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Pupfish (genus Cyprinodon) persist in a series of isolated warm springs in Death Valley. Here we describe an analysis of microsatellite variation at six loci for nine populations encompassing three distinct taxa. Levels of genetic variation within populations and the pattern of relatedness among populations are best explained by spring elevation. Springs at higher elevations harbored less variation and exhibited greater among population divergence than lower elevation springs. This pattern reflects regional paleohydrological history showing a declining water table over the last 20,000 years. Continuing decline of the water table, a trend accelerated by local ground water mining, portends a future of increasing isolation and declining within-population variation. 相似文献
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Identification of a motif in the C terminus of herpes simplex virus regulatory protein ICP4 that contributes to activation of transcription. 总被引:3,自引:0,他引:3 下载免费PDF全文
Expression of most viral genes during productive infection by herpes simplex virus is regulated by the viral protein ICP4 (also called IE175 or Vmw175). The N-terminal portion of ICP4 contains well-defined transactivation, DNA binding, and dimerization domains that contribute to promoter regulation. The C-terminal half of ICP4 contributes to the activity of ICP4, but the functional motifs have not been well mapped. To localize functional motifs in the C-terminal half of ICP4, we have compared the relative specific activities of ICP4 variants in transient-transfection assays. Deletion of the C-terminal 56 residues reduces the specific activity more than 10-fold. Mutational analysis identified three consecutive residues (1252 to 1254) that are conserved in ICP4 orthologs and are essential for full activity, especially in the context of ICP4 variants with a deletion in the N-terminal transactivation domain. Recombinant viruses that encode variants of ICP4 with mutations in the N-terminal transactivation domain and/or the extreme C terminus were constructed. The phenotypes of these recombinant viruses support the hypothesis that efficient promoter activation by ICP4 requires motifs at both the N and C termini. The data suggest that the C terminus of ICP4 functions not as an independent transactivation domain but as an enhancer of the ICP4 N-terminal transactivation domain. The data provide further support for the hypothesis that some ICP4 motifs required for promoter activation are not required for promoter repression and suggest that ICP4 utilizes different cellular factors for activation or repression of viral promoters. 相似文献
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Ryan Wilcox Bryan E Welm Jeffrey T Chang Evan Johnson Avrum Spira Stefanie S Jeffrey Andrea H Bild 《Molecular systems biology》2011,7(1)
Identifying the best drug for each cancer patient requires an efficient individualized strategy. We present MATCH (M erging genomic and pharmacologic A nalyses for T herapy CH oice), an approach using public genomic resources and drug testing of fresh tumor samples to link drugs to patients. Valproic acid (VPA) is highlighted as a proof‐of‐principle. In order to predict specific tumor types with high probability of drug sensitivity, we create drug response signatures using publically available gene expression data and assess sensitivity in a data set of >40 cancer types. Next, we evaluate drug sensitivity in matched tumor and normal tissue and exclude cancer types that are no more sensitive than normal tissue. From these analyses, breast tumors are predicted to be sensitive to VPA. A meta‐analysis across breast cancer data sets shows that aggressive subtypes are most likely to be sensitive to VPA, but all subtypes have sensitive tumors. MATCH predictions correlate significantly with growth inhibition in cancer cell lines and three‐dimensional cultures of fresh tumor samples. MATCH accurately predicts reduction in tumor growth rate following VPA treatment in patient tumor xenografts. MATCH uses genomic analysis with in vitro testing of patient tumors to select optimal drug regimens before clinical trial initiation. 相似文献
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