Intragenic complementation

Turner MA et al Human argininosuccinate lyase a structural basis for intragenic complementation. Proc Natl Acad Sci U S A 1997 94 9063. 

How can one mutation be suppressed by a second mutation at a different point in the chromosome Rarely, a mutation is suppressed by a second mutation within the same gene. Such intragenic complementation sometimes occurs when a mutation leads to an amino acid replacement that disrupts the structural stability or function of a protein. Sometimes a mutation at another site involving a residue, which interacts with the first amino acid replaced, will alter the inter-... 

Fig. 2. Biochemical classification of the nia mutants, mutated domains and intragenic complementation. A collection of Nicotiana plumbaginifolia nia mutants (defective for NR apoenzyme) was tested for NR protein and activities (Cherel et al., 1990) and checked for in vivo and in vitro intragenic complementation (Pelsy Gonneau, 1991). NR protein amounts were measured by a sandwich ELISA test using as first antibody the anti-corn NR monoclonal antibody 96.9.25 (Ch6rel eta/., 1985) shown to be directed against the haem domain (M. Kavanagh, personal communication Meyer etal., 1991). The result is shown here as + or when a positive or negative ELISA test, respectively, was observed. Many class 4 mutants, most probably frameshift and deletion mutants, complement class 3 but not class 2 mutants.

Pelsy, F. Gonneau, M. (1991). Genetic and biochemical analysis of intragenic complementation events among nitrate reductase apoenzyme-deficient mutants of Nicotiana plumbaginifolia. Genetics 127, 199-204. 

Heterokaryons are analogous to heterozygotes and can be used for tests of inter- or intragenic complementation. For example, if two strains have a common nutritional requirement (X), a heterokaryon between them is made on MM + X by using other nutritional requirements for balance. Subcultures may then be made to MM to test for complementation. Failure to complement is detected by a negative result, the failure of the heterokaryon to grow on MM. A more definitive result is obtained by the test of... 

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