wish, as I do, to build a society in which individuals cooperate generously and unselfishly towards a common good, you can expect little help from biological nature. Let us try to teach generosity and altruism, because we are born selfish. Let us understand what our own selfish genes are up to, because we may then at least have the chance to upset their designs, something that no other species has ever aspired to.5
The 20th century has been called “the century of the gene,” and Dawkins adopted its classical molecular gene concept, also known as the “central dogma,” without elaboration. And you really can’t blame him, as first, the dogma was widely endorsed (as dogmas are wont to be); second, the framework produced great advances in a wide range of scientific disciplines; and third, he was a young man.6
In the classical model, a gene was a physical entity with a structure and a function. Its structure was an identifiable stretch of DNA with a physical beginning and end. Its function was to encode a product, such as a polypeptide chain (the building blocks of the proteins that knit your bones and sinews) or RNA molecule.7
Clear, simple, straightforward. No room for confusion. In fact, American in its simplicity, pragmatism and applicability: the gene is the business owner, mRNA the supply chain, ribosomes the factory, and proteins the product—the killer app. Genes = job creators!
Which led to the notion of genetic determinism—and not only among the great unwashed (including the scientific media), but among the “overgrown children still to be found among our scientists”8 as well. There’s a gene for that.
To its credit, the classical molecular gene concept allowed geneticists and biologists of various sorts (molecular, developmental) to make significant gains in understanding how you become you and continue to become you over your lifespan, for good or ill. All the better if for ill, as, beyond extending human understanding of how things work, products could be created to cure you (or give you a bit more time, on average)—attracting all manner of funding for development (public and private) and ultimately record-shattering IPOs.
In their excitement, geneticists and their ilk may have over egged the pudding a bit by alluding to miraculous cures on the horizon for any number of gene-related maladies you might suffer (firing up the scientific press accordingly), only to discover over time that … it’s complicated.9
Unease with the central dogma grew as more was learned about genetic material. The boundaries of molecular genes became ever less clear as all manner of confounding things were observed. Like alternative splicing: a gene can code for more than one protein, which it would almost have to do as there are an estimated 90,000 human proteins and the Human Genome Project estimated only 30,000 to 40,000 genes.10 If a gene only coded for one protein, as the central dogma maintained, where do all the other proteins come from? This is known as the one-to-many problem.
Another confound was the discovery that multiple nucleotide sequences (the building blocks of DNA) can code for the same amino acid sequence (the building block of proteins). So it’s not one gene for one protein; the same protein can have multiple authors. This is known as the many-to-one problem.
A third is the phenomenon where there is no direct relationship between a segment of DNA and the polypeptide or RNA that it encodes, which can occur due to post-transcriptional modifications to RNA. Post-transcriptional modifications? Mistakes? No, the modifications are essential for the production of a functional RNA molecule, which can result in the production of different polypeptides from the same mRNA. This is known as the lack of correspondence problem.
Those are the big three, but many other confounds emerged. Genes can overlap, one gene can be nested in another…. The list goes on and on, and only grows as more is learned.
Including the teeny weenie problem that genes don’t do … anything.11 Not by themselves anyway. They are subject to regulation (which job creators throughout the Union—Texans most of all—will find an outrage). They must be expressed to code for proteins (do something); they can be suppressed.
A common metaphor for a gene is a recipe which has to be copied (transcribed) to RNA for anything useful to happen—such as making proteins, which do pretty much all the heavy lifting for living organisms. And like a recipe, they’re not so smart. They can’t decide when to transcribe; that would be “like saying a recipe decides when a cake is baked.”12 And what regulates transcription? The environment, or better environments: from the environment within your cells, to the spaces between your cells, to the environment your whole body constitutes—to the outside world. Enter epigenetics.13
All of this created a crisis in genetics, leading to articles with titles such as, “Between the cross and the sword: The crisis of the gene concept.”14 It turns out that nobody agrees on just what a gene is. Some researchers have concluded genes don’t exist (as a physical entity, anyway; maybe it’s a process, maybe a domain, maybe a sign; see “Handy table” below). Because, if they exist at all, genes exhibit all kinds of strange behavior beyond mechanically coding for proteins (thus your bones and sinews).
Like the word “love,” everyone uses the term gene, but it means different things to different people in different contexts. And like the word “love,” no one can stop using it. The only thing one can be sure of is that a gene is certainly not “a stretch of DNA that encodes a functional product, a single polypeptide chain or RNA molecule.”
The dogma had crumbled under the weight of its own simplicity.
And what, you ask, does any of this matter? Uh … what a question. What does anything matter? Except that you are made of proteins, so you might want to know something about what is known (and not known) about that, which is to say about you, which is of course your favorite subject. There.
More likely than not, you’ll revert to your original understanding of gene, the one you read so long ago in Dawkins (and then forgot): a gene is an identifiable thing (and a selfish one at that) that does one specific thing. Which makes all the sense in the world of genetic determinism: there’s a gene for that (the antecedent of that being what you will: eye color, multiple sclerosis, homosexuality, your laudable generosity…). “They are in you and in me; they created us, body and mind….”15
Turns out that Dawkins’s selfish gene was more of a genie. Maybe time to toss that—and the thing it came in?
Unlikely. It’s a good bet that nothing will move you to reconsider, think harder, or update your credences:
[G]enetics teaching in two different universities did not have much consequence regarding changes in the prevalence of the commitment to the classical molecular gene [among biological and medical students] … even after explicit teaching about the crisis of the gene concept and the proposals to overcome it….16
Alternatively, you might pause long enough to consider that things can be complicated, that “known” facts—even dogmas—only speak to one moment in time and are ever subject to challenge, revision, sometimes abandonment. When it comes to figuring out how things work, the best that can be said is “as far as we currently know.”17
Handy table
Genes and whether to keep, modify or drop the concept, after Meyer et al., op. cit., 369-70.
| Views | Explanation | Keep, drop, modify |
| Classical molecular gene concept (Griffiths and Neumann-Held 1999; Stoltz et al. 2004) | A stretch of DNA that encodes a functional product, a single polypeptide or RNA molecule Genes as structural, functional and informational units | – Keep – |
| Crisis of the gene concept–anomalies challenging the classical molecular gene concept (Pardini and Guimarães 1992; El-Hani 2007) | Three kinds of anomalies and their consequences for a unitary relationship between genes, gene products and gene function: (i) alternative splicing, a single gene codes for multiple proteins (ii) changes in the structure of an organism’s DNA (genomic rearrangements) (iii) lack of correspondence between DNA segments and RNAs/polypeptides; information in DNA isn’t always directly and exactly converted into RNA and then into proteins | – Modify – |
| Process molecular genes (Griffiths and Neumann-Held 2001) | Genes as the recurring process that leads to the temporally and spatially regulated expression of a particular polypeptide product | – Modify – |
| Gene-P (Moss 2001, 2003a) | Gene as determinant of phenotypes or phenotypic differences Statements in the form of “X is a gene for Y, human disorder or trait Instrumental concept, not accompanied by hypothesis of correspondence to reality Not to be conflated with gene-D | – Modify – |
| Gene-D (Moss 2001, 2003a) | Gene as developmental resource, real entity defined by molecular sequence in DNA Developmental resource for the construction of traits, along with equally important resources (epigenetic and environmental factors) Does not determine phenotypic trait Not to be conflated with gene-P | – Modify – |
| Genes as sets of domains in DNA (Fogle 1990, 2000) | Genes constructed from assemblage of embedded and overlapping domains in DNA Domains are nucleotide (building blocks of DNA & RNA) sequences distinguished by structural properties and/or activities | – Modify – |
| Systemic gene concept (Pardini and Guimarães 1992) | Gene as a combination of nucleic acid (DNA or RNA) sequences corresponding to a product (RNA or polypeptide), specified or demarcated by the cellular system | – Modify – |
| ENCODE definition of the gene (Gerstein et al. 2007) | Gene as a union of genomic sequences encoding a coherent set of potentially overlapping functional products | – Modify – |
| Semiotic analysis of genes and genetic information (El-Hani 2009) | Genes as potential signs, actualized by semiotic process, the action of genes as signs, which is genetic information More conservative interpretation, genes still in DNA, as potential signs Less conservative interpretation, genes also treated as processes, just as genetic information | – Modify – |
| Genitor (genetic functor), Dene and Bene (Keller and Harel 2007) | Genitor (G) = (O, D, B); O, organism of a specified type; D, dene; B, bene Dene is a statement about O’s DNA; it does not say, by itself, anything about function, it is just a statement about DNA as static entity, fixed sequence Bene is a statement about O’s behavior, statement about how the organism dynamically develops, lives, behaves, etc. The genitor unifies structure (dene, D), as status aspect, and function (bene, B), as dynamic aspect, in organism O | – Drop – |
- A unit of cultural, rather than genetic, transmission. “We need a name for the new replicator, a noun that conveys the idea of a unit of cultural transmission, or a unit of imitation. ‘Mimeme’ comes from a suitable Greek root, but I want a monosyllable that sounds a bit like ‘gene’. I hope my classicist friends will forgive me if I abbreviate mimeme to meme.* If it is any consolation, it could alternatively be thought of as being related to ‘memory’, or to the French word même. It should be pronounced to rhyme with ‘cream’.” The Selfish Gene: 40th Anniversary edition (Oxford: Oxford Landmark Science, 2016; first pub. 1976) 9, Kindle Edition. ↩︎
- For a review of the book’s publication history and reception, see Soraya de Chadarevian, “The selfish gene at 30: the origin and career of a book and its title” The Royal Society Journal of the History of Science (December 2006). https://doi.org/10.1098/rsnr.2006.0162 ↩︎
- Dawkins, op. cit. ↩︎
- Ibid., p. 14. ↩︎
- Ibid., p. 3. ↩︎
- One reviewer of The Selfish Gene dismissed it, with a snort, as “a young man’s book”. Dawkins may now be to blame (no longer young) for failing to update his credences. ↩︎
- Genes encoding RNA molecules? You thought genes coded for proteins, passed the code to mRNA…. And you would be right. But genes also code for RNA molecules which are the final product and carry out functions having nothing to do with proteins. ↩︎
- Max Weber, Charisma and Disenchantment: The Vocation Lectures, Paul Reitter and Chad Wellmon eds. (New York: New York Review of Books, 2020), 22. ↩︎
- Thus discrediting the scientific endeavor in the popular Zeitgeist. Fair bit of hand wringing about this in the literature, but a side topic for the present purposes.
↩︎ - The Human Genome Project’s estimate was a surprise, as previous estimates of the number of human genes ranged from 50,000 to more than 140,000. ↩︎
- Not strictly true, but closer than not. At least in the classical model. At most 5% of your genome actually codes for proteins (some estimates are less than 2%); the rest used to be called “junk DNA.” ↩︎
- Robert Sapolsky, Behave: The Biology of Humans at our Best and Worst (New York: Penguin, 2017), 226. ↩︎
- A topic beyond this rattle. For a good introduction, see David S. Moore, The Developing Genome: An Introduction to Behavioral Epigenitics (Oxford: Oxford University Press: 2015). ↩︎
- Charbel Niño El-Hani, Genetics and Molecular Biology, 30 (2007). https://doi.org/10.1590/S1415-47572007000300001 ↩︎
- Dawkins, op. cit., p. 25. ↩︎
- L.M.N. Meyer et al., “How to Understand the Gene in the Twenty-First Century?”, Science and Education 22 (2013). https://doi.org/10.1007/s11191-011-9390-z ↩︎
- Hat tip, Sabine Hossenfelder, Existential Physics (New York: Viking 2022), xvi. ↩︎