It is important for organisms to be capable of producing a highly fit and replicable phenotype under environmental and genetic perturbation. Developmental stability is the tendency of morphological traits to resist the effect of developmental noise (Waddington 1957; Debat and David 2001; Klingenberg 2006). In theory, corrective mechanisms that buffer developmental noise and stabilize phenotypes evolve through stabilizing or fluctuating selection (Kawecki 2000). Artificial selection experiments on wing traits of Drosophila melanogaster revealed that phenotypic variance strongly increased under disruptive selection but decreased under stabilizing and fluctuating selection (Pelabon et al. 2010), thereby supporting the above theory. The processes responsible for developmental stability are largely unknown, but have been discussed extensively (Debat and David 2001; Meiklejohn and Hartl 2002; Klingenberg 2003b; Leamy and Klingenberg 2005). It has been suggested that a “molecular chaperone,” such as HSP90, which has been shown to buffer among genotype morphological variations in D. melanogaster and Arabidopsis thaliana (Rutherford and Lindquist 1998; Queitsch et al. 2002), is one possible corrective mechanism. Another possible mechanism is the architecture of genetic regulatory networks responsible for gene expression (Houchmandzadeh et al. 2002; Bergman and Siegal 2003). In fact, hubs in the gene regulatory network of yeast have been found to buffer environmental variation (Levy and Siegal 2008). These examples clearly show that there are molecular bases that buffer environmental and genetic perturbations and control phenotypic variation in organisms; however, it remains unclear whether they regulate developmental stability.
Developmental stability is commonly evaluated by examining fluctuating asymmetry (FA)—random deviations from perfect bilateral symmetry (Moller and Thornhill 1997; Milton et al. 2003; Debat et al. 2006; Kellermann et al. 2007). Because development can be viewed as a deterministic pathway around which there exists a random walk generated by external and internal disturbances (Emlen et al. 2006), the degree of deviation from the symmetry of otherwise perfectly symmetrical structures provides a marker of the degree of developmental stability. To examine whether FA of morphological traits is heritable, FA heritability has been estimated in a number of studies (Van Valen 1962; Palmer and Strobeck 1986; Moller and Thornhill 1997; Whitlock and Fowler 1997; Gangestad and Thornhill 1999; Fuller and Houle 2006). Some studies have found statistically significant additive genetic variations of FA (Scheiner et al. 1991); however, the general conclusion of those studies was that the heritability of FA is very low. Other than heritability estimation, molecular mechanisms controlling FA of morphological traits have been investigated in only a few studies until date. The effect of an HSP90 inhibitor, geldanamycin, and several mutation alleles of Hsp90 on FA of morphological traits has also been examined (Milton et al. 2003; Debat et al. 2006). In most experimental settings, the reduction of HSP90 activity did not affect FA, and Debat et al. (2006) concluded that although Hsp90 contributed to the buffering of phenotypic variation, it was not controlling the variation. Another well-studied stress protein gene, Hsp70 was examined for its effect on FA using two deficiency strains, but no significant effect was detected (Takahashi et al. 2011a). Recently, however, Takahashi et al. (2010) found that the suppression of the expression of three small Hsp genes—Hsp22, Hsp67Ba, and Hsp67Bc—resulted in increased FA of morphological traits, suggesting their involvement in stabilizing developmental processes. Other than Hsp genes, Scalloped wings (Scl) is suggested to interact with Rop-1 and affect asymmetry of bristle traits in an Australian sheep blowfly, Lucilia cuprina (Batterham et al. 1996; Davies et al. 1996). Until date, no other specific gene has been suggested to contribute to developmental stability; however, Breuker et al. (2006) showed that deficiencies in the genomic regions of D. melanogaster could potentially affect FA of morphological traits, thus suggesting the existence of a specific genetic architecture to control FA. Unfortunately, they assessed the effect of genetic factors on FA based on among-deficiency strains variation using 115 deficiency lines, but they did not evaluate the statistical significance of the each deficiency effect by comparing FA scores of each deficiency and the control. Using well-designed experiments, locating genomic regions responsible for FA would shed light on how FA and developmental stability are regulated in organisms.
In this study, we (1) mapped genomic regions that had effects on the mean and FA of morphological traits, and (2) characterized the trait specificity of these regions. Because FA of morphological traits is most likely polygenic and sensitive to environmental perturbations (Leung et al. 2000), genetic background and environmental conditions must be strictly controlled. A collection of isogenic deficiency strains established by the DrosDel Project (Ryder et al. 2004; Ryder et al. 2007) is an ideal tool for genome-wide deficiency mapping of a polygenic trait such as FA. We screened 435 deficiencies that covered approximately 64.9% of the entire genome region of D. melanogaster to map the region having significant effects on FA of morphological traits. As a result, we found that 406 deficiencies significantly affected the mean of morphological traits, and 92 deficiencies increased FA. These results suggest that several genomic regions have the potential to affect developmental stability. They also suggest the possibility of the existence of trait-specific and trait-nonspecific mechanisms for stabilizing developmental processes. These new findings would provide new insights into the understanding of the genetic architecture underlying developmental stability.