Promoter shuffling has occurred during the evolution of the vertebrate growth hormone gene

Comparative studies of vertebrate gene promoter regions seldom detect gross rearrangements ('promoter shuffling' since such analyses usually employ re latively similar DNA sequences. Conversely, attempts to compare evolutionar ily more divergent promoter sequences have been largely unsuccessful owing to the inability of conventional alignment procedures to deal with gross re arrangements. These limitations have been circumvented in the present study by using the novel technique of complexity analysis to identify modular co mponents ('blocks') in the growth hormone (GH) gene promoter sequences of s ome 22 vertebrate species, From salmon to human. Significant rearrangement of blocks was found to have occurred, indicating that they have evolved as independent units. Some blocks appear to be ubiquitous, whereas others are restricted to a specific taxon. Considerable variation between orthologous GH gene promoters was apparent in terms of block length, copy number and re lative location. It may be inferred that a wide variety of different mutati onal mechanisms have operated upon the GH gene promoter over evolutionary t ime. These include gross changes such as deletion, duplication, amplificati on, elongation, contraction, transposition, inversion and fusion, as well a s the slow, steady accumulation of single base-pair substitutions. Thus the patchwork structure of the modular GH promoter region, and those of its pa ralogous GH2 and prolactin (PRL) counterparts, have continually been shuffl ed into new combinations through the rearrangement of pre-existing blocks. Although some of these changes may have had no influence on promoter functi on, others could have served to alter either the level of gene expression o r the responsiveness of the promoter to external stimuli. (C) 2000 Elsevier Science B.V. All rights reserved.