Gene regulation and speciation in house mice.
Ontology highlight
ABSTRACT:
SUBMITTER: Mack KL
PROVIDER: S-EPMC4817769 | biostudies-literature | 2016 Apr
REPOSITORIES: biostudies-literature
Publications
Gene regulation and speciation in house mice.
Mack Katya L KL Campbell Polly P Nachman Michael W MW
Genome research 20160201 4
One approach to understanding the process of speciation is to characterize the genetic architecture of post-zygotic isolation. As gene regulation requires interactions between loci, negative epistatic interactions between divergent regulatory elements might underlie hybrid incompatibilities and contribute to reproductive isolation. Here, we take advantage of a cross between house mouse subspecies, where hybrid dysfunction is largely unidirectional, to test several key predictions about regulator ...[more]
Similar Datasets
Project description:Changes in cis-regulatory regions are thought to play a major role in the genetic basis of adaptation. However, few studies have linked cis-regulatory variation with adaptation in natural populations. Here, using a combination of exome and RNA-seq data, we performed expression quantitative trait locus (eQTL) mapping and allele-specific expression analyses to study the genetic architecture of regulatory variation in wild house mice (Mus musculus domesticus) using individuals from five populations collected along a latitudinal cline in eastern North America. Mice in this transect showed clinal patterns of variation in several traits, including body mass. Mice were larger in more northern latitudes, in accordance with Bergmann's rule. We identified 17 genes where cis-eQTLs were clinal outliers and for which expression level was correlated with latitude. Among these clinal outliers, we identified two genes (Adam17 and Bcat2) with cis-eQTLs that were associated with adaptive body mass variation and for which expression is correlated with body mass both within and between populations. Finally, we performed a weighted gene co-expression network analysis (WGCNA) to identify expression modules associated with measures of body size variation in these mice. These findings demonstrate the power of combining gene expression data with scans for selection to identify genes involved in adaptive phenotypic evolution, and also provide strong evidence for cis-regulatory elements as essential loci of environmental adaptation in natural populations.
| S-EPMC6211637 | biostudies-literature
Project description:In mammals, intrinsic postzygotic isolation has been well studied in males but has been less studied in females, despite the fact that female gametogenesis and pregnancy provide arenas for hybrid sterility or inviability that are absent in males. Here, we asked whether inviability or sterility is observed in female hybrids of Mus musculus domesticus and M. m. musculus, taxa which hybridize in nature and for which male sterility has been well characterized. We looked for parent-of-origin growth phenotypes by measuring adult body weights in F1 hybrids. We evaluated hybrid female fertility by crossing F1 females to a tester male and comparing multiple reproductive parameters between intrasubspecific controls and intersubspecific hybrids. Hybrid females showed no evidence of parent-of-origin overgrowth or undergrowth, providing no evidence for reduced viability. However, hybrid females had smaller litter sizes, reduced embryo survival, fewer ovulations, and fewer small follicles relative to controls. Significant variation in reproductive parameters was seen among different hybrid genotypes, suggesting that hybrid incompatibilities are polymorphic within subspecies. Differences in reproductive phenotypes in reciprocal genotypes were observed and are consistent with cyto-nuclear incompatibilities or incompatibilities involving genomic imprinting. These findings highlight the potential importance of reduced hybrid female fertility in the early stages of speciation.
| S-EPMC4573315 | biostudies-literature
Project description:The Dobzhansky-Muller (DM) model provides a widely accepted mechanism for the evolution of reproductive isolation: incompatible substitutions disrupt interactions between genes. To date, few candidate incompatibility genes have been identified, leaving the genes driving speciation mostly uncharacterized. The importance of interactions in the DM model suggests that gene coexpression networks provide a powerful framework to understand disrupted pathways associated with postzygotic isolation. Here, we perform weighted gene coexpression network analysis to infer gene interactions in hybrids of two recently diverged European house mouse subspecies, Mus mus domesticus and M. m. musculus, which commonly show hybrid male sterility or subfertility. We use genome-wide testis expression data from 467 hybrid mice from two mapping populations: F2s from a laboratory cross between wild-derived pure subspecies strains and offspring of natural hybrids captured in the Central Europe hybrid zone. This large data set enabled us to build a robust consensus network using hybrid males with fertile phenotypes. We identify several expression modules, or groups of coexpressed genes, that are disrupted in subfertile hybrids, including modules functionally enriched for spermatogenesis, cilium and sperm flagellum organization, chromosome organization, and DNA repair, and including genes expressed in spermatogonia, spermatocytes, and spermatids. Our network-based approach enabled us to hone in on specific hub genes likely to be influencing module-wide gene expression and hence potentially driving large-effect DM incompatibilities. A disproportionate number of hub genes lie within sterility loci identified previously in the hybrid zone mapping population and represent promising candidate barrier genes and targets for future functional analysis.
| S-EPMC7253214 | biostudies-literature
Project description:Patterns of genetic differentiation among taxa at early stages of divergence provide an opportunity to make inferences about the history of speciation. Here, we conduct a survey of DNA-sequence polymorphism and divergence at loci on the autosomes, X chromosome, Y chromosome and mitochondrial DNA in samples of Mus domesticus, M. musculus and M. castaneus. We analyzed our data under a divergence with gene flow model and estimate that the effective population size of M. castaneus is 200,000-400,000, of M. domesticus is 100,000-200,000 and of M. musculus is 60,000-120,000. These data also suggest that these species started to diverge approximately 500,000 years ago. Consistent with this recent divergence, we observed considerable variation in the genealogical patterns among loci. For some loci, all alleles within each species formed a monophyletic group, while at other loci, species were intermingled on the phylogeny of alleles. This intermingling probably reflects both incomplete lineage sorting and gene flow after divergence. Likelihood ratio tests rejected a strict allopatric model with no gene flow in comparisons between each pair of species. Gene flow was asymmetric: no gene flow was detected into M. domesticus, while significant gene flow was detected into both M. castaneus and M. musculus. Finally, most of the gene flow occurred at autosomal loci, resulting in a significantly higher ratio of fixed differences to polymorphisms at the X and Y chromosomes relative to autosomes in some comparisons, or just the X chromosome in others, emphasizing the important role of the sex chromosomes in general and the X chromosome in particular in speciation.
| S-EPMC2915842 | biostudies-literature
Project description:Niche partitioning and sequence evolution drive genomic and phenotypic divergence, which ultimately leads to bacterial diversification. This study investigated the genomic composition of two Shewanella baltica clades previously identified through multilocus sequencing typing and recovered from the redox transition zone in the central Baltic Sea. Comparative genomic analysis revealed significantly higher interclade than intraclade genomic dissimilarity and that a subset of genes present in clade A were associated with potential adaptation to respiration of sulfur compounds present in the redox transition zone. The transcriptomic divergence between two representative strains of clades A and D, OS185 and OS195, was also characterized and revealed marked regulatory differences. We found that both the transcriptional divergence of shared genes and expression of strain-specific genes led to differences in regulatory patterns between strains that correlate with environmental redox niches. For instance, under anoxic conditions of respiratory nitrate ammonification, OS185-the strain isolated from a nitrate-rich environment-upregulated nearly twice the number of shared genes upregulated by OS195-the strain isolated from an H2S-containing anoxic environment. Conversely, OS195 showed stronger induction of strain-specific genes, especially those associated with sulfur compound respiration, under thiosulfate-reducing conditions. A positive association between the level of transcriptional divergence and the level of sequence divergence for shared genes was also noted. Our results provide further support for the hypothesis that genomic changes impacting transcriptional regulation play an important role in the diversification of ecologically distinct populations.IMPORTANCE This study examined potential mechanisms through which co-occurring Shewanella baltica strains diversified to form ecologically distinct populations. At the time of isolation, the strains studied composed the major fraction of culturable nitrate-reducing communities in the Baltica Sea. Analysis of genomic content of 13 S. baltica strains from two clades representing different ecotypes demonstrated that one clade specifically possesses a number of genes that could favor successful adaptation to respire sulfur compounds in the portion of the water column from which these strains were isolated. In addition, transcriptional profiling of fully sequenced strains representative of these two clades, OS185 and OS195, under oxygen-, nitrate-, and thiosulfate-respiring conditions demonstrated that the strains exhibit relatively similar transcriptional responses during aerobic growth but more-distinct transcriptional responses under nitrate- and thiosulfate-respiring conditions. Results from this study provide insights into how genomic and gene regulatory diversification together impacted the redox specialization of the S. baltica strains.
| S-EPMC5795076 | biostudies-literature
Project description:Background: The Dobzhansky-Muller (D-M) model of speciation by genic incompatibility is widely accepted as the primary cause of interspecific postzygotic isolation. Since the introduction of this model, there have been theoretical and experimental data supporting the existence of such incompatibilities. However, speciation genes have been largely elusive, with only a handful of candidate genes identified in a few organisms. The Saccharomyces sensu stricto yeasts have small genomes, can be easily cultured, and can mate interspecifically to produce sterile hybrids, are thus an ideal model for studying postzygotic isolation. Among them, only a single D-M pair has been found, between S. bayanus and S. cerevisiae, comprising the mitochondrially targeted product of a nuclear gene, AEP2, and a mitochondrially encoded locus, OLI1, the 5' region of whose transcript is bound by Aep2. Thus far, no D-M pair of nuclear genes has been identified between any sensu stricto yeasts. Methods: We report here the first detailed genome-wide analysis of rare F2 progeny from an otherwise sterile hybrid, and show that no classic D-M pairs of speciation genes exist between the nuclear genomes of the closely related yeasts S. cerevisiae and S. paradoxus. Instead, our analyses suggest that more complex interactions may be responsible for their post-zygotic separation. These interactions most likely involve multiple loci having weak effects, as there were multiple significant pairwise combinations of loci, with no single combination being completely excluded from the viable F2s. Conclusions: The lack of a nuclear encoded classic D-M pair between these two yeasts, yet the existence of multiple loci that may each exert a small effect through complex interactions, suggests that initial speciation events might not always be mediated by D-M pairs. An alternative explanation may be that "death by a thousand cuts" leads to speciation, whereby an accumulation of polymorphisms can lead to an incompatibility between the species "transcriptional and metabolic networks, with no single pair at least initially being responsible for the incompatibility. After such a speciation event, it is possible that one or more D-M pairs might subsequently arise following isolation. Genotypes for hybrids between S. cerevisiae and S. paradoxus. A genotyping experiment design type classifies an individual or group of individuals on the basis of alleles, haplotypes, SNP's.
2010-06-08 | GSE19683 | GEO
Project description:Quantitative PCR (qPCR) has been commonly used to measure gene expression in a number of research contexts, but the measured RNA concentrations do not always represent the concentrations of active proteins which they encode. This can be due to transcriptional regulation or post-translational modifications, or localization of immune environments, as can occur during infection. However, in studies using free-living non-model species, such as in ecoimmunological research, qPCR may be the only available option to measure a parameter of interest, and so understanding the quantitative link between gene expression and associated effector protein levels is vital.Here, we use qPCR to measure concentrations of RNA from mesenteric lymph node (MLN) and spleen tissue, and multiplex ELISA of blood serum to measure circulating cytokine concentrations in a wild population of a model species, Mus musculus domesticus.Few significant correlations were found between gene expression levels and circulating cytokines of the same immune genes or proteins, or related functional groups. Where significant correlations were observed, these were most frequently within the measured tissue (i.e., the expression levels of genes measured from spleen tissue were more likely to correlate with each other rather than with genes measured from MLN tissue, or with cytokine concentrations measured from blood).Potential reasons for discrepancies between measures including differences in decay rates and transcriptional regulation networks are discussed. We highlight the relative usefulness of different measures under different research questions and consider what might be inferred from immune assays.
| S-EPMC7771139 | biostudies-literature
Project description:Major urinary proteins (MUPs) are highly homologous proteoforms that function in binding, transporting and releasing pheromones in house mice. The main analytical challenge for studying variation in MUPs, even for state-of-the-art proteomics techniques, is their high degree of amino acid sequence homology. In this study we used unique peptides for proteoform-specific identification. We applied different search engines (ProteinPilot™vs. PEAKS®) and protein databases (MUP database vs. SwissProt + unreviewed MUPs), and found that proteoform identification is influenced by addressing background proteins (unregulated urinary proteins, non-MUPs) during the database search. High resolution Q-TOF mass spectrometry was used to identify and precisely quantify the regulation of MUP proteoforms in male mice that were reared in standard housing and then transferred to semi-natural enclosures (within-subject design). By using a designated MUP database we were able to distinguish 19 MUP proteoforms, with A2CEK6 (a Mup11 gene product) being the most abundant based on spectral intensities. We compared three different quantification strategies based on MS1- (from IDA and SWATH™ spectra) and MS2 (SWATH™) data, and the results of these methods were correlated. Furthermore, three data normalization methods were compared and we found that increased statistical significance of fold-changes can be achieved by normalization based on urinary protein concentrations. We show that male mice living in semi-natural enclosures significantly up-regulated some but not all MUPs (differential regulation), e.g., A2ANT6, a Mup6 gene product, was upregulated between 9-fold (MS1) and 13-fold (MS2) using the designated MUP database. Finally, we show that 85 ± 7% of total MS intensity can be attributed to MUP-derived peptides, which supports the assumption that MUPs are the primary proteins in mouse urine. Our results provide new tools for assessing qualitative and quantitative variation of MUPs and suggest that male mice regulate the expression of specific MUP proteoforms, depending upon social conditions.
| S-EPMC5166567 | biostudies-literature
Project description:The southern house mosquito, Culex quinquefasciatus, is one of the most prevalent vectors of lymphatic filariasis and flavivirus-induced encephalitis. Its vectorial capacity is directly affected by its reproductive feeding behaviors, such as host seeking, blood feeding, resting, and egg laying. In mosquitoes, these gonotrophic behaviors are odor-mediated and regulated following blood feeding. Immediately after a blood meal, female mosquitoes show reduced olfactory responsiveness and flight activity, as they enter a resting state. Insights into antennal chemosensory gene regulation at this time period can provide a foundation to identify targets involved in the state switch between host seeking and resting.This study used quantitative gene expression analyses to explore blood meal induced regulation of chemosensory gene families in the antennae of 6 days post-emergence C. quinquefasciatus females. Improved annotations for multiple chemosensory gene families, and a quantitative differential gene expression analysis between host seeking and 24 h post- blood fed females of the same age, allowed for the detection of transcripts that potentially play a role in the switch from host seeking to resting, in C. quinquefasciatus. The expression profiles of chemosensory genes varied significantly between the two treatments.Annotations for chemosensory gene repertoires in C. quinquefasciatus have been manually curated and corrected for 3' exon choice and transcript length, through sequence and transcriptome analyses. The gene expression analyses identified various molecular components of the peripheral olfactory system in C. quinquefasciatus, including odorant receptors, ionotropic receptors, odorant binding proteins and chemosensory proteins, that are regulated in response to blood feeding, and could be critical for the behavioral switch from host seeking to resting. Functional characterization of these proteins in the future can identify targets essential for the females' gonotrophic behaviors, and can be used to design novel vector control strategies.
| S-EPMC5437716 | biostudies-literature
Project description:Results of electrophoretic surveys have suggested that hemoglobin polymorphism may be maintained by balancing selection in natural populations of house mice, Mus musculus. Here we report a survey of nucleotide variation in the adult globin genes of house mice from South America. We surveyed nucleotide polymorphism in two closely linked alpha-globin paralogs and two closely linked beta-globin paralogs to test whether patterns of variation are consistent with a model of long-term balancing selection. Surprisingly high levels of nucleotide polymorphism at the two beta-globin paralogs were attributable to the segregation of two highly divergent haplotypes, Hbbs (which carries two identical beta-globin paralogs) and Hbbd (which carries two functionally divergent beta-globin paralogs). Interparalog gene conversion on the Hbbs haplotype has produced a highly unusual situation in which the two paralogs are more similar to one another than either one is to its allelic counterpart on the Hbbd haplotype. Levels of nucleotide polymorphism and linkage disequilibrium at the two beta-globin paralogs suggest a complex history of diversity-enhancing selection that may be responsible for long-term maintenance of alternative protein alleles. The alternative two-locus beta-globin haplotypes are associated with pronounced differences in intraerythrocyte glutathione and nitric oxide metabolism, suggesting a possible mechanism for selection on hemoglobin function.
| S-EPMC2013706 | biostudies-literature