Defensins are cysteine-rich cationic peptides that function in antimicrobia
l defense in both invertebrates and vertebrates. Three main groups of anima
l defensins are known: insect defensins; mammalian alpha-defensins and vert
ebrate beta-defensins. It has been difficult to determine whether these mol
ecules are homologous or have independently evolved similar features, but o
verall the evidence favors a distant relationship. The best evidence of thi
s relationship is structural, particularly from their overall three-dimensi
onal structure and from the spacing of half-cystine residues involved in in
tra-chain disulfide bonds. Some evidence favors a closer relationship betwe
en vertebrate beta-defensins and insect defensins than between the two grou
ps of vertebrate defensins. Examination of nucleotide substitutions between
recently duplicated mammalian defensin genes shows that the rate of nonsyn
onymous (amino-acid-altering) substitution exceeds that of synonymous subst
itution in the region of the gene encoding the mature defensin. This highly
unusual pattern of nucleotide substitution is evidence that natural select
ion has acted to diversify defensins at the amino acid level. The resulting
rapid evolution explains why it is difficult to reconstruct the evolutiona
ry history of these molecules.