Modifiers, enhancers and suppressors

Question

Acetylcholinesterase (ACE) breaks down the neurotransmitter acetylcholine. ACE enzyme activity can be detected by a simple colorimetric assay in C. elegans (a nematode worm). A mutagenesis screen was carried out to find mutant worms with reduced histochemical staining for ACE enzyme activity. Mutant worms homozygous for a mutation in the gene acetylcholinesterase-1 (ace-1) have reduced levels of the enzyme. These mutant worms were assessed for defects in movement, behaviour and appearance, but were found to have very similar characteristics to wild-type worms, despite acetylcholine being an important neurotransmitter.

A modifier mutagenesis screen was carried out using the ace-1 mutant, rather than wild-type worms. In this screen, worms were identified that had uncoordinated movements. These were found to be double mutants that carried a mutation in a second gene ace-2, as well as a mutation in ace-1. These ace-1; ace-2 double mutants worms also showed a much larger reduction in acetylcholinesterase activity in the colorimetric assay, than wither ace-1 mutants or ace-2 mutants. Mutant worms, homozygous only for ace-2, also had a wild-type movement phenotype. Colorimetric assays for the enzyme also identified a reduction of acetylcholinesterase in ace-2 mutants that was similar to the reduction in ace-1 mutants.

1) What type of genetic modifier is ace-2? ANS: Enhancer

My question is, can you explain why this is an enhancer and not a suppressor? Would ace-1 be an enhancer too? I am confused.

Thank you.

Answer 1

Hi, Vivien!

In the mutant-hunting game, these terms reflect the change in phenotype. Here, we start with a defect that is too subtle for us to detect at the level of phenotype (normal in behavior, movement, appearance) despite having lowered enzyme levels. So the the researcher is thinking "why is nothing wrong? Perhaps some second gene is helping; I will use this strain and look for second defects that DO show something wrong". In other words, they are looking to ENHANCE the existing defect (which is so minor, it is not noticeably defective). So we took a minor/invisible problem and ENHANCED it so that we got uncoordinated worms.

A SUPPRESSOR takes an existing defect and makes it BETTER. So if we had uncoordinated works and looked for mutations that made them LESS uncoordinated (= more coordinated) these would be suppressors; they SUPPRESS the problem.

It is quite LIKELY that ace2 defects are no or negligible effects on their own, and that adding an ace1 defect would ENHANCE this defect. Note that there is an important idea here of 'suppressor or enhancer OF WHAT'. So (at least some) ace2 mutants are KNOWN to be enhancers of ace1 mutations. It is reasonable to suppose that ace1 mutations enhance ace2, but this would depend on the phenotype of ace2 mutants on their own and, of course, an actual experiment!