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When Wilhelm Johannsen coined the word “gene” back in 1909 (hmmm, less than two years until the Centennial), the word was quite unambiguous – it meant “a unit of heredity”. Its material basis, while widely speculated on, was immaterial for its usefulness as a concept. It could have been tiny little Martians inside the cells, it would have been OK, as they could have been plugged into the growing body of mathematics describing the changes and properties of genes in populations. In other words, gene referred to a concept that can be mathematically and experimentally studied without a reference to any molecules or intracellular processes.

Fast-forward half a century to the discovery of DNA and subsequent discoveries of the genetic code, transcription, translation, various types of gene regulation, etc. Everyone was happy – finally, we had a material gene. We had a molecule of inheritance that we could study. And an army of thousands started studying it, announcing breakthroughs at a breath-taking pace.

The confusion about the use of the term ‘gene’, as everyone used it differently, grew over the years. The use of terminology from information theory (e.g., program, transcription, translation, algorithm) affected the way researchers thought and designed experiments, limiting for a long time all discourse on inheritance to just DNA and worse, just to the DNA sequence.

But research went on, hit the walls, and smart people found the ways around the conundrum. What the research uncovered undermined the “gene” as a unit of inheritance, and for that matter undermined DNA as the molecule of inheritance. What we have learned is that:

- there is a difference between what an organism gets from parents (a static concept of the gene) and what it does with it to properly develop, function and behave in a species-specific way (a dynamic concept of the gene)

- the DNA sequence is just one of many properties of DNA that is important for proper development, function and behavior of an organism – there are other properties of DNA, as well as other non-DNA factors that are equally important.

- a sequence of nucleotides that gets transcribed is a very poor definition of a gene, as so much happens between transcription and the generation of the final protein shape, not to mention the complexity of the question how a single protein contributes to the appearance of a phenotypic trait.

- DNA is not the only “thing” that an organism gets from the parents. There is also a DNA methylation pattern, the transcription/translation machinery of the egg cell, various molecules (RNA, proteins, steroid hormones, etc.) present in the egg cell or introduced by the sperm cell, the environment inside the egg or womb, and the external environment into which the parents deposit the progeny (including the special case of teaching/learning).

I have thought about this quite a lot over the years (see, for instance this, this, this, this and this) and more I thought about it, more I liked the ideas that Developmental Systems Theory had to offer. Last ten years of published research changed the way we think about this and changed my mind in many ways. In a way, I was right all along – it’s not just DNA that confers heredity (static concept of the gene). In other cases, I was wrong: it turned out that it is, in fact, DNA, just not its sequence, that does this or that job in running the organism (the dynamic concept of the gene).

Two of the books I have read over the years that tackled the problem in a very good way (though sometimes not going far enough for my own tastes) are Refiguring Life and The Century of the Gene by Evelyn Fox Keller, one of the most prominent thinkers about the problem right now.

Thus, I got really excited when I heard that Chris Surridge, editor of PLoS ONE, after mulling over it for a long time (philosophy of science is not supposed to be one of the topics ONE publishes papers on, at least officially and at least until now), decided to go with the reviewers’ recommendations and publish a paper by Evelyn Fox Keller and David Harel – Beyond the Gene – in which the concept of the gene is discussed. What the paper does, on top of coming up with concepts that clearly differentiate between the static and the dynamic meanings and incorporate the current understanding of the complexity of both, is propose new names for those concepts. Read it carefully – it is quite thought-provoking.

Proposing new terminology is easy. Having it accepted and used by others is far more difficult. Especially when the terms are picked very cleverly to pick up on particular mental associations, while at the same time being (probably intentionally) catchy and funny (if you read them out loud they sound like deans, beans and janitors). The straight-laced researchers will probably balk at the new words. The folks that give funny names to Drosophila genes (e.g., Sonic hedgehog or fruity…er, fruitless) will probably grok why these new proposed terms are potentially useful.

Just like their conception of gene in everyday work differs, I expect that the response to this article’s proposal will differ between a biochemist, a bioinformatics scientist, a biological anthropologist, a medical researcher and a developmental biologist, between someone who works on microbial genomes, or mammalian genetics, or compares all genomes or looks at the way viral and mammalian genomes interract, or someone who looks at evolution of genes, or population genetics, history of biology or philosophy of biology. I hope they and others chime in.

Comments

  1. #1 Blake Stacey
    November 28, 2007

    Uh-oh. “Functor” is also a term in category theory. From the PLoS ONE piece:

    Accordingly, we propose to be explicit about this conjunction, and thus introduce as our main concept, the genetic functor, or the genitor. This we define as the logical relation that says: Whenever the organism is seen to have X, it does Y. Or to use our new terms, a genitor relates a particular dene to a particular bene, stating that whenever the organism’s DNA is seen to satisfy the property expressed by the dene, it’s behavior satisfies the property expressed by the bene.

    The mathematical meaning would be preserved if denes and benes were both categories: each dene D and bene B would be (roughly speaking) a set of objects or elements with arrows from one element to another, satisfying some definitions which Mark Chu-Carroll could tell you all about.

    And, hell, is that a confusion between its and it’s I see?

  2. #2 Phil
    November 29, 2007

    The problem I’ve always had with “gene” is that sometimes it means “locus” and sometimes it means “allele.” I think those two terms are very useful, but I also understand what the authors are getting at, now that we’ve discovered epigenetics and such.

    They repeatedly refer to their new terms as “rich,” but to me the terms seem overly broad, bordering on nebulous, and thus not very useful (or any more useful than gene currently is). I can see “genetic functor” perhaps catching on, but dene and bene are just too silly to ever gain traction.

  3. #3 Colugo
    December 4, 2007

    “There is also a DNA methylation pattern, the transcription/translation machinery of the egg cell, various molecules (RNA, proteins, steroid hormones, etc.) present in the egg cell or introduced by the sperm cell”

    epigenes

    “the environment inside the egg or womb,”

    maternal factors

    “and the external environment into which the parents deposit the progeny”

    constructed niche

    “(including the special case of teaching/learning).”

    memes (behavioral and symbolic)

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