IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
Convergent evolution of two mammalian neuronal enhancers by sequential exaptation of unrelated retroposons
Autor/es:
LUCIA F. FRANCHINI; RODRIGO LÓPEZ-LEAL; SOFIA NASIF; PAULA BEATI; DIEGO M. GELMAN; MALCOM J. LOW; FLAVIO S. J. DE SOUZA; MARCELO RUBINSTEIN
Revista:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Editorial:
NATL ACAD SCIENCES
Referencias:
Lugar: Washington DC, USA; Año: 2011 vol. 108 p. 15270 - 17275
ISSN:
0027-8424
Resumen:
The proopiomelanocortin gene (POMC) is expressed in a group
of neurons present in the arcuate nucleus of the hypothalamus.
Neuron-specific POMC expression in mammals is conveyed by
two distal enhancers, named nPE1 and nPE2. Previous transgenic
mouse studies showed that nPE1 and nPE2 independently drive
reporter gene expression to POMC neurons. Here, we investigated
the evolutionary mechanisms that shaped not one but two neuron-
specific POMC enhancers and tested whether nPE1 and nPE2
drive identical or complementary spatiotemporal expression patterns.
Sequence comparison among representative genomes of
most vertebrate classes and mammalian orders showed that
nPE1 is a placental novelty. Using in silico paleogenomics we
found that nPE1 originated from the exaptation of a mammalian-
apparent LTR retrotransposon sometime between the metatherian/
eutherian split (147 Mya) and the placental mammal
radiation (z90 Mya). Thus, the evolutionary origin of nPE1 differs,
in kind and time, from that previously demonstrated for nPE2,
which was exapted from a CORE-short interspersed nucleotide
element (SINE) retroposon before the origin of prototherians,
166 Mya. Transgenic mice expressing the fluorescent markers
tomato and EGFP driven by nPE1 or nPE2, respectively, demonstrated
coexpression of both reporter genes along the entire arcuate
nucleus. The onset of reporter gene expression guided by
nPE1 and nPE2 was also identical and coincidental with the onset
of Pomc expression in the presumptive mouse diencephalon.
Thus, the independent exaptation of two unrelated retroposons
into functional analogs regulating neuronal POMC expression constitutes
an authentic example of convergent molecular evolution
of cell-specific enhancers.