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The ₂-Microglobulin Locus of Rainbow Trout (Oncorhynchus mykiss) Contains Three Polymorphic Genes¹

Departments of Structural Biology, and Microbiology and Immunology, Stanford University, Stanford, CA 94305

₂-microglobulin (₂m) associates with MHC and related class I H chains to form cell surface glycoproteins that mediate a variety of functions in defense. In humans, monomorphism of a single ₂m gene contrasts with the diversity and polymorphism of the class I H chain genes, and a similar picture was seen in almost all other species examined. In this regard, rainbow trout (Oncorhynchus mykiss) appeared unusual: trout ₂m genes gave a complicated and polymorphic pattern in Southern blots, and a minimum of 10 different mRNA encoding two distinct types of ₂m were expressed by a single fish. Characterization of genomic clones from the same fish now shows that the rainbow trout ₂m locus consists of two expressed genes and one partial gene that are closely linked. Four copies of the locus were identified and allelic variants of each gene defined, largely through comparison of the noncoding regions. A dramatic variation in the lengths of introns is caused by variable repetitive elements and accounts for the complex pattern seen in Southern blots. By comparison to noncoding sequences, the coding regions are conserved but the three loci differ within a cluster of codons that encode residues of ₂m that do not interact with class I H chains. Additional diversity in the trout ₂m genes appears to be due to somatic mutation that might be facilitated by the abundance of repetitive DNA elements within the 12 ₂m genes of an individual rainbow trout.