Genetic variation in the developmental regulation of cortical avpr1a among prairie voles.

Early experiences can have enduring impacts on brain and behavior, but the strength of these effects can be influenced by genetic variation. In principle, polymorphic CpGs (polyCpGs) may contribute to gene-by-environment interactions (G × E) by altering DNA methylation. In this study, we investigate the influence of polyCpGs on the development of vasopressin receptor 1a abundance in the retrosplenial cortex (RSC-V1aR) of prairie voles (Microtus ochrogaster). Two alternative alleles ('HI'/'LO') predict RSC avpr1a expression, V1aR abundance and sexual fidelity in adulthood; these alleles differ in the frequency of CpG sites and in methylation at a putative intron enhancer. We hypothesized that the elevated CpG abundance in the LO allele would make homozygous LO/LO voles more sensitive to developmental perturbations. We found that genotype differences in RSC-V1aR abundance emerged early in ontogeny and were accompanied by differences in methylation of the putative enhancer. As predicted, postnatal treatment with an oxytocin receptor antagonist (OTA) reduced RSC-V1aR abundance in LO/LO adults but not their HI/HI siblings. Similarly, methylation inhibition by zebularine increased RSC-V1aR in LO/LO adults, but not in HI/HI siblings. These data show a gene-by-environment interaction in RSC-V1aR. Surprisingly, however, neither OTA nor zebularine altered adult methylation of the intronic enhancer, suggesting that differences in sensitivity could not be explained by CpG density at the enhancer alone. Methylated DNA immunoprecipiation-sequencing showed additional differentially methylated regions between HI/HI and LO/LO voles. Future research should examine the role of these regions and other regulatory elements in the ontogeny of RSC-V1aR and its developmentally induced changes.

Low genetic diversity and local adaptive divergence of Dracaena cambodiana (Liliaceae) populations associated with historical population bottlenecks and natural selection: an endangered long-lived tree endemic to Hainan Island, China.

Historical population bottlenecks and natural selection have important effects on the current genetic diversity and structure of long-lived trees. Dracaena cambodiana is an endangered, long-lived tree endemic to Hainan Island, China. Our field investigations showed that only 10 populations remain on Hainan Island and that almost all have been seriously isolated and grow in distinct habitats. A considerable amount of genetic variation at the species level, but little variation at the population level, and a high level of genetic differentiation among the populations with limited gene flow in D. cambodiana were detected using inter-simple sequence repeat (ISSR) and random amplified polymorphic DNA (RAPD) analyses. No significant correlation was found between genetic diversity and actual population size, as the genetic diversities were similar regardless of population size. The Mantel test revealed that there was no correlation between genetic and geographic distances among the 10 populations. The UPGMA, PCoA and Bayesian analyses showed that local adaptive divergence has occurred among the D. cambodiana populations, which was further supported by habitat-private fragments. We suggest that the current genetic diversity and population differentiation of D. cambodiana resulted from historical population bottlenecks and natural selection followed by historical isolation. However, the lack of natural regeneration of D. cambodiana indicates that former local adaptations with low genetic diversity may have been genetically weak and are unable to adapt to the current ecological environments.

Murine pancreatic beta TC3 cells show greater 2', 5'-oligoadenylate synthetase (2'5'AS) antiviral enzyme activity and apoptosis following IFN-alpha or poly(I:C) treatment than pancreatic alpha TC3 cells.

Type 1 diabetes is caused by autoimmune destruction of pancreatic beta cells, possibly virus initiated. Virus infection induces alpha-interferon (IFN-alpha), leading to upregulation of genes encoding double-stranded (ds) RNA-dependent antiviral enzymes 2', 5'-oligoadenylate synthetase (2'5'AS) and PKR (p68). To investigate whether beta cell specificity could be due to antiviral differences between beta and alpha cells, we treated beta and alpha TC3 cell lines with IFN-alpha and/or poly(I:C) (a synthetic dsRNA). Results showed that, following IFN-alpha stimulation, increases in 2'5'AS levels and activities were significantly higher in beta than alpha cells (P < .001), whereas increases in PKR level and activity were comparable in the two cell types. Poly(I:C) stimulated 2'5'AS activity in beta but not alpha cells, and co-transfection IFN-alpha plus poly(I:C) induced apoptosis in beta but not alpha cells. These findings suggest that the elevated 2'5'AS response of pancreatic beta cells could render them particularly vulnerable to damage and/or apoptosis during virus infection.