RESUMO
In this minireview, we highlight the contributions of the late Austin L. Hughes to two areas of molecular evolution: the role of positive (Darwinian) selection, and the impact of gene duplications during genome evolution.
Assuntos
Adaptação Fisiológica/genética , Evolução Biológica , Duplicação Gênica , Genoma , Seleção Genética/genética , Animais , HumanosRESUMO
Two new genome sequences confirm that a whole genome duplication occurred in an ancestor of Saccharomyces cerevisiae. This left a legacy of about 500 pairs of duplicated genes, many of which contribute to this yeast's ability to ferment glucose anaerobically; a few have been evolving so quickly they retain almost no sequence similarity to each other.
Assuntos
Evolução Molecular , Genes Duplicados/genética , Genoma Fúngico , Filogenia , Saccharomyces cerevisiae/genética , Sequência de Bases , Bases de Dados Genéticas , Ordem dos Genes , Variação Genética , Poliploidia , Homologia de SequênciaRESUMO
Seizures have been shown to promote the proliferation of granule cell precursors in the adult brain, but the underlying mechanisms remain largely unknown. Using systemic bromodeoxyuridine (BrdU) to label dividing cells, we examined the effects of selective ionotropic glutamate receptor antagonists on granule cell precursor proliferation in adult rats after pentylenetrazol (PTZ)-induced generalized clonic seizures. We found that the NMDA receptor antagonist MK-801 significantly inhibited behavioral and EEG seizures and completely blocked seizure-induced increase in the number of BrdU-labeled cells in the dentate gyrus. Although the AMPA/KA receptor antagonist DNQX was not observed to affect seizures, it significantly suppressed the number of BrdU-labeled cells in the dentate gyrus. Double immunohistochemical staining showed that both the mature granule cells and the majority of BrdU-labeled, mitotically active cells expressed the NMDA receptor subunit NR1 and the AMPA/KA receptor subunit GluR2. Because accumulated evidence showed that mild seizures are sufficient to promote precursor cell proliferation, the present findings that MK-801 inhibited seizures and completely blocked seizure-induced increase in precursor cell proliferation suggest that the direct blockade action of MK-801 on NMDA receptors on the granule cell precursors may play an important role in blocking seizure-induced precursor cell proliferation. The suppression of seizure-induced proliferation of granule cell precursors by DNQX may be achieved by the direct action of DNQX on AMPA/KA receptors on the granule cell precursors. Thus, our findings indicate that seizures may promote cell proliferation in the adult rat dentate gyrus through glutamatergic mechanisms acting on both NMDA and AMPA/KA receptors.
Assuntos
Giro Denteado/patologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Neurônios/efeitos dos fármacos , Receptores de Glutamato/efeitos dos fármacos , Convulsões/patologia , Células-Tronco/efeitos dos fármacos , Animais , Contagem de Células , Proliferação de Células/efeitos dos fármacos , Giro Denteado/efeitos dos fármacos , Giro Denteado/crescimento & desenvolvimento , Maleato de Dizocilpina/farmacologia , Regulação para Baixo , Masculino , Neurônios/patologia , Pentilenotetrazol , Quinoxalinas/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de AMPA/efeitos dos fármacos , Receptores de AMPA/metabolismo , Receptores de Glutamato/metabolismo , Receptores de Ácido Caínico/efeitos dos fármacos , Receptores de Ácido Caínico/metabolismo , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/metabolismo , Convulsões/induzido quimicamenteRESUMO
The molecular mechanisms that regulate gene expression can evolve either by changing the cis-acting DNA elements in promoters, or by replacing the trans-acting regulatory proteins. New data from yeast species show that both processes can happen.