The shading of the rectangle represents the degree that TRIM5 will limit infection of HIV-1 (darker color means TRIM5 decreases HIV-1 infection more) and the X-axis indicates time in millions of years from the present. Each dotted line represents the reconstruction of TRIM5 as it likely existed at a node of a phylogenetic tree indicating a common ancestor of humans with chimpanzees, gorillas, orangutans, gibbons, and Old World monkeys (rhesus). Original data is found in [30] and shows that the antiviral gene TRIM5 restricted HIV-1 better at points in evolution earlier than the chimp–human common ancestor than it does after that. On the right shows an amino acid sequence of a region of TRIM5 containing amino acids that confer resistance or susceptibility to HIV-1 with the amino acids that are under the strongest positive selection in red [14]. Changes in this region cause a gain of restriction to some viruses, while causing a loss to others [33],[45]–[47]. The R332 amino acid, which represents the single largest determinant of loss of resistance to HIV-1 [48],[49], was fixed before the chimp–human common ancestor, but positive selection has continued in TRIM5 along the human lineage beyond this point.