Abstract
Fluctuating asymmetry (FA), typically measured by variation in the differences between right and left sides of bilateral traits, is commonly used to assess developmental instability (DI) in populations. A previous quantitative trait locus (QTL) investigation using an F2 intercross mouse population found little evidence of individual loci affecting FA in mandible size, but an abundance of epistatic interactions between loci. Here we extend this work by testing whether these patterns replicate in an F3 population derived from the same intercross. Using a large number of molecular markers genotyped in over 1200 mice, we uncovered significant interactions between loci (QTLs) affecting FA in mandible size (and shape). Epistasis contributed roughly 20% of the variation in FASIZE and 19% of the variation in FASHAPE at the 0.0001 probability level alone, and was comparable to that previously estimated for the F2 mice, and much greater than that generated from the few single-locus QTLs affecting the mandible FA traits. The positions of the single-locus and epistatic QTLs for FA that we discovered suggested that logical candidate genes for DI are those controlling size or shape in the traits themselves, and that they may be interacting with genes for heat shock proteins.
Highlights
Fluctuating asymmetry (FA), typically measured by non-directional variation in the differences between left and right sides of bilateral traits, is a widely-used measure of developmental instability (DI).DI is generated from any of a number of internal or external stressors that perturb the normal developmental pathway of structures and result in random developmental noise [1,2,3]
We found 10 quantitative trait locus (QTL) previously mapped for centroid size (CENT) and shape (SH) in this same F3 mouse population [23] that colocalize with the FA QTLs, and have listed these in Table 4 as well
Our analysis demonstrated that the genetic basis for FA in the mandible traits is primarily epistatic, with little evidence for single-locus effects
Summary
Fluctuating asymmetry (FA), typically measured by non-directional variation in the differences between left and right sides of bilateral traits, is a widely-used measure of developmental instability (DI).DI is generated from any of a number of internal or external stressors that perturb the normal developmental pathway of structures and result in random developmental noise [1,2,3]. Results from a number of studies using a wide variety of environmental stressors (toxins, noise, parasites, radiation, etc.) have supported this expectation, it has not been universally found [6]. Even after years of investigation, the genetic basis for DI remains obscure [6]. It is still not entirely clear, for example, whether DI is even heritable since many heritability estimates made for FA in various traits have been low in magnitude and non-significant [6]. Several investigators [10,11] have argued that this is partly because FA is difficult to measure, and sample sizes and experimental designs used in many of these studies may not have been optimal. Using a selection regime with large sample sizes, Carter and Houle [12] were able to demonstrate statistical significance for estimates of the heritability of FA in Drosophila wing lengths that were less than 0.01
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