RESUMEN
The hypothesis that p53 deficiency enhances the survival of DNA-damage bearing cells was investigated in wild-type and p53 mutant embryonic stem (ES) cells. Following UV-C irradiation, p53 is rapidly induced in wild-type cells and p53-dependent apoptosis follows within 8 h, resulting in the death of the majority of cells within 36 h. Increasing doses of UV-irradiation resulted in enhanced clonogenic survival of null cells as compared to wild-type. Amongst surviving clones, the Hprt mutation frequency was found to be dependent upon UV dose and influenced by p53 status. Treatment with ionizing radiation led to enhanced expression of p53 but resulted in little induction of apoptosis irrespective of p53 status. However, clonogenic potential was considerably reduced, particularly in wild-type cells which showed a tenfold lower survival than null cells. In contrast to the effects of UV-irradiation, the incidence of Hprt mutation did not differ significantly between wild-type and p53 null survivors. The data confirm that p53 restricts the numbers of cells bearing mutations that survive DNA damage induced by either agent, albeit by different mechanisms.
Asunto(s)
Apoptosis/genética , Daño del ADN , Genes p53 , Mutación/genética , Proteína p53 Supresora de Tumor/fisiología , Animales , Ensayo de Unidades Formadoras de Colonias , Rayos gamma , Hipoxantina Fosforribosiltransferasa/genética , Ratones , Células Madre/metabolismo , Células Madre/efectos de la radiación , Proteína p53 Supresora de Tumor/biosíntesis , Proteína p53 Supresora de Tumor/deficiencia , Rayos UltravioletaRESUMEN
Genetic variability within the blue (Connochaetes taurinus) and black (C. gnou) wildebeests in South Africa was estimated from allozyme frequencies at 31 protein-encoding loci. Seven loci, Ak-1, Alb, Est-D, Icdh-1, Mpi-1, Pgm-1, and Tf, were polymorphic in the blue wildebeest, but only two loci, Est-D and Tf, were variable in its congener. Average gene diversity was H = 0.018 +/- 0.013 in the black wildebeest and was significantly smaller than that, H = 0.081 +/- 0.030, in the blue wildebeest. The reduced level of heterozygosity in black wildebeest is most likely due to a bottleneck in population size in the early 1900s. The genetic distance between the two species was 0.059 +/- 0.027, which is consistent with an estimate of low mtDNA sequence divergence found previously.
Asunto(s)
Antílopes/genética , Isoenzimas/genética , Polimorfismo Genético , África Austral , Animales , Electroforesis en Gel de Almidón , Frecuencia de los Genes , Heterocigoto , Especificidad de la EspecieRESUMEN
The blue and the black wildebeest, Connochaetes taurinus and C. gnou, are currently classified as congeneric, but previous reports have placed C. taurinus in its own genus, Gorgon. To further clarify the evolutionary relationship between these two species, we examined and compared their mitotic chromosomes and mitochondrial DNA (mtDNA). No species-specific G-banded or C-banded chromosomal markers were found, and we conclude that the karyotypes are invariant at the level of resolution obtained. An evolutionary divergence time of approximately 1 million years was calculated from mtDNA restriction fragment data, indicating a close phylogenetic relationship for the two wildebeest species. The low nucleotide diversity detected within the black wildebeest (0.09%) is thought to reflect the recent population bottleneck to which the species has been subjected. In contrast, the limited heterogeneity (0.02%) within the South African blue wildebeest herds sampled in this study was surprising, and we argue that for many populations, especially those on smaller reserves, this may reflect common descent from a small number of animals through management-controlled translocations.