Dosage‐dependent modification of position‐effect variegation in Drosophla

Abstract

Many loci in Drosophila exhibit dosage effects on single phenotypes. In the case of modifiers of position-effect variegation, increases and decreases in dosage can have opposite effects on variegating phenotypes. This is seemingly paradoxical: if each locus encodes a limiting gene product sensitive to dosage decreases, then increasing the dosage of any one should have no effect, because the others should remain limiting. An earlier model put forward to resolve this paradox suggested that dosage-dependent modifiers encode protein subunits of a macromolecular complex that is sensitive to mass action equilibrium conditions. Because chemical equilibria are dynamic, however, such hypothetical complexes will be unstable to an extent that is inconsistent with the known properties of molecules that make up chromatin. An alternative model accounts for the dosage effects in terms of interactions between structural proteins that bind at multiple linked sites. These might include indirect interactions occurring between regulatory proteins and genes for structural proteins or their protein products. The large number of direct and inverse regulatory genes which are known to exist in Drosophila could account for the apparent genetic complexity that is seen for modifiers of position-effect variegation and for other systems of phenotypic modification.

Gene balance hypothesis: Connecting issues of dosage sensitivity across biological disciplines

“…Several other laboratories noted that transcription factors, tumor suppressor genes, and components of signal transduction are dosage-sensitive (42)(43)(44)(45). This realization was consistent with the fact that many transcription factors control developmental decisions in Drosophila in a concentration-dependent manner (46)(47)(48)(49)(50)(51), and the myriad of modifiers of position effect variegation are dosage-sensitive (52). Dosage sensitivity will operate through a cascade of regulatory steps, allowing many connected genes to affect any one process (41).…”

Stable transformation of the yellow fever mosquito, Aedes aegypti , with the Hermes element from the housefly

“…The results of intercrosses performed for families 35 and 64 also were consistent with a single chromosomal insertion of the transgene. Family 35 has an interesting insertion that results in variable expression of the phenotype, reminiscent of either position-effect variegation or somatic excision of the transposon (21). Due to this effect it was not possible to determine which animals were homozygous or heterozygous for the transgene; therefore the results were evaluated based on a 3:1 ratio of colored eye͞white eye phenotypic segregation.…”

Identification of the Drosophila interband-specific protein Z4 as a DNA-binding zinc-finger protein determining chromosomal structure

“…Therefore, surprisingly, a reduction of the Z4 dose enhances the expression of w m4 , which categorizes Z4 as a haplo-suppressor of w m4 PEV. Previously, some of the haplosuppressors of PEV were shown to have a triplo-enhancer effect (see Henikoff, 1996). The influence of three copies of Z4 on w m4 PEV could be investigated with the line P[Z4myc]2A, which expresses a transgenic Z4 gene with a myc-tag (see Fig.…”