The hallmark of immunoglobulin gene families is diversity. Thus when we study the evolution of immunoglobulin genes we are, in essence, examining the process by which these genes have acquired their diversity. At present, there are very few comparative studies which allow us to assess the evolution of immunoglobulin gene families. It has been suggested that multigene families such as immunoglobulin gene families may evolve through processes such as gene conversion and unequal crossing over. Our results have shown that gene conversion is used during the evolution of the T15 VH gene family and further suggest that this family may have experienced unequal crossing over during its evolution throughout the genus Mus. In the proposed research, we will extend our studies on the evolution of vH and CH genes in Mus to assess more accurately the mechanisms involved in the evolution of these genes. The study of this particular gene family may have relevance to the more general question of how informational multigene families evolve, we plan to use the data already obtained to examine questions of gene linkage and arrangement, expansion of family size and gene expression. Lastly, we propose from observation of our data, that immunoglobulins and other proteins which are abundantly transcribed, accumulate more replacement site substitutions than other genes. This may be a reflection of the tRNA pool size and experiments testing this hypothesis are proposed. Results from the proposed experiments will provide information concerning the evolution of immunoglobulin genes in wild populations under conditions of natural selection. It is clear that to understand more fully the origins of immunoglobulin diversity, it is necessary to define the evolutionary factors that are responsible for both the number and sequence diversity found in immunoglobulin genes. This proposal reflects the experiments we propose to more fully understand the mechanisms involved in immunoglobulin gene diversity and evolution.