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(In this question, I'm only considering the molecular-biology notion of a gene, not the older Mendelian notion.)

Wikipedia defines a "gene" as "a sequence of nucleotides in DNA that is transcribed to produce a functional RNA", and an "allele" as "a variation of the same sequence of nucleotides at the same place on a long DNA molecule". Typically, one says that different alleles can be different "versions" of the same gene.

Taken literally, these definitions imply that both a "gene" and an "allele" are fully specified by their base pair sequences. But this contradicts that notion that different alleles can be different "versions" of the same gene - which implies that the notion of a "gene" is more general than that of an allele, since different alleles can correspond to the "same" gene.

The notion of "same place" in Wikipedia's definition of an allele seems to suggest that a gene is characterized by its location within a DNA molecule. I.e. two different alleles correspond to the "same gene" if they occur at the same locus on a chromosome.

So what exactly specifies the boundaries of a single gene, i.e. what specifies which alleles correspond to that gene as opposed to a different gene?

Put another way: what is the minimal amount of information required to fully specify a gene? It can't just be a base pair sequence, because that instead seems to define an allele. Is it a particular genetic locus? Or is it defined functionally, i.e. a set of alleles are instances of the "same" gene if they all code for RNA strands that are functionally similar/equivalent? If it's the latter, then is there a precise way to define "functionally similar/equivalent", or is there there some degree of subjective convention in demarking different genes? (If one allele leads to a healthy organism and another allele leads to a nonviable organism, then those seem very functionally different - so is it meaningful to say that those alleles are variations of the "same" gene?)

Or is the resolution just the empirical fact that the functional purpose of a protein is so well-correlated with the locus of its encoding DNA that we can be imprecise about specifying whether the locus or the function defines the gene?

(I've also seen the notion of a "gene" defined purely phenotypically, as in the older Mendelian framework. But my understanding is that in reality, quite few phenotypic parameters are directly controlled by individual genes - most arise from complicated polygenetic interaction effects. So it seems that in practice, a purely phenotypic characterization can't precisely demarcate individual genes.)

Yet another way to frame this same question: is "allele" or "gene" the more primitive concept?

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    $\begingroup$ Too many questions at once. Can you focus a bit? $\endgroup$
    – alec_djinn
    Jul 10, 2023 at 11:13
  • $\begingroup$ I'm not following your reasoning. A dog is a dog. A Border Collie is a dog, as is a Poodle. And a Chihuahua, a Mastiff, and a Belgian Tervuren. Does that mean a dog isn't just and fully a dog? Does that mean more is required to define a dog? Does the fact that they are all so different mean that "dog" is an impossibly imprecise definition? If a dog is born with a heart defect causing death, was it really a dog? Or is it our quotidian way of thinking about dogs that allows us to be imprecise about what a dog is? This seems to be your logic. Please forgive me if I've misunderstood. $\endgroup$ Jul 10, 2023 at 13:17
  • $\begingroup$ @alec_djinn There is only a single distinct question here, which I framed in several different ways in order to clarify what I meant to ask. Unfortunately, it doesn't seem to have worked. $\endgroup$
    – tparker
    Jul 11, 2023 at 0:04
  • $\begingroup$ @anongoodnurse You have misunderstood. Up to a few nuances, there is a simple characterization of whether two animals are the same species: whether or not they can interbreed. What is the corresponding equivalence relation that determines whether or not two alleles are the same gene? $\endgroup$
    – tparker
    Jul 11, 2023 at 0:08
  • $\begingroup$ @tparker And you have made the all-too-common mistake of assumint that, because I posit something contradicting you, that I "don't understand." I understand quite well, thank you. Two alleles are even more alike than two dogs. $\endgroup$ Jul 11, 2023 at 7:17

3 Answers 3

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I found a dedicated paper about the definition of what is a gene. Their short definition is:

“a gene is a discrete genomic region whose transcription is regulated by one or more promoters and distal regulatory elements and which contains the information for the synthesis of functional proteins or non-coding RNAs, related by the sharing of a portion of genetic information at the level of the ultimate products (proteins or RNAs)”

To your individual questions:

Speaking of the human genome, different sequences on the same locus are called alleles. It is thereby the locus that is most important for the definition. The phenotypic definition of genes is outdated. You cannot have different alleles on different loci. It is thought that gene duplication is an important mechanism of evolution; you have the same sequence on different loci so that they can evolve without functional pressure, but those are then considered different genes.

Example of paralogs, genes that are related through duplication

The genes encoding myoglobin and hemoglobin are considered to be ancient paralogs. Similarly, the four known classes of hemoglobins (hemoglobin A, hemoglobin A2, hemoglobin B, and hemoglobin F) are paralogs of each other.

Although similar, paralogs are considered different genes.

Addressing comments:

There were comments asking at which similarity two sequences are considered the same gene and someone implied this is a grey-zone and analyzed with computational tools.

Here topics were mixed up! What is done computationally is the evaluation of the probability that two genes are homologous. Even with 100% sequences identity, two genes of different species or at different loci within the human genome would not be considered to be „the same gene“. These would be called homologos (orthologs or paralogs).

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    $\begingroup$ I'm not a geneticist, so that must be taken into account in this comment. Reading from the National Human Genome Research Institute website, the gene seems to be the important thing, the locus is simply like a home address, a place where a gene is located. It would be nice to have input from a geneticist. $\endgroup$ Jul 10, 2023 at 21:45
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    $\begingroup$ @anongoodnurse: The word locus means location, nobody is arguing against that and a gene is a functional unit on the DNA. I am not saying, that the words gene and locus are interchangeable in any way, the OP presented conflicts between 3 aspects of the definition of a gene (locus, sequence, phenotype) and my answer was that locus is most important, given paralogs exist. $\endgroup$
    – KaPy3141
    Jul 11, 2023 at 18:23
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    $\begingroup$ @tparker It'll be a lot easier to learn biology if you don't constrain yourself to think of definitions as things that can be condensed to a single pithy statement. That's just not how people use terminology in the real world. $\endgroup$
    – Bryan Krause
    Jul 11, 2023 at 19:18
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    $\begingroup$ "So your proposed definition of a gene is "a set of alleles that are far more alike than different"?" That's actually a decent working definition since it also covers the case where there are multiple copies of a gene occurring in different locations. Definitions in biology are not like mathematical definitions and are frequently highly dependent on context. Sometimes it's the location that's important, sometime the general biological function, sometimes the specific sequence, and sometimes a combination of all the above. $\endgroup$ Jul 12, 2023 at 3:43
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    $\begingroup$ There are two levels of sequence you have to think about: the DNA sequence and the amino acid sequence. Two DNA sequences may differ quite a bit and still produce the same protein, which moves the debate to when are two proteins the same. There are a whole bunch of computational and experimental tools for quantifying how different two DNA sequences or protein configurations are. And people do argue violently over where to draw the line sometimes. $\endgroup$ Jul 12, 2023 at 3:51
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Folks were identifying genes for 75 years before we understood the role of DNA in heredity. Originally genes were defined as the unit of heredity from back when Mendel posited that the mechanism of inheritance was pairs of indivisible particles, each pair acting in combination to control one heritable trait.

In this question, I'm only considering the molecular-biology notion of a gene, not the older Mendelian notion.

That's where it begins to get confusing. It's not like we discovered DNA and then went back and re-worked all of our thinking about genetics to be in terms of DNA sequences rather than Mendel's abstract gene. People still do a huge amount of classical genetics: looking for interesting traits that breed true. They may eventually start looking for the underlying DNA sequence responsible for the trait, but that can still come very late in the game. That means people still often use the term 'gene' in the purely Mendelian sense: the unit of control for a heritable trait.

Of course the discovery of the role of DNA changed things. At the crudest level the model went from

One gene determines one heritable trait

to

One gene determines one protein

As the model became richer and we became aware of things like alternative splicing and lncRNA that was modified to

One gene determines (at least) one protein or one non-protein-coding RNA that has a structural, regulatory, or catalytic function.

Part of your difficulty may be that you aren't appreciating how subtle and complex simple concepts like "the same" or "similar" are when applied to biology. Two proteins or two DNA sequences may be considered "the same" without being amino acid for amino acid or base for base identical. It usually means "indistinguishable for the context in question". If we talk about a "gene for hair pigmentation", we care that the protein generated by the gene controls the color of the animal's hair, but we don't necessarily care whether the hair comes out as blonde or brunette. At other times that subtle difference is exactly what interests us, and we'll talk about the blonde allele or the brunette allele.

You can find plenty of formal definitions for the gene in references and text-books. However in actual usages people are pretty careless about what they call a gene.

My own take is that a real definition of the 'gene' is multi-level:

A gene is the unit of control of heredity which is implemented as a sequence of DNA bases which directs the synthesis of a particular protein which has a particular biological function. Said sequence is typically located at one or more specific locations in the host organism. In actual usage, people may use the word 'gene' when referring to a structure at any level of the definition without regard to the properties of the other levels.

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There are other good answers already, so I'll give an overview of the ways genes are used.

  • Biology paper gene: string of DNA that encodes for a some unit, often a protein, with some function
  • High school biology classroom gene: the above definition, but also any monogenic variation which gives rise to a phenotypic change (used as synonymous with allele or SNP)
  • Laymen gene: any hereditary factor, including overall polygenic predisposition, to some phenotype. This would probably be in "using the word incorrectly" territory.
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