Figure 3 A) Natural ligand binding sites on human serum albumin (HSA). The serum albumins domains I to III and their subdomains (A and B) are differentially colored and depicted. Additionally, the approximate locations of the natural ligand binding sites of human albumin are highlighted. Figure adapted from⁴². B) Sites under positive selection predicted with MEME software, exemplified on the crystallographic structure of human albumin (PDB ID 1AO6).

The high percentage of overlapping residues evolving under positive selection and biological relevant cavities indicate that most of them are participating in the transport, binding and/or catalytic promiscuous activities, indicating a recent pattern of functional adaptation in the evolution of seroalbumin.