Genomic organization of the rat α 2u -globulin gene cluster

Abstract

The alpha 2u-globulin are a group of similar proteins, belonging to the lipocalin superfamily of proteins, that are synthesized in a subset of secretory tissues in rats. The many alpha 2u-globulin isoforms are encoded by a multigene family that exhibits extensive homology. Despite a high degree of sequence identity, individual family members show diverse expression patterns involving complex hormonal, tissue-specific, and developmental regulation. Analysis suggests that there are approximately 20 alpha 2u-globulin genes in the rat genome. We have used fluorescence in situ hybridization (FISH) to show that the alpha 2u-globulin genes are clustered at a single site on rat Chromosome (Chr) 5 (5q22-24). Southern blots of rat genomic DNA separated by pulsed field gel electrophoresis indicated that the alpha 2u-globulin genes are contained on two NruI fragments with a total size of 880 kbp. Analysis of three P1 clones containing alpha 2u-globulin genes indicated that the alpha 2u-globulin genes are tandemly arranged in a head-to-tail fashion. The organization of the alpha 2u-globulin genes in the rat as a tandem array of single genes differs from the homologous major urinary protein genes in the mouse, which are organized as tandem arrays of divergently oriented gene pairs. The structure of these gene clusters may have consequences for the proposed function, as a pheromone transporter, for the protein products encoded by these genes.

Species Specificity in Major Urinary Proteins by Parallel Evolution

“…The rat α 2u -globulins are encoded by an estimated 20 genes clustered on chromosome 5, as determined by Southern blot and fluorescence in situ hybridization [31], [37]. Like the mouse Mup genes, these rat genes are under multi-hormone regulation, are transcribed in the adult male liver and robustly expressed in urine, but are absent or barely detectable in the female and juvenile liver [28], [38].…”

Recent Segmental Duplications in the Working Draft Assembly of the Brown Norway Rat

“…1) may be an underestimate. The fact that the ␣-2-globulin cluster shows only five duplicated genes as opposed to the estimated 15-20 copies (McFadyen et al 1999;McFadyen and Locke 2000) may be a consequence of such an effect. Although many of the expected rat gene duplications and highly homologous gene families (i.e., carboxylesterases, ␣-2-globulin, cytochrome P450 genes, serine protease inhibitor, T-cell receptor, MHC genes, etc.…”

“…Although many of the expected rat gene duplications and highly homologous gene families (i.e., carboxylesterases, ␣-2-globulin, cytochrome P450 genes, serine protease inhibitor, T-cell receptor, MHC genes, etc. ; Atchison and Adesnik 1986;Pages et al 1990;Yan et al 1995;McFadyen et al 1999;Ioannidu et al 2001;Oldfield et al 2001;Rolstad et al 2001) were validated during our analysis, not all were detected. For example, the pancreatic type ribonuclease I represents a single-copy gene within most mammalian lineages that has expanded specifically within the genus Rattus (Dubois et al 2002).…”

“…Many of the rat duplication gene clusters recovered during this analysis (natural-killer cell receptor, serine protease inhibitor, carboxylesterase, cytochrome P450 gene families, etc. ; Atchison and Adesnik 1986;Pages et al 1990;Yan et al 1995;McFadyen et al 1999;Ioannidu et al 2001;Oldfield et al 2001;Rolstad et al 2001) were also detected during an analysis of "recent" segmental duplication within the mouse lineage (Cheung et al 2003b). The fact that such tandem duplications with extensive sequence identity exist within both lineages argues for active gene conversion (Atchison and Adesnik 1986) to maintain such homologous structures within each species.…”

Phylogeny and regulation of four lipocalin genes clustered in the chicken genome: evidence of a functional diversification after gene duplication

“…Another peculiarity of the lipocalin family is the organization of several genes in cluster on a given chromosome, as shown for human, rat and mouse genomes (Chan et al, 1994;McFadyen et al, 1999). In Homo sapiens, for instance, many lipocalin genes were found at bands 32-34 of chromosome 9 long arm (9q), whereas in Mus musculus two clusters were found on chromosome 2 (band B to band C1, and bands F3 to G) and on chromosome 4 (bands B to C).…”