Furthermore, the evolutionary processes involved in the emergence of cyclic h-defensins and their subsequent loss of function in humans, chimpanzees and gorillas require investigation. Loss of function is a major driving force for phenotypic change and can be advantageous, deleterious or tolerated, as explained by the hypotheses of less-is-more, less-is-less and less-is-nothing, respectively. Because of the frequent gene duplication and functional redundancy within multigene families, losing certain members is usually ‘‘tolerable’’. However,20(S)-NotoginsenosideR2 the h-defensins have significant antiviral activity that is higher than that of a-defensins and b-defensins, including anti-HIV-1 activity. The loss of functional h-defensin seems to be ‘‘deleterious’’. Therefore, the expansion of pseudogene DEFTP and the loss of functional DEFT in humans, chimpanzees and gorillas cannot be well explained by the three hypotheses noted above. The evolutionary fate of hdefensin genes may be influenced by other factors, which should be further investigated. In this study, a less-is-hitchhiking hypothesis was proposed to 20(S)-Notoginsenoside-R2 explain this process, using comparative genomics analyses. During the evolutionary process following gene duplication, due to functional divergence, the evolutionary rate of duplicated genes will initially increase and may subsequently shift with altered functional constraints or remain at the original rate with no altered functional constraints. The conserved cysteines at positions 2, 4 and 9 of the consensus motif form the tridisulfide ladder that has been proven to be important for structural stability but not for antimicrobial activity. Positions 1, 5 and 6 are mostly cationic and hydrophilic arginine residues, whereas positions 3, 7 and 8 are mostly hydrophobic residues. The side chains of arginine residues and the tridisulfide ladder are on opposite sides of the cyclic backbone plane and thus form a polarized structure. The conserved hydrophilic/hydrophobic pattern generates the cationic and amphipathic properties, which might play a major role in the membrane depolarization and permeabilization of target cells or enveloped viruses.