Beadle and Tatum proposed the “one gene, one enzyme” hypothesis in the 1940s, and this was later modified to “one gene, one protein”, i.e. that one gene codes for one protein.

Have any exceptions to this emerged subsequently? Are there single proteins, parts of which are encoded by separate genes?

  • $\begingroup$ don't forget that one gene can can code for multiple proteins... splice variants en.wikipedia.org/wiki/Alternative_splicing $\endgroup$ – Vance L Albaugh Jul 5 '16 at 21:34
  • $\begingroup$ @VanceLAlbaugh But are there proteins that emerge from more than one gene instead of parts of one? $\endgroup$ – descheleschilder Jul 6 '16 at 2:59
  • $\begingroup$ @VanceLAlbaugh Is it possible that two adjacent genes melt together and are expressed if as they are óne gene? $\endgroup$ – descheleschilder Jul 6 '16 at 3:19
  • $\begingroup$ The short answer to your initial question is yes. There are many examples of proteins that are the result of the expression of multiple genes. Hemoglobin, immunoglobulins, microtubules made of different tubulin subunits, etc. As for the other question, that is less prevalent in eukaryotes. It is not unheard of for bacteria to express operons as a single RNA, though ribosomes usually translate individual proteins. Viruses are known to do this. HIV's genome is translated from a long RNA that contains multiple genes into a single polypeptide which is then cleaved post-translationally. $\endgroup$ – AMR Jul 6 '16 at 7:16
  • $\begingroup$ @AMR There is a single gene that codes for a polyprotein, not multiple genes. After proteolytic cleavage multiple proteins arise. This is an example of one gene, many proteins and not the vice-versa. $\endgroup$ – WYSIWYG Jul 7 '16 at 6:08

There are proteins encoded by more than one gene.

It would be a heterodimer protein of quaternary structure. One famous example would be haemaglobin, which is assembled from alpha and beta sub-units.

Also, one gene is capable of coding for multiple proteins!




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  • $\begingroup$ Though hemoglobin is not a dimer as your answer seems to imply. $\endgroup$ – canadianer May 15 '18 at 2:26
  • $\begingroup$ As I had modified the question I had to clarify the "yes" in your answer. $\endgroup$ – David May 15 '18 at 8:24
  • $\begingroup$ I'm surprised that one gene is capable of coding multiple genes, which brings to mind a question I'm gonna ask now. $\endgroup$ – descheleschilder May 16 '18 at 10:28

Generally speaking the answer would seem to be:

“No, a single polypeptide chain is encoded by a single mRNA from a single transcript of a single gene.”

Obviously if one uses the epithet, protein, for a hetero-multimer like haemoglobin, one could say yes instead.

So far, nothing new since the question was posed two years ago. But, at the risk of being shot down in flames, let me suggest two possibilities.

1. Immunoglobulins

The vast diversity of antibodies arises not from the fact that there are a vast number of immunoglobulin genes in the genome, but that there is a repertoire corresponding to different sections of each antibodody chain, the recombination of which in individual B-cells gives rise to different genes. See, for example, this section of Alberts et al. As far as the precursor cell is concerned, the mature immunoglobulin chains are the products of different genes. As far as the mature individual B cells are concerned, each chain of their gene products arise from a single recombined gene.

You pays your money and you takes your choice.

2. Metalloproteins

Let us consider the metalloprotein like urease. This enzyme, which breaks down urea to ammonia and carbon dioxide, requires Nickel to function. One can adopt the standpoint that the protein is not complete without the metal cofactor. The genetics of urease has been well studied in certain pathogentic bacteria like Helicobacter pylori, where it is part of a gene cluster. Other components of this gene cluster encode proteins required to deliver nickel ions to the inactive enzyme.

One could argue that without Nickel the protein is incomplete, so that functional urease is encoded by multiple genes of that cluster.

Depends what rules we are playing.

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There are protein complexes which are made up of multiple subunits. Whether you call that one protein or a multi-protein complex might depend on whether you have a gene-centric or protein-centric point of view.

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  • $\begingroup$ Not really. A protein is a single polypeptide chain. There are many proteins that exist (sometimes solely) as a part of multi-member complexes, but those complexes are never referred to as proteins. They're called protein complexes, even by very "protein-centric" (your phrase) biochemists. $\endgroup$ – MattDMo Jul 6 '16 at 1:03
  • $\begingroup$ Now, there have been cases where a complex was initially thought to be a single protein, and named as such, but further research showed it contained multiple subunits. But after the new knowledge is disseminated, one wouldn't keep referring to the complex as a protein. $\endgroup$ – MattDMo Jul 6 '16 at 1:06
  • $\begingroup$ @MattDMo What is meant by subunits? Doesn´t every protein contain them? $\endgroup$ – descheleschilder Jul 6 '16 at 2:40
  • $\begingroup$ @descheleschilder - ask a question as a question post, not a comment. $\endgroup$ – mgkrebbs Jul 6 '16 at 5:13
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    $\begingroup$ @MattDMo You are kidding, right? from Lehninger Principles of Biochemistry; protein: A macromolecule composed of one or more polypeptide chains, each with a characteristic sequence of amino acids linked by polypeptide bonds. quaternary structure: The three-dimensional structure of a multisubunit protein, particularly in the manner in which the subunits fit together. Hemoglobin is a protein... and its subunits come from distinctly different genes that encode the polypeptides that make up the subunits of the protein. $\endgroup$ – AMR Jul 6 '16 at 6:55

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