Birth of the mammalian proopiomelanocortin (POMC) gene neuron-specific enhancers nPE1 and nPE2: a story of exaptation.

LUCÍA F. FRANCHINI, FLÁVIO JS DESOUZA, RODRIGO LÓPEZ-LEAL AND MARCELO RUBINSTEIN.

Barcelona

Congreso; Society for Molecular Biology and Evolution; 2008

POMC expression in the mammalian brain is controlled by a distal upstream module containing two neuronal enhancers, nPE1 and nPE2. To study the functional role of these two enhancers we generated several transgenic mouse pedigrees expressing either a red or a green fluorescent protein under the transcriptional control of nPE1 or nPE2, respectively. Brain slices obtained from various double transgenic mice showed that nPE1 and nPE2 may drive reporter gene expression to identical POMC neurons. Despite their overlapping function, nPE1 and nPE2 seem to have originated from independent evolutionary processes; whereas nPE2 is under purifying selection in all Mammals, nPE1 is just present in Eutheria. To determine the evolutionary origin of these two enhancers we followed an in silico paleogenomic strategy based on paralog sequence searches in most available genomes. We found that nPE2 originated from the exaptation of a CORE-SINE retroposon in the lineage leading to mammals whereas nPE1 is derived from a MaLR, a member of the LTRs retrotransposon family widespread in placental mammals. In summary, two independent retroposition insertions upstream of POMC evolved into enhancer sequences that POMC neuron specific expression in the same subset of hypothalamic neurons, probably binding the same combination of transcription factors.