TRIM5 restriction of HIV-1 has decreased during evolution leading to humans.

<p>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 <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1000301#pbio.1000301-Goldschmidt1" target="_blank">[30]</a> 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 <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1000301#pbio.1000301-Hughes1" target="_blank">[14]</a>. Changes in this region cause a gain of restriction to some viruses, while causing a loss to others <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1000301#pbio.1000301-Kaiser1" target="_blank">[33]</a>,<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1000301#pbio.1000301-DiazGriffero1" target="_blank">[45]</a>–<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1000301#pbio.1000301-Song1" target="_blank">[47]</a>. The R332 amino acid, which represents the single largest determinant of loss of resistance to HIV-1 <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1000301#pbio.1000301-Stremlau1" target="_blank">[48]</a>,<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1000301#pbio.1000301-Yap1" target="_blank">[49]</a>, was fixed before the chimp–human common ancestor, but positive selection has continued in TRIM5 along the human lineage beyond this point.