Differential Masking of Natural Genetic Variation by miR-9a inDrosophila

Abstract

Genetic variation is prevalent among individuals of the same species and yet the potential effects of genetic variation on developmental outcomes are frequently suppressed. Understanding the mechanisms that are responsible for this suppression is an important goal. Previously, we found that the microRNA miR-9a mitigates the impact of natural genetic variants that promote the development of scutellar bristles in adult Drosophila. Here we find that miR-9a does not affect the impact of genetic variants that inhibit the development of scutellar bristles. We show this using both directional and stabilizing selection in the laboratory. This specificity of action suggests that miR-9a does not interact with all functional classes of developmental genetic variants affecting sensory organ development. We also investigate the impact of miR-9a on a fitness trait, which is adult viability. At elevated physiological temperatures, miR-9a contributes to viability through masking genetic variants that hinder adult viability. We conclude that miR-9a activity in different developmental networks contributes to suppression of natural variants from perturbing development. KEYWORDS Drosophila; miRNA; heritability; sensory organs; development O RGANISMS are subject to conditions of genetic variation, and yet their morphological development is often robust to such challenges. Hence, developmental outcomes are rendered uniform even in the face of variable conditions of existence. The relationship between this developmental robustness and phenotypic variation in natural populations has long been remarked upon, and Waddington (1942) coined the word canalization to describe the process. As development becomes more robust, less phenotypic variation is observed among individuals in a population (Scharloo 1991;de Visser et al. 2003;Siegal and Leu 2014). This has implications not only for the relationship between genotype and phenotype, but also for evolution (Gibson and Wagner 2000;Gibson and Dworkin 2004;Wagner 2012). In one sense, robustness inhibits evolvability since it suppresses the phenotypic variation that selection acts upon. However, when a phenotype is robust to the effects of mutations, then genetic variation can potentially accumulate in a neutral state. This might permit a broad set of connected genotypes to express the same phenotype (Wagner 2012). Later, if canalization is impaired, the effects of the previously cryptic genetic variation are revealed as phenotypic variability. These can be subject to selection, thus enhancing evolvability.Morphological variation is a consequence of variable development between individuals. Development, in turn, is the complex outcome of dynamic interactions between regulatory molecules. Developmental dynamics have been successfully simulated by biochemical reaction network models, which vary in size, topology, and circuit composition and depend upon the specific developmental process, tissue type, and species (Kitano 2004;Stathopoulos and Levine 2005;Wunderlich and DePace 2011). Studie...

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