The alpha1-microglobulin/bikunin gene:: characterization in mouse and evolution

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