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Abstract:

The proopiomelanocortin gene (POMC) is expressed in the pituitary gland and the ventral hypothalamus of all jawed vertebrates, producing several bioactive peptides that function as peripheral hormones or central neuropeptides, respectively. We have recently determined that mouse and human POMC expression in the hypothalamus is conferred by the action of two 5′ distal and unrelated enhancers, nPE1 and nPE2. To investigate the evolutionary origin of the neuronal enhancer nPE2, we searched available vertebrate genome databases and determined that nPE2 is a highly conserved element in placentals, marsupials, and monotremes, whereas it is absent in nonmammalian vertebrates. Following an in silico paleogenomic strategy based on genome-wide searches for paralog sequences, we discovered that opossum and wallaby nPE2 sequences are highly similar to members of the superfamily of CORE-short interspersed nucleotide element (SINE) retroposons, in particular to MAR1 retroposons that are widely present in marsupial genomes. Thus, the neuronal enhancer nPE2 originated from the exaptation of a CORE-SINE retroposon in the lineage leading to mammals and remained under purifying selection in all mammalian orders for the last 170 million years. Expression studies performed in transgenic mice showed that two nonadjacent nPE2 subregions are essential to drive reporter gene expression into POMC hypothalamic neurons, providing the first functional example of an exapted enhancer derived from an ancient CORE-SINE retroposon. In addition, we found that this CORE-SINE family of retroposons is likely to still be active in American and Australian marsupial genomes and that several highly conserved exonic, intronic and intergenic sequences in the human genome originated from the exaptation of CORESINE retroposons. Together, our results provide clear evidence of the functional novelties that transposed elements contributed to their host genomes throughout evolution. © 2007 Santangelo et al.

Registro:

Documento: Artículo
Título:Ancient exaptation of a CORE-SINE retroposon into a highly conserved mammalian neuronal enhancer of the proopiomelanocortin gene
Autor:Santangelo, A.M.; De Souza, F.S.J.; Franchini, L.F.; Bumaschny, V.F.; Low, M.J.; Rubinstein, M.
Filiación:Instituto de Investigaciones en Ingeniería Genética Y Biología Molecular, Consejo Nacional de Investigaciones Científicas Y Técnicas, Buenos Aires, Argentina
Center for the Study of Weight Regulation and Associated Disorders, Portland, OR, United States
Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, United States
Departmento de Fisiología, Biología Molecular Y Celular, Facultad de Ciencias Exactas Y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Centro de Estudios Científicos, Valdivia, Chile
Palabras clave:proopiomelanocortin; animal experiment; animal tissue; article; brain nerve cell; computer model; embryo; enhancer region; female; gene expression; genetic conservation; genetic database; genetic line; genome analysis; hypothalamus; intron; mammalian genetics; marsupial; molecular evolution; monotremate; mouse; multigene family; newborn; nonhuman; physical anthropology; placenta; reporter gene; retroposon; short interspersed repeat; transposon; vertebrate; Animals; Base Sequence; Computational Biology; Consensus Sequence; Conserved Sequence; Embryonic Development; Enhancer Elements (Genetics); Evolution, Molecular; Gene Expression Regulation, Developmental; Genomics; Mammals; Mice; Mice, Transgenic; Molecular Sequence Data; Neurons; Opossums; Paleontology; Pro-Opiomelanocortin; Sequence Alignment; Sequence Analysis, DNA; Sequence Deletion; Short Interspersed Nucleotide Elements; Didelphidae; Eutheria; Gnathostomata (vertebrate); Mammalia; Metatheria; Monotremata; Mus musculus; Vertebrata
Año:2007
Volumen:3
Número:10
Página de inicio:1813
Página de fin:1826
DOI: http://dx.doi.org/10.1371/journal.pgen.0030166
Título revista:PLoS Genetics
Título revista abreviado:PLoS Genet.
ISSN:15537390
CAS:proopiomelanocortin, 66796-54-1; Pro-Opiomelanocortin, 66796-54-1
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_15537390_v3_n10_p1813_Santangelo.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15537390_v3_n10_p1813_Santangelo

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Citas:

---------- APA ----------
Santangelo, A.M., De Souza, F.S.J., Franchini, L.F., Bumaschny, V.F., Low, M.J. & Rubinstein, M. (2007) . Ancient exaptation of a CORE-SINE retroposon into a highly conserved mammalian neuronal enhancer of the proopiomelanocortin gene. PLoS Genetics, 3(10), 1813-1826.
http://dx.doi.org/10.1371/journal.pgen.0030166
---------- CHICAGO ----------
Santangelo, A.M., De Souza, F.S.J., Franchini, L.F., Bumaschny, V.F., Low, M.J., Rubinstein, M. "Ancient exaptation of a CORE-SINE retroposon into a highly conserved mammalian neuronal enhancer of the proopiomelanocortin gene" . PLoS Genetics 3, no. 10 (2007) : 1813-1826.
http://dx.doi.org/10.1371/journal.pgen.0030166
---------- MLA ----------
Santangelo, A.M., De Souza, F.S.J., Franchini, L.F., Bumaschny, V.F., Low, M.J., Rubinstein, M. "Ancient exaptation of a CORE-SINE retroposon into a highly conserved mammalian neuronal enhancer of the proopiomelanocortin gene" . PLoS Genetics, vol. 3, no. 10, 2007, pp. 1813-1826.
http://dx.doi.org/10.1371/journal.pgen.0030166
---------- VANCOUVER ----------
Santangelo, A.M., De Souza, F.S.J., Franchini, L.F., Bumaschny, V.F., Low, M.J., Rubinstein, M. Ancient exaptation of a CORE-SINE retroposon into a highly conserved mammalian neuronal enhancer of the proopiomelanocortin gene. PLoS Genet. 2007;3(10):1813-1826.
http://dx.doi.org/10.1371/journal.pgen.0030166