Phillips-Garcia, A. | Search bioRxiv

bioRxiv2026

Interspecific differences in second-site modifiers reshape dominance in a Mendelian trait by altering environmental plasticity

Dominance is an important and evolvable property of the genotype-phenotype map. A longstanding debate in evolutionary genetics concerns whether dominance is determined primarily by intrinsic properties of alleles at the focal locus or by modifiers elsewhere in the genome. Theoretical models show that second-site modifiers of dominance can evolve under some conditions. However, direct empirical tests of these models are rare because they require holding the focal heterozygous genotype constant while changing the rest of the genome. In the Drosophila montium species subgroup, female pigmentation is a Mendelian trait controlled by a single gene, POU domain motif 3 (pdm3), but the dominance relationships between pdm3 alleles differ among species. Using reciprocal introgressions among three closely related species, we compared females carrying the same Light/Dark pdm3 allele combinations in different homozygous or heterozygous genomic backgrounds and across different temperatures. In both species-pair comparisons, changing genomic background significantly altered the phenotype of identical pdm3 heterozygotes, demonstrating the existence of second-site modifiers of dominance. The effects of dominance modifiers depend on the particular pair of pdm3 alleles and on rearing temperature. These results show that dominance in this system is a genotype-by-genotype-by-environment trait, rather than a fixed attribute of individual alleles. The finding that second-site modifiers can alter dominance by reshaping reaction norms provides a developmental mechanism that links the evolution of dominance to phenotypic plasticity.

evolutionary biology↗

bioRxiv2025

Evolution of dominance in a Mendelian trait is linked to the evolution of environmental plasticity.

Allelic dominance and phenotypic plasticity both influence how genetic variation is expressed in phenotypes, shaping evolutionary responses to selection. In both cases, changes in genotype or environment can cause sharp, nonlinear phenotypic shifts, hinting at shared underlying features of development that may link dominance and plasticity. Here, we investigate these links using a Mendelian, female-limited color dimorphism found in many species of the Drosophila montium lineage. In most species, the Dark allele is dominant, but two species--D. jambulina and D. cf. bocqueti--have been reported to have dominant Light alleles. We show that in both Dark-dominant and Light-dominant species, the color dimorphism is linked to the same locus: the POU domain motif 3 (pdm3) transcription factor. We then demonstrate that the interspecific differences in dominance relationships between pdm3 alleles are due to changes in phenotypic plasticity. In the Dark-dominant species D. rufa and D. burlai, the Dark allele is dominant across all developmental temperatures. In contrast, in both Light-dominant species, dominance is temperature-dependent, with the Light allele becoming increasingly dominant at higher temperatures. These results suggest a mechanistic connection between the evolution of dominance and phenotypic plasticity. We propose this connection may emerge from threshold-like properties of developmental systems. Teaser textThis study reveals a direct relationship between the evolution of dominance and phenotypic plasticity in a Mendelian, female-limited color dimorphism. This trait is linked to the same transcription factor gene, pdm3, in multiple species of the Drosophila montium lineage. However in some species, the Light pdm3 allele becomes increasingly dominant at higher temperature, while in others the Dark allele is fully dominant under all conditions. Based on these results, we propose that the evolution of dominance and plasticity may be connected by threshold-like properties of developmental systems.

evolutionary biology↗