Interspecific Introgressive Origin of Genomic Diversity in the House Mouse
ABSTRACT: We report on a genome-wide scan for introgression in the house mouse (Mus musculus domesticus) involving the Algerian mouse (Mus spretus), using 20 samples from the ranges of sympatry and allopatry. Our analysis reveals significant variability in introgression signatures along the genomes, as well as across the samples. We find that fewer than half of the chromosomes in each genome harbor all detectable introgression. Further, a surprising result is that European mice carry more M. spretus alleles than the sympatric African ones. Using the length distribution and sharing patterns of introgressed genomic tracts across the samples, we propose three hypotheses. First, at least three distinct hybridization events involving M. spretus have occurred, one of which is ancient, and the other two are recent. Second, several of the inferred introgressed tracts contain genes that are likely to confer adaptive advantage. Third, introgressed tracts might contain driver genes that determine the evolutionary fate of those tracts. Further, our analysis revealed introgressed genes of functional importance, including the Vkorc1 gene, which is implicated in rodenticide resistance, and olfactory receptor genes. Our findings highlight the extent and role of introgression in nature, and call for careful analysis and interpretation of house mouse data in evolutionary and genetic studies. Six wild M. m. domesticus samples were genotyped using the Affymetrix Mouse Diversity Genotyping Array.
Project description:In development, timing is of the utmost importance, and the timing of various developmental processes are often changed during evolution. We measured the timing of gene expression changes in the brains of two species of mice throughout postnatal development. Mus musculus and Mus spretus mice were bred at the MPI-EVA mouse facility. Whole brain samples were collected from mice of 3 different age classes: newborns, pups and young adults. RNA extracted from the dissected tissue was hybridized to Affymetrix MG-430 2.0 GeneChip arrays.
Project description:Malaria infection triggers vigorous host immune responses; however, the parasite ligands, host receptors and the signaling pathways responsible for these reactions remain unknown or controversial. Malaria parasites primarily reside within red blood cells (RBCs), thereby hiding themselves from direct contact and recognition by host immune cells. Host responses to malaria infection are very different from those elicited by bacterial and viral infections and the host receptors recognizing parasite ligands have been elusive. Here we investigated mouse genome-wide transcriptional responses to infections with two strains of Plasmodium yoelii (N67 and N67C) and discovered differences in innate response pathways corresponding to strain-specific disease phenotypes. Using in vitro RNAi gene knockdown and knockout mice, we demonstrated that a strong IFN-I response triggered by RNA Polymerase III and melanoma differentiation-associated protein 5 (MDA5), not Toll-like receptors (TLRs), binding of parasite DNA/RNA contributed to a decline of parasitemia in N67-infected mice. We showed that conventional dendritic cells were the major sources of early IFN-I, and that surface expression of phosphatidylserine (PS) on infected RBC (iRBC) might promote their phagocytic uptake, leading to the release of parasite ligands and the IFN-I response in N67 infection. In contrast, an elevated inflammatory response mediated by CD14/TLR and p38 signaling played a role in disease severity and early host death in N67C-infected mice. In addition to identifying cytosolic DNA/RNA sensors and signaling pathways previously unrecognized in malaria infection, our study demonstrates the importance of parasite genetic backgrounds in malaria pathology and provides important information for studying human malaria pathogenesis. Spleen RNA from mice, 4 days post infection with Plasmodium yoelii (strain N67 or N67C), or mock infection (N). Replicates from 6 individual mice per condition.
Project description:RNA was extracted from adult male and adult female Drosophila simulans carrying small genomic segments introgressed from Drosophila mauritiana Overall design: Seven introgression genotypes were profiled, as well as the parental D. simulans and D. mauritiana strains. Each sex-by-genotype was assayed on four replicate arrays incorporating a dye swap
Project description:Currently there is growing concern with respect to scenarios where people are likely to be presented with radiation exposure along with many kinds of other injuries such as trauma and infection. The potential for such scenarios was brought to reality with the events and aftermath of the Fukushima nuclear disaster in Japan. As such medical complications arising from such exposures would be poorly dealt with as no evidence-based guidelines exist for their rehabilitation or recovery. Our research intends to differentially characterize combined radiation and burn injuries and identify novel pathways and biomarkers. Such findings will lead to better medical practices in the diagnosis, care and rehabilitation of affected individuals. The study includes four groups of mice: 1) Control sham mice group (n=4), 2) Skin burn injury mice group (n=6), 3) Radiation injury mice group (n=6), 4) Combined radiation and burn injury mice group (n=6). We propose to characterize the effects of combined radiation and burn injuries using microRNA microarray analysis. Our primary aim is to identify novel molecular pathways and biomarkers specific to whole blood samples (serum) from mice exposed to combined radiation and burn injuries. B6D2F1/J female mice will be used. 30 days following combined radiation and burn injuries arterial blood will be harvested from euthanized mice. 200ul of serum from whole blood samples will be used for microRNA microarray experiments (Affymetrix).
Project description:Comparison between wild-type and cardiomyocyte-restricted knock-out of IL6 cytokines receptor component gp130 after surgical intervention for pressure-overload induced cardiomyopathy.
Project description:Lean male mice were fed a high fat diet (HFD, lard 24% w/w) for 16 weeks. At 9 weeks, when all hallmarks of prediabetes were established, groups of mice were treated with drug (metformin, glibenclamide, sitagliptin, rosiglitazone, pioglitazone, fenofibrate, T0901317, atorvastatin, salicylate or rofecoxib) for another 7 weeks together with the high fat diet. An additional group was switched back to a chow diet (dietary lifestyle intervention) after the first 9 weeks of high fat diet. All groups were compared to a control group receiving HFD alone and to a reference group fed chow (baseline reference) for the entire experimental period (16 weeks).
Project description:Lean male mice were fed a high fat diet (HFD, lard 24% w/w) for 16 weeks. At 9 weeks, when all hallmarks of prediabetes were established, groups of mice were treated with drug (rosiglitazone, pioglitazone, T0901317, or salicylate) for another 7 weeks together with the high fat diet. An additional group was switched back to a chow diet (dietary lifestyle intervention) after the first 9 weeks of high fat diet. All groups were compared to a control group receiving HFD alone and to a reference group fed chow (baseline reference) for the entire experimental period (16 weeks). One group (n=9) remained on maintenance chow throughout the entire study period (16 weeks) and served as healthy, age-matched control. After the nine week run-in period, the HFD fed mice were matched into thirteen groups based on body weight. The first group (n=9) was sacrificed immediately after matching. The second group (n=15) was continued on HFD until the end of the experiment at t=16 weeks. The fourth group (n=9) was switched to regular chow (dietary lifestyle intervention). The other groups (each n=9) continued on HFD supplemented with drugs typically used in clinical practice. More specifically, following drugs were mixed into HFD ; rosiglitazone (0.010% w/w), pioglitazone (0.010% w/w), T0901317 (0.010% w/w) and salicylate (0.40% w/w).
Project description:Purpose: The goals of this study are to compare next-generation sequencing-derived hippocampal transcriptome profiling from mice lacking hippocampal Acetycholine release to evaluate the role of the neurotransmitter in hippocampal gene expression.