The avoidance response to repellent odorants in Drosophila melanogaster, a
response essential for survival, provides an advantageous model for studies
on the genetic architecture of behavior. Transposon tagging in a highly in
bred strain of flies in combination with a rapid and simple statistical beh
avioral assay enables the identification of not only large phenotypic effec
ts, but also small aberrations from wild-type avoidance behavior. The recen
t completion of the sequence of the Drosophila genome facilitates the molec
ular characterization of transposon-tagged genes and correlation between ge
ne expression and behavior in smell-Impaired (smi) mutant lines. Quantitati
ve genetic analyses of a collection of smi lines in a coisogenic background
revealed an extensive network of epistatic interactions among genes that s
hape the olfactory avoidance response. The identification and functional ch
aracterization of proteins encoded by smi genes that form part of the olfac
tory subgenome and correlation of polymorphisms in these genes with variati
on in odor-guided behavior in natural populations will advance our understa
nding of the genetic architecture of chemosensory behavior.