Variations at a quantitative trait locus (QTL) affect development of behavior in lead-exposed Drosophila melanogaster

Abstract

We developed Drosophila melanogaster as a model to study correlated behavioral, neuronal and genetic effects of the neurotoxin lead, known to affect cognitive and behavioral development in children. We showed that, as in vertebrates, lead affects both synaptic development and complex behaviors (courtship, fecundity, locomotor activity) in Drosophila. By assessing differential behavioral responses to developmental lead exposure among recombinant inbred Drosophila lines (RI), derived from parental lines Oregon R and Russian 2b, we have now identified a genotype by environment interaction (GEI) for a behavioral trait affected by lead. Drosophila Activity Monitors (TriKinetics, Waltham, MA), which measure activity by counting the number of times a single fly in a small glass tube walks through an infrared beam aimed at the middle of the tube, were used to measure activity of flies, reared from eggs to 4 days of adult age on either control or lead-contaminated medium, from each of 75 RI lines. We observed a significant statistical association between the effect of lead on Average Daytime Activity (ADA) across lines and one marker locus, 30AB, on chromosome 2; we define this as a Quantitative Trait Locus (QTL) associated with behavioral effects of developmental lead exposure. When 30AB was from Russian 2b, lead significantly increased locomotor activity, whereas, when 30AB was from Oregon R, lead decreased it. 30AB contains about 125 genes among which are likely "candidate genes" for the observed lead-dependent behavioral changes. Drosophila are thus a useful, underutilized model for studying behavioral, synaptic and genetic changes following chronic exposure to lead or other neurotoxins during development.

Figure 1

Histogram of the distribution of ADA for control flies showing the variation in the behavioral trait (ADA) we used in our QTL analysis.

Figure 2

Composite Interval Mapping for the ADA Lead Index trait showing a significant QTL at cytological marker 30AB The The Y axis is in Likelihood Ratio (LR) Units; the horizontal line indicates p < 0.01 significance level. The X axis is in centiMorgans (cM), representing the genetic map for chromosomes 1, 2 and 3.

Figure 3

Distribution of roo lines as a function of ADA Lead Index (ranked from largest to smallest) for flies in which 30AB is from the Oregon R parental line (left) versus the Russian 2b line (right). Note there are many more lines in which the index is negative (and thus lead reduces activity) for Oregon R than for Russian 2b.

Figure 4

ADA is graphed for flies representing only the Oregon R and Russian 2b parental genotypes at 30AB under control (left) and leaded (right) conditions. When the 30AB marker is Russian 2b, lead significantly increases ADA. When the 30AB marker is Oregon R, lead does not have a significant effect on ADA. The genotype by lead-treatment was significant (p<0.005). (Error bars indicate standard error of the mean; * = p < 0.015).