CONVERGENT EVOLUTION OF TWO MAMMALIAN NEURONAL ENHANCERS BY SEQUENTIAL EXAPTATION OF UNRELATED RETROTRANSPOSONS

RUBINSTEIN M, LÓPEZ-LEAL R, NASIF S, BEATI P, DE SOUZA FJS. FRANCHINI LF

Cataratas del Iguazú

Simposio; Gene Expression and RNA Processing Symposium; 2011

ICGEB-ANPCYT-CONICET

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 conserved 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 investigate the evolutionary mechanisms that shaped not one but two neuron-specific POMC enhancers, and tested whether nPE1 and nPE2 drive identical or complementary spatio-temporal 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 discovered that nPE1 originated from the exaptation of a Mammalian-apparent LTR Retrotransposon (MaLR) sometime between the metatherian/eutherian split (147 MYA) and the placental mammal radiation (~90 MYA). Thus, the evolutionary origin of nPE1 differs, in kind and time, from that previously demonstrated for nPE2 which was exapted from a CORE-SINE retrotransposon before the origin of prototherians, 166 MYA. Analysis of compound transgenic mice expressing the fluorescent markers tomato and EGFP under the transcriptional control of 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 acting as neuron-specific enhancers of POMC constitute an authentic first example of convergent molecular evolution of cell-specific enhancers.