Our studies on the divergence of kappa chain constant region genes in the rat have yielded the surprising findings that: 1) coding regions are diverging more rapidly than noncoding regions among these closely related genes; and 2) replacement sites are diverging more rapidly than silent sites. The patterns seen suggest that noncoding nucleotide sequences have hitherto unknown functions, and that CK domains also have important, but unknown, physiological functions. We propose to extend our studies to the lambda chain system of the rat. We will use mouse cDNA probes to isolate genomic rat sequences containing the lambda chain genes, and by genomic restriction mapping as well as nucleotide sequencing, determine the number, organization and structure of these genes. We will also prepare monoclonal antibodies to rat lambda chains, and use these to study the level and genetics of lambda chain expression in rats (for which no known genetic marker currently exists and about which very little is known). Comparing these genes to each other and to those of the mouse will establish to what extent the forces we have seen operating in the CK system are also operating in the lambda gene system, and to what degree the number and organization of rat lambda chain genes differ from their known mouse and human counterparts. We will also extend considerably our knowledge of rat immunogenetics, producing anti-lambda reagents not currently available, and potentially identify genetic markers of these proteins. The results will be important for our understanding of the relationship between structure and function both of the genes and their protein products.
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