The alpha(1)-microglobulin/bikunin gene: characterization in mouse and evolution

The 129Sv mouse gene coding for the alpha(1)-microglobulin/bikunin precurso r has been isolated and characterized. The 11 kb long gene contains ten exo ns, including six 5'-exons coding for alpha(1)-microglobulin and four 3'-ex ons encoding bikunin. Exon 7 also codes for the tribasic tetrapeptide RARR which connects the alpha(1)-microglobulin and bikunin parts. The sixth intr on, which separates the alpha,-microglobulin and bikunin encoding parts, wa s compared in the human, mouse and a fish (plaice) gene. The size of this i ntron varies considerably, 6.5, 3.3 and 0.1 kb in man, mouse and plaice, re spectively. In all three genes, this intron contains A/T-rich regions, and retroposon elements are found in the first two genes. This indicates that t his sixth intron is an unstable region and a hotspot for recombinational ev ents, supporting the concept that the alpha,-microglobulin and bikunin part s of this gene are assembled from two ancestral genes. Finally, the nonsyno nymous nucleotide substitution rate of the gene was determined by comparing coding sequences from ten vertebrate species. The results indicate that th e alpha,-microglobulin part of the gene has evolved faster than the bikunin part. (C) 1999 Elsevier Science B.V. All rights reserved.