To investigate the molecular nature and rate of spontaneous mutation in Dro
sophila melanogaster, we screened 887,000 individuals for de novo recessive
loss-of-function mutations at eight loci that affect eye color. In total,
28 mutants were found in 16 independent events (13 singletons and three clu
sters). The molecular nature of the 13 events was analyzed. Coding exons of
the locus were affected by insertions or deletions >100 nucleotides long (
6 events), short frameshift insertions or deletions (4 events), and replace
ment nucleotide substitutions (1 event). In the case of 2 mutant alleles, c
oding regions were not affected. Because similar to 70% Of spontaneous de n
ovo loss-of-function mutations in Homo sapiens are due to nucleotide substi
tutions within coding regions, insertions and deletions appear to play a mu
ch larger role in spontaneous mutation in D. melanogaster than in H. sapien
s. If so, the per nucleotide mutation rate in D. melanogaster may be lower
than in H. sapiens, even if their per locus mutation rates are similar.