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A maximum-likelihood method was used to estimate nonsynonymous-to-synonymous substitution ratios between lactoferrin (LF) genes and the results suggested that the evolution of LF gene was characterized by positive selection.Five amino acid sites were identified and subjected to positive selection,among of those four sites were convergences located in the N1 domain.Evolution force analysis revealed the constant pressure may be come from genetic arms race.Previous studies had suggested that the positive charge and amphipathic antibacterial peptides of N1 domain play an important role in the anti-bacteria process.The study reported that the positive selection sites were definite correlation with antimicrobial N1 domain and we postulate that the divergence in the N1 domain of LF proteins may result from rapid mutation to adapt relate bacteria,driven by positive selection.This research also supported the host-pathogen antagonism,as previously hypothesis that some sites involved in the interactions between transferrin and bacterial iron deprived proteins.