Rapid evolution of immunoglobulin superfamily C2 domains expressed in immune system cells.

: To test the hypothesis that proteins expressed in cells of the vertebrate immune system evolve unusually rapidly, 107 orthologous immunoglobulin C2 domains were compared between human and murine rodent. The analysis showed that the rate of nonsynonymous (amino-acid-altering) nucleotide substitution in these domains was correlated with factors associated with protein structure and with breadth of tissue expression, as well as with the rate of synonymous substitution. However, when such factors were controlled for statistically, there remained a strong positive association between expression in the immune system and nonsynonymous rate, with the highest rates being seen in genes expressed in the immune system only. Certain immune system genes are known to be subject to positive selection favoring diversity at the amino acid level; most of these genes encode receptors that interact directly with foreign antigens. The observed acceleration of the rate of nonsynonymous evolution in C2 domains of immune system proteins may be explained by either (1) reduced constraint at the amino acid level on molecules interacting with immune system receptors that are themselves evolving rapidly due to positive diversifying selection or (2) positive selection favoring amino acid changes correlated with changes in the immune system receptors.