The Drosophila argonaute2 (ago2) gene plays a
major role in siRNA mediated RNA silencing pathways. Unlike mammalian Argonaute
proteins, the Drosophila protein has an unusual amino-terminal
domain made up largely of multiple copies of glutamine-rich repeats (GRRs). We
report here that the ago2 locus produces an alternative
transcript that encodes a putative short isoform without this amino-terminal
domain. Several ago2 mutations previously reported to be null
alleles only abolish expression of the long, GRR-containing isoform. Analysis of
drop out (dop) mutations had previously
suggested that variations in GRR copy number result in defects in RNAi and
embryonic development. However, we find that dop mutations
genetically complement transcript-null alleles of ago2 and that
ago2 alleles with variant GRR copy numbers support normal
development. In addition, we show that the assembly of the central RNAi
machinery, the RISC (RNA induced silencing complex), is unimpaired in embryos
when GRR copy number is altered. In fact, we find that GRR copy number is highly
variable in natural D. melanogaster populations as well as in
laboratory strains. Finally, while many other insects share an extensive,
glutamine-rich Ago2 amino-terminal domain, its primary sequence varies
drastically between species. Our data indicate that GRR variation does not
modulate an essential function of Ago2 and that the amino-terminal domain of
Ago2 is subject to rapid evolution.