Consider a hypothetical population of 1000 organisms.

(a) 300 of these 1000 have a T to G substitution at a specific position 1.

(b) 200 of these 1000 have an A to T substitution at a second position 2.

(c) All of the 200 with the substitution at position 2 (b) also have the substitution at position 1 (a).

As a non-geneticist, I would call the second mutation a refinement of the first mutation. Would that seem reasonable, or is there a specific technical term for this phenomenon?

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    $\begingroup$ Can you clarify why it would be a "refinement"? Why do you suppose that there is any connection between the two mutations? Why not just a second-site mutation that occurred later in the same clone as the first mutation? I'd recommend looking into previous work tracking mutations across time, e.g. genetics.org/content/200/2/619 $\endgroup$ – Maximilian Press May 17 '20 at 18:55
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    $\begingroup$ Your question needed a little tidying up and someone had suggested some changes. I have tried to lay it out in a more concise and readable fashion. In particular I have removed the term "refinement" from the title as that really begs the question. Better, I think to describe the phenomenon and then give it your own description in the body of the question. But you are free to revert as you see fit. (But use SE's own tool console for emphasis. Whatever you did, didn't work for me.) $\endgroup$ – David May 18 '20 at 17:26
  • $\begingroup$ Yes, good point. Refinement is a bad word because it has a value to it. I don't suspect that there is any relation between the two mutations. As a mathematician I'd say that the set of organisms that have a mutation in position 2 is a strict subset of the set of organisms that have mutation in position 1, but this is also bad notation somehow. (Thanks @David for great edits). $\endgroup$ – Frederik Ravn Klausen May 18 '20 at 20:05
  • $\begingroup$ I am not a geneticist either, although a molecular biologist, so cannot be sure whether there is a term for what you describe. For my part, I would describe the results in a factual manner before considering possible explanations of the type suggested by @Dirigible. $\endgroup$ – David May 18 '20 at 20:39

The description of the second mutation depends on the nature of its relationship to the first mutation.

If the first mutation reduces fitness of the organism, and the second mutation tempers the fitness reduction, then the second mutation would be compensatory.

Compensatory mutations are common in bacteria that acquire antibiotic resistance. Consider a strain of E. coli that acquires resistance to streptomycin by mutating the rpsL gene, which encodes a 30S ribosomal protein targeted by streptomycin. In the presence of streptomycin, the rpsL mutant is obviously more fit than wild type E. coli. In the absence of streptomycin, however, ribosomal mutations lead to inefficient translation. Compensatory mutations may then arise elsewhere in rpsL or within another gene involved in the ribosomal complex, partially alleviating the fitness defect caused by the initial mutation to rpsL.

If, instead, the mutations are synonymous and otherwise unrelated in their functional potential, I would simply call those mutations coincident in the genome, though this isn't really a "technical" term. If you wish to describe the relevance of these synonymous mutations in context of the three distinct genotypes given in the question, you could say that the first T to G transversion differentiates strain X from ancestral Wild Type, and the second A to T transversion differentiates strain Y from ancestral strain X. This assumes that both of these mutations occurred once in the genetic history of this population.

  • $\begingroup$ Thanks - I am not thinking about the fitness though. What would you call it if all mutations were synonomous. $\endgroup$ – Frederik Ravn Klausen May 18 '20 at 18:58
  • $\begingroup$ @FrederikRavnKlausen, I've updated my answer. Do you have a specific organism or system in mind, or is this truly hypothetical? $\endgroup$ – acvill May 18 '20 at 19:48
  • $\begingroup$ Thanks, I have the Sars-Cov-2 in mind. Here there is a very specific strain the Wuhan reference and with respect to that one can track the mutations one after another so they actually quite accurately behave as the example above. @Dirigible $\endgroup$ – Frederik Ravn Klausen May 18 '20 at 19:58
  • $\begingroup$ @FrederikRavnKlausen, That's helpful. I'd recommend editing your question to include that information. At the moment, your question is very abstract, and reads a bit like an XY-problem. $\endgroup$ – acvill May 18 '20 at 20:29

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