Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
Project description:According to recent reports, exposure to environmental endocrine disrupting chemicals (EDs) during pregnancy may harm multiple subsequent generations. We hypothesized that EDs must directly alter DNA methylation and/or transcription in the exposed fetal germ cells to affect the grandchild. In addition, the aberrant pattern must be retained in the germ cells of the grandchild -- withstanding global epigenome remodeling -- to affect the great-grandchild. To test this hypothesis, we extensively searched for immediate and persistent epigenetic effects in purified germ cells of the exposed fetus and those of the next generation. We treated gestating female mice with previously validated doses of vinclozolin (VZ), bisphenol A (BPA), di-(2-ethylhexyl) phthalate (DEHP), or control oil, during the time when the prospermatogonia of the exposed fetus undergo global de novo DNA methylation. Using genome-wide assays, we detected changes in transcription and DNA methylation in the exposed prospermatogonia but these did not persist into the prospermatogonia of the next generation. There was no evidence for transgenerational inheritance of these epigenetic aberrations. Our results suggest that EDs exert direct epigenetic effects in the exposed fetal germ cells, but the germline corrects against deleterious effects in the next generation. Pregnant mice were gavaged daily with endocrine distruptors (VZ at 100 mg/kg/day, DEHP at 750 mg/kg/day, BPA at 0.2 mg/kg/day or control oil) starting at 12.5 days post coitum (dpc) and the G1R germ cells were purified from the exposed fetuses at 17.5 dpc. The G2R germ cells were purified from fetuses that were sired by males that had been treated in utero in a G0 mother. G1R spermatozoa were collected from adult males that had been treated in utero at the fetal stages. G2R spermatozoa were collected from adult males who were sired by in-uteo-treated males.
Project description:According to recent reports, exposure to environmental endocrine disrupting chemicals (EDs) during pregnancy may harm multiple subsequent generations. We hypothesized that EDs must directly alter DNA methylation and/or transcription in the exposed fetal germ cells to affect the grandchild. In addition, the aberrant pattern must be retained in the germ cells of the grandchild -- withstanding global epigenome remodeling -- to affect the great-grandchild. To test this hypothesis, we extensively searched for immediate and persistent epigenetic effects in purified germ cells of the exposed fetus and those of the next generation. We treated gestating female mice with previously validated doses of vinclozolin (VZ), bisphenol A (BPA), di-(2-ethylhexyl) phthalate (DEHP), or control oil, during the time when the prospermatogonia of the exposed fetus undergo global de novo DNA methylation. Using genome-wide assays, we detected changes in transcription and DNA methylation in the exposed prospermatogonia but these did not persist into the prospermatogonia of the next generation. There was no evidence for transgenerational inheritance of these epigenetic aberrations. Our results suggest that EDs exert direct epigenetic effects in the exposed fetal germ cells, but the germline corrects against deleterious effects in the next generation. Pregnant mice were gavaged daily with endocrine distruptors (VZ at 100 mg/kg/day, DEHP at 750 mg/kg/day, BPA at 0.2 mg/kg/day or control oil) starting at 12.5 days post coitum (dpc) and the G1R germ cells were purified from the exposed fetuses at 17.5 dpc. The G2R germ cells were purified from fetuses that were sired by males that had been treated in utero in a G0 mother. G1R spermatozoa were collected from adult males that had been treated in utero at the fetal stages. G2R spermatozoa were collected from adult males who were sired by in-uteo-treated males.