Toll and Toll-related proteins play an important role in antibacterial inna
te immunity in insect, plants, and mammals. We present the first comprehens
ive phylogenetic analyses of Toll-related genes from both insects and mamma
ls. Drosophila melanogaster contains Toll and a highly homologous gene, Teh
ao. The protein, Dm Tehao, comprises 795 amino acid residues and its cytopl
asmic domain shares a striking 61% identity with Dm Toll. Two Toll homologu
es were found in another dipteran of medical importance, Anopheles gambiae,
a vector for human malaria. One Toll-like gene each was identified from Ae
des aegypti and Glossina palpalis palpalis, vectors for yellow fever and tr
ypanosomiasis, respectively. Phylogenetic analyses revealed separate cluste
ring of Toll and related proteins from insects and mammals, suggesting inde
pendent evolution of the Toll family of proteins and of innate immunity in
arthropods and vertebrates. These results also provide new avenues to under
standing the function of Toll proteins in insect innate immunity against ba
cteria, fungi, and protozoans.