Molecular evolution of transferrin: Evidence for positive selection in salmonids

Transferrins are iron-binding proteins that are involved in iron storage an d resistance to bacterial disease. Previous work has shown that nonsynonymo us-to-synonymous-site substitution ratios (d(n)/d(s) ratios) between transf errin genes from some salmonid species were significantly greater than 1.0, providing evidence for positive selection at the transferrin gene. The pur pose of the current study was to put these earlier results in a broader evo lutionary context by examining variation among 25 previously published tran sferrin sequences from fish, amphibians, and mammals. The results of the st udy show that evidence for positive selection at transferrin is limited to salmonids-d(n)/d(s) ratios estimated for nonsalmonid lineages were generall y less than 1.0. Within the salmonids, similar to 13% of the transferrin co don sites are estimated to be subject to positive selection, with an estima ted d(n)/d(s) ratio of similar to7. The three-dimensional locations of some of the selected sites were inferred by comparing these sites to homologous sites in the bovine lactoferrin crystallographic structure. The selected s ites generally fall on the outside of the molecule, within and near areas t hat are bound by transferrin-binding proteins from human pathogenic bacteri a. The physical locations of sites estimated to be subject to positive sele ction support previous speculation that competition for iron from pathogeni c bacteria could be the source of positive selection.