scholarly journals Concerted evolution of human amylase genes.

1988 ◽  
Vol 8 (3) ◽  
pp. 1197-1205 ◽  
Author(s):  
D L Gumucio ◽  
K Wiebauer ◽  
R M Caldwell ◽  
L C Samuelson ◽  
M H Meisler

Cosmid clones containing 250 kilobases of genomic DNA from the human amylase gene cluster have been isolated. These clones contain seven distinct amylase genes which appear to comprise the complete multigene family. By sequence comparison with the cDNAs, we have identified two pancreatic amylase genes and three salivary amylase genes. Two truncated pseudogenes were also recovered. Intergenic distances of 17 to 22 kilobases separate the amylase gene copies. Within the past 10 million years, duplications, gene conversions, and unequal crossover events have resulted in a very high level of sequence similarity among human amylase gene copies. To identify sequence elements involved in tissue-specific expression and hormonal regulation, the promoter regions of the human amylase genes were sequenced and compared with those of the corresponding mouse genes. The promoters of the human and mouse pancreatic amylase genes are highly homologous between nucleotide -160 and the cap site. Two sequence elements thought to influence pancreas-specific expression of the rodent genes are present in the human genes. In contrast, similarity in the 5' flanking sequences of the salivary amylase genes is limited to several short sequence elements whose positions and orientations differ in the two species. Some of these sequence elements are also associated with other parotid-specific genes and may be involved in their tissue-specific expression. A glucocorticoid response element and a general enhancer element are closely associated in several of the amylase promoters.

1988 ◽  
Vol 8 (3) ◽  
pp. 1197-1205
Author(s):  
D L Gumucio ◽  
K Wiebauer ◽  
R M Caldwell ◽  
L C Samuelson ◽  
M H Meisler

Cosmid clones containing 250 kilobases of genomic DNA from the human amylase gene cluster have been isolated. These clones contain seven distinct amylase genes which appear to comprise the complete multigene family. By sequence comparison with the cDNAs, we have identified two pancreatic amylase genes and three salivary amylase genes. Two truncated pseudogenes were also recovered. Intergenic distances of 17 to 22 kilobases separate the amylase gene copies. Within the past 10 million years, duplications, gene conversions, and unequal crossover events have resulted in a very high level of sequence similarity among human amylase gene copies. To identify sequence elements involved in tissue-specific expression and hormonal regulation, the promoter regions of the human amylase genes were sequenced and compared with those of the corresponding mouse genes. The promoters of the human and mouse pancreatic amylase genes are highly homologous between nucleotide -160 and the cap site. Two sequence elements thought to influence pancreas-specific expression of the rodent genes are present in the human genes. In contrast, similarity in the 5' flanking sequences of the salivary amylase genes is limited to several short sequence elements whose positions and orientations differ in the two species. Some of these sequence elements are also associated with other parotid-specific genes and may be involved in their tissue-specific expression. A glucocorticoid response element and a general enhancer element are closely associated in several of the amylase promoters.


1993 ◽  
Vol 4 (3) ◽  
pp. 503-509 ◽  
Author(s):  
Miriam H. Meisler ◽  
Chao-Nan Ting

Analysis of the structures of the human amylase genes has demonstrated that this multigene family contains at least five tandem gene copies, closely related in sequence but with distinct tissue specific expression. The structures of the genes demonstrate that the human salivary amylase gene was derived from a preexisting pancreatic amylase gene. Insertion of a retrovirus upstream of the amylase gene is responsible for the alteration in tissue specificity. A parotid specific enhancer has been identified within the retrovirus by expression studies in transgenic mice. The independent origin of salivary amylase in rodents and primates suggests that there has been strong evolutionary selection for amylase in saliva. The amylase genes demonstrate a novel mechanism for evolution of new patterns of tissue specific gene expression.


1992 ◽  
Vol 6 (8) ◽  
pp. 1457-1465 ◽  
Author(s):  
C N Ting ◽  
M P Rosenberg ◽  
C M Snow ◽  
L C Samuelson ◽  
M H Meisler

1980 ◽  
Vol 142 (1) ◽  
pp. 93-116 ◽  
Author(s):  
Ueli Schibler ◽  
Mario Tosi ◽  
Anne-Cécile Pittet ◽  
Lucia Fabiani ◽  
Peter K. Wellauer

Author(s):  
Richard A. Young ◽  
Peter K. Wellauer ◽  
Otto Hagenbuchle ◽  
Mario Tosi ◽  
Ueli Schibler

1987 ◽  
Vol 7 (1) ◽  
pp. 326-334
Author(s):  
L Osborn ◽  
M P Rosenberg ◽  
S A Keller ◽  
M H Meisler

The regulatory properties of mouse pancreatic amylase genes include exclusive expression in the acinar cells of the pancreas and dependence on insulin and glucocorticoids for maximal expression. We have characterized a murine pancreatic amylase gene, Amy-2.2y, whose promoter sequence is 30% divergent from those of previously sequenced amylase genes. To localize sequences required for tissue-specific and hormone-dependent activation, we established two lines of transgenic mice. The first line contained a single copy of the complete Amy-2.2y gene as well as 9 kilobases of 5'-flanking sequence and 5 kilobases of 3'-flanking sequence. The second line carried a minigene which included 208 base pairs of 5'-flanking sequence and 300 base pairs of 3'-flanking sequence. In both lines the transgene was expressed at high levels exclusively in the pancreas. Both constructs were dependent on insulin and induced by dexamethasone. Thus, the transferred genes contained the sequences required for tissue-specific and hormonally regulated expression.


Heredity ◽  
1996 ◽  
Vol 76 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Jean-Luc da Lage ◽  
Albert Klarenberg ◽  
Marie-Louise Cariou

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