From Electron to Retrotransposon: “-on” the Origin of a Common Suffix in Molecular Biology

Over the last year or so, I have become increasingly interested in understanding the origin of major concepts in genetics and molecular biology. This is driven by several motivating factors, primarily to cure my ignorance/satisfy my curiosity but also to be able to answer student queries more authoritatively and unearth unsolved questions in biology. One of the more interesting stories I have stumbled across relates to why so many terms in molecular biology (e.g. codon, replicon, exon, intron, transposon, etc.) end with the suffix “-on”? While nowhere as pervasive the “-ome” suffix that has contaminated biological parlance of late,  the suffix “-on” has clearly left its mark in some of the most frequently used terms the lexicon of molecular biology.

According to Brenner (1996) [1], the common use of the suffix “-on” in molecular biological terms can be traced to Seymour Benzer’s dissection of the fine structure of the rII locus in bacteriophage T4, which overturned the classical idea that a gene is an indivisible unit:

To mark this new view of the gene, Seymour invented new terms for the now different units of mutation, recombination and function. As he was a physicist, he modelled his terms on those of physics and just as electrons, protons and neutrons replaced the once indivisible atom, so genes came to be composed of mutons, recons and cistrons. The the unit of function, the cistron was based on the cis–trans complementation test, of which only the trans part is usually done…Of these terms, only cistron came to be widely used. It is conjectured that the other two, the muton and the recon, disappeared because Seymour failed to follow the first rule for inventing new words, which is to check what they may mean in other languages…Seymour’s pioneering invention of units was followed by a spate of other new names not all of which will survive. One that seems to have taken root is codon, which I invented in 1957; and the terms intron and exon, coined by Walter Gilbert, are certain to survive as well. Operon is moot; it is still frequently used in prokaryotic genetics but as the weight of research shifts to eukaryotes, which do not have such units of regulation, it may be lost. Replicon, invented by Francis Jacob and myself in 1962, seems also to have survived, despite the fact that we paid insufficient attention to how it sounded in other languages.

Thus, the fact that many molecular biological terms end in “-on” (initiated by Benzer) owes its origin to patterns of nomenclature in chemistry/nuclear physics (which itself began with Stoney’s proposal of the term electron in 1894) and the desire to identify “fundamental units” of biological structure and function.

While Brenner’s commentary provides a crucial first-hand account to understand the origin of these terms, it does not provide any primary references concerning the coining of these terms. So I’ve spent some time digging out the original usage for a number of more common molecular biology “-ons”, which I thought many be of use or interest to others.

The terms reconmuton and cistron were defined by Benzer (1957) [2] as follows:

  • Recon: “The unit of recombination will be defined as the smallest element in the one-dimensional array that is interchangeable (but not divisible) by genetic recombination. One such element will be referred to as a “recon.””
  • Muton: “The unit of mutation, the “muton” will be defined as the smallest element that, when altered, can give rise to a mutant form of the organism.”
  • Cistron: “A unit of function can be defined genetically, independent of biochemical information, by means of the elegant cistrans comparison devised by [Ed] Lewis…Such a map segment, corresponding to a function which is unitary as defined by the cistrans test applied to the heterocaryon, will be defined as a cistron.”

I have not been able to find a definitive first reference that defines the term codon the fundamental unit of the genetic code. According to Brenner (1996) [1] and US National Library of Medicine’s Profiles in Science webpage on Marshall Nirenberg [2], the term codon was introduced by Brenner in 1957 “to describe the fundamental units engaged in protein synthesis, even though the units had yet to be fully determined. Francis Crick popularized the term in 1959. After 1962, Nirenberg began to use “codon” to characterize the three-letter RNA code words” [3].

The term operon was introduced by Jacob et al. (1960) [4] and defined as follows (italics theirs):

  • Operon: “Celle-ci comprendrait des unités d’expression coordonée (opérons) constituées par un opérateur et le group de gènes de structure coodoneés par lui.”

The term replicon was introduced by Jacob and Brenner (1963) [4] and defined as follows (italics theirs):

  • Replicon: “Il est donc clair qu’un chromosome (de bactérie ou de phage) ou un épisome constitue une unité de réplication indépendante ou réplicon, dont la reproduction est régie par la présence et l’activité de certain déterminants qu’il porte. Les caractères des réplicons exigent qu’ils déterminent des systèmes spécifique gouvernant leur propre réplication.”

Near and dear to my heart is the term transposon, which was first introduced by Hedges and Jacob (1974) [7] (italics theirs):

  • Transposon: “We designate DNA sequences with transposition potential as transposons (units of transposition)”

The very commonly used terms intron and exon were defined by Gilbert (1978) [6] as follows:

  • Intron & Exon: “The notion of the cistron, the genetic unit of function that one thought to correspond to a polypeptide chain, must be replaced by that of a transcription unit containing regions which will be lost from the mature messenger – which I suggest we call introns (for intragenic regions) – alternating with regions which will be expressed – exons.”

And finally, Boeke et al. (1985) [8] defined the term retrotransposon in the following passage (italics theirs):

  • Retrotransposon: “These observations, together with the finding that introns are spliced out of the Ty upon transposition, suggest that reverse transcription is a step in the transposition of Ty elements…We therefore propose the term retrotransposon  for Ty and related elements.”

So there you have it, from electron to retrotransposon in just a few steps. I’ve left out some lesser used terms with this suffix for the moment (e.g. regulon, stimulon, modulon), so as not to let this post go -on and -on. If anyone has any major terms to add here or corrections to my reading of the tea leaves, please let me know in the comments below.

[1] Brenner, S. (1995) “Loose end: Molecular biology by numbers… one.” Current Biology 5(8): 964.
[2] Benzer, S. (1957) “The Elementary Units of Heredity.” in Symposium on the Chemical Basis of Heredity p. 70–93.  Johns Hopkins University Press
[4] Jacob, F., et al. (1960) “L’opéron: groupe de gènes à expression coordonnée par un opérateur.” C.R. Acad. Sci. Paris 250: 1727-1729.
[5] Jacob, F., and S. Brenner. (1963) “Sur la regulation de la synthese du DNA chez les bacteries: l’hypothese du replicon.” C. R. Acad. Sci 246: 298-300.
[6] Gilbert, W. (1978) “Why genes in pieces?.” Nature 271(5645): 501.
[7] Hedges, R. W., and A. E. Jacob. (1974) “Transposition of ampicillin resistance from RP4 to other replicons.” Molecular and General Genetics MGG 132(1): 31-40.
[8] Boeke, J.D., et al. (1985) “Ty elements transpose through an RNA intermediate.” Cell 40(3): 491.
Jim Shapiro (University of Chicago) gave very helpful pointers to possible places where the term “transposon” might have originally have been introduced.