Several gene families of the immunoglobulin superfamily (''immunoglobulin mediated immune response,'' P = 1.1610 27 ) show particularly strong enrichments for PSGs. For example, five of the six SIGLEC genes included in our analysis are under positive selection (see [34] ). A detailed examination of one immunoglobulin gene for which structural information was available-a cellsurface receptor for hepatitis A and other viruses called HAVCR1 (LRT P = 6.9610 29 )-revealed several sites under positive selection in its N-terminal V-like immunoglobulin (IgV) domain. Three of these sites correspond to regions of the protein believed to play critical roles in binding to viruses or in regulating the immune function of the gene (Figure 3 ). In addition to its role in viral defense, HAVCR1 is a key player in the hygiene hypothesis explaining the increase in allergies and asthma [35] . It also interacts with IgA (CD79A; P = 5.4610 29 ), whose deficiency is associated with increased susceptibility to autoimmune and allergic diseases [36] .