scholarly journals Diversidade na arquitetura e expressão gênica: uma análise quantitativa de Exon shuffling e splicing alternativo

2018 ◽  
Author(s):  
Fabio Passetti
Keyword(s):  
Exon Shuffling

scholarly journals Exon Shuffling Played a Decisive Role in the Evolution of the Genetic Toolkit for the Multicellular Body Plan of Metazoa

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 382
Author(s):  
Laszlo Patthy
Keyword(s):  
Transcription Factor ◽  
Decisive Role ◽  
Cell Types ◽  
Body Plan ◽  
Exon Shuffling ◽  
Body Parts ◽  
Multidomain Proteins ◽  
Cellular Phenotypes ◽  
Cell Matrix Interactions ◽  
Genetic Toolkit

Division of labor and establishment of the spatial pattern of different cell types of multicellular organisms require cell type-specific transcription factor modules that control cellular phenotypes and proteins that mediate the interactions of cells with other cells. Recent studies indicate that, although constituent protein domains of numerous components of the genetic toolkit of the multicellular body plan of Metazoa were present in the unicellular ancestor of animals, the repertoire of multidomain proteins that are indispensable for the arrangement of distinct body parts in a reproducible manner evolved only in Metazoa. We have shown that the majority of the multidomain proteins involved in cell–cell and cell–matrix interactions of Metazoa have been assembled by exon shuffling, but there is no evidence for a similar role of exon shuffling in the evolution of proteins of metazoan transcription factor modules. A possible explanation for this difference in the intracellular and intercellular toolkits is that evolution of the transcription factor modules preceded the burst of exon shuffling that led to the creation of the proteins controlling spatial patterning in Metazoa. This explanation is in harmony with the temporal-to-spatial transition hypothesis of multicellularity that proposes that cell differentiation may have predated spatial segregation of cell types in animal ancestors.

FUNCTIONAL PROPERTIES OF DELETION-MUTANTS OF TISSUE-TYPE PLASMINOGEN ACTIVATOR

1987 ◽  
Author(s):  
H Pannekok ◽  
A J Van Zonneveid ◽  
C J M de vries ◽  
M E MacDonald ◽  
H Veerman ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Structure And Function ◽  
Exon Shuffling ◽  
Tissue Type ◽  
Deletion Mutants ◽  
Lac Operon ◽  
Mutant Proteins ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
And Function

Over the past twenty-five years, genetic methods have generated a wealth of information on the regulation and the structure-function relationship of bacterial genes.These methods are based on the introduction of random mutations in a gene to alter its function. Subsequently, genetic techniques cure applied to localize the mutation, while the nature of the impairedfunction could be determined using biochemical methods. Classic examples of this approach is now considered to be the elucidation of the structure and function of genes, constituting the Escherichia coli lactose (lac) and tryptophan (trp) operons,and the detailed establishment of the structure and function of the repressor (lacl) of the lac operon. Recombinant DNA techniques and the development of appropriate expression systems have provided the means both to study structure and functionof eukaryotic (glyco-) proteins and to create defined mutations with a predestinedposition. The rationale for the construction of mutant genes should preferentiallyrely on detailed knowledge of the three-dimensional structure of the gene product.Elegant examples are the application of in vitro mutagenesis techniques to substitute amino-acid residues near the catalytic centre of subtilisin, a serine proteasefrom Bacillus species and to substituteanamino acid in the reactive site (i.e. Pi residue; methionine) of α-antitrypsin, a serine protease inhibitor. Such substitutions have resulted into mutant proteins which are less susceptible to oxidation and, in some cases, into mutant proteins with a higher specific activity than the wild-type protein.If no data are available on the ternary structure of a protein, other strategies have to be developed to construct intelligent mutants to study the relation between the structure and the function of a eukaryotic protein. At least for a number of gene families, the gene structure is thought to be created by "exon shuffling", an evolutionary recombinational process to insert an exon or a set of exons which specify an additional structural and/or functional domain into a pre-existing gene. Both the structure of the tissue-type plasminogen activator protein(t-PA) and the t-PA gene suggest that this gene has evolved as a result of exon shuffling. As put forward by Gilbert (Science 228 (1985) 823), the "acid test"to prove the validity of the exon shuffling theory is either to delete, insert or to substitute exon(s) (i.e. in the corresponding cDNA) and toassay the properties of the mutant proteins to demonstrate that an exon or a set of adjacent exons encode (s) an autonomousfunction. Indeed, by the construction of specific deletions in full-length t-PA cDNA and expression of mutant proteins intissue-culture cells, we have shown by this approach that exon 2 of thet-PA gene encodes the function required forsecretion, exon 4 encodes the "finger" domain involved in fibrin binding(presumably on undegraded fibrin) and the set of exons 8 and 9 specifies kringle 2, containing a lysine-binding sit(LBS) which interacts with carboxy-terminal lysines, generated in fibrin after plasmic digestion. Exons 10 through 14 encode the carboxy-ter-minal light chain of t-PA and harbor the catalytic centre of the molecule and represents the predominant "target site" for the fast-acting endothelial plasminogen activator inhibitor (PAI-1).As a follow-up of this genetic approach to construct deletion mutants of t-PA, we also created substitution mutants of t-PA. Different mutants were constructed to substitute cDNA encoding thelight chain of t-PA by cDNA encoding the B-chain of urokinase (u-PA), in order to demonstrate that autonomous structural and functional domains of eitherone of the separate molecules are able toexert their intrinsic properties in a different context (C.J.M. de Vries et al., this volume). The possibilities and the limitations of this approach to study the structure and the function of t-PA and of other components of the fibrinolytic process will be outlined.

Crystal structure of a protein with an artificial exon-shuffling, module M4-substituted chimera hemoglobin βα, at 2.5 Å resolution 1 1Edited by K. Nagei

1999 ◽  
Vol 287 (2) ◽  
pp. 369-382 ◽  
Author(s):  
Tsuyoshi Shirai ◽  
Masahiro Fujikake ◽  
Takashi Yamane ◽  
Kenji Inaba ◽  
Koichiro Ishimori ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Exon Shuffling

DNA ALGORITHMS BASED ON EXON SHUFFLING

2005 ◽  
Vol 38 (1) ◽  
pp. 17-21
Author(s):  
Tsuyoshi Okayama ◽  
Haruhiko Murase
Keyword(s):  
Exon Shuffling

scholarly journals A strategy of exon shuffling for making large peptide repertoires displayed on filamentous bacteriophage.

1996 ◽  
Vol 93 (15) ◽  
pp. 7761-7766 ◽  
Author(s):  
I. Fisch ◽  
R. E. Kontermann ◽  
R. Finnern ◽  
O. Hartley ◽  
A. S. Soler-Gonzalez ◽  
...  
Keyword(s):  
Exon Shuffling ◽  
Filamentous Bacteriophage ◽  
Large Peptide
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