Mus Musculus Domesticus Research Articles

T. Muris Infection Dynamics of a Fresh, Wild Isolate: Is the Established E Isolate Still Relevant?

For decades, parasitic worms such as Trichuris muris have been maintained in laboratory animals, providing insights into host-parasite interactions and host immune responses. The most used T. muris isolate is the E isolate, established in the laboratory in 1954. However, one concern with these model systems is the potential for laboratory-induced selection and therefore changes in host-parasite interactions. To address these concerns, we compare the E isolate with a recently isolated T. muris isolate (M isolate), established from wild house mice (Mus musculus domesticus, Isle of May, UK), in their capacity to infect laboratory mice. High dose infection of C57BL/6 mice revealed that significantly more parasites of the M isolate survived to the adult stage compared to the E isolate. Worm persistence was associated with heightened TNF-α and IL-10 secretion upon parasite-specific re-stimulation, and higher serum IgG1 and IgG2c levels, concomitant with an increase in T-bet+ and ICOS+ CD4+ T effector-memory cells. Differences in host response to the isolates were not as pronounced during low dose infection. Our study highlights the need for regular evaluation of lab-maintained parasite isolates against freshly isolated parasites to understand whether the established lab strains remain relevant model systems for our understanding of parasitic infections.

Egalitarian cooperation linked to central oxytocin levels in communal breeding house mice

Relationships between adult females are fundamental to understanding diversity in animal social systems. While cooperative relationships between kin are known to promote fitness benefits, the proximate mechanisms underlying this are not well understood. Here we show that when related female house mice (Mus musculus domesticus) cooperate to rear young communally, those with higher endogenous oxytocin levels have more egalitarian and successful cooperative relationships. Sisters with higher oxytocin concentrations in the paraventricular nucleus (PVN) of the hypothalamus weaned significantly more offspring, had lower reproductive skew and spent more equal proportions of time in the nest. By contrast, PVN oxytocin was unrelated to the number of weaned offspring produced in the absence of cooperation, and did not vary in response to manipulation of nest site availability or social cues of outgroup competition. By linking fitness consequences of cooperation with oxytocin, our findings have broad implications for understanding the evolution of egalitarian social relationships.

A survey of VKORC1 missense mutations in eleven Italian islands reveals widespread rodenticide resistance in house mice

To protect native wildlife, more than one hundred rodent eradications have been attempted in the Mediterranean islands by using anticoagulant rodenticides (ARs). Despite their high efficiency, resistance to ARs has been observed in many countries and it is mostly related to missense mutations (SNPs) in the VKORC1 gene. The presence of resistant individuals reduces the efficiency of rodent management, leading to an excessive use of ARs. Thus, the risk of poisoning in non-target species increases. In this study, the first survey of ARs resistance in the house mouse Mus domesticus covering multiple islands in the Mediterranean was performed. Tissue samples of eighty-two mice from eleven islands in Italy were analysed and eight missense SNPs were found. In addition to some well-known missense mutations, such as Tyr139Cys, six new missense SNPs for the house mouse were discovered, four of which were new even for any rodent species. Furthermore, the frequency of Tyr139Cys significantly increased in Ventotene Island after a four-year long rat eradication. This could be due to the selective pressure of ARs that allowed the mice carrying the mutation to survive. This study demonstrates once again the importance of assessing resistance to ARs before undertaking rodent eradications. Indeed, this would allow an informed decision of the most effective AR to use, maximizing the success rate of the eradications and minimizing secondary poisoning and other deleterious effects for non-target species and the environment.

Climate influences the gut eukaryome of wild rodents in the Great Rift Valley of Jordan

BackgroundThe mammalian gut microbiome includes a community of eukaryotes with significant taxonomic and functional diversity termed the eukaryome. The molecular analysis of eukaryotic diversity in microbiomes of wild mammals is still in its early stages due to the recent emergence of interest in this field. This study aimed to fill this knowledge gap by collecting data on eukaryotic species found in the intestines of wild rodents. Because little is known about the influence of climate on the gut eukaryome, we compared the composition of the gut eukaryotes in two rodent species, Mus musculus domesticus and Acomys cahirinus, which inhabit a transect crossing a temperate and tropical zone on the Jordanian side of the Great Rift Valley (GRV).MethodsWe used high-throughput amplicon sequencing targeting the 18S rRNA gene in fecal samples from rodents to identify eukaryotic organisms, their relative abundance, and their potential for pathogenicity.ResultsNematodes and protozoa were the most prevalent species in the eukaryome communities, whereas fungi made up 6.5% of the total. Sixty percent of the eukaryotic ASVs belonged to taxa that included known pathogens. Eighty percent of the rodents were infected with pinworms, specifically Syphacia obvelata. Eukaryotic species diversity differed significantly between bioclimatic zones (p = 0.001). Nippostrongylus brasiliensis and Aspiculuris tetraptera were found to be present exclusively in the Sudanian zone rodents. This area has not reported any cases of Trichuris infections. Yet, Capillaria infestations were unique to the Mediterranean region, while Trichuris vulpis infestations were also prevalent in the Mediterranean and Irano-Turanian regions.ConclusionsThis study highlights the importance of considering host species diversity and environmental factors when studying eukaryome composition in wild mammals. These data will be valuable as a reference to eukaryome study.Graphical

Recent genetic drift in the co-diversified gut bacterial symbionts of laboratory mice.

Laboratory mice (Mus musculus domesticus) harbor gut bacterial strains that are distinct from those of wild mice1 but whose evolutionary histories are poorly understood. Understanding the divergence of laboratory-mouse gut microbiota (LGM) from wild-mouse gut microbiota (WGM) is critical, because LGM and WGM have been previously shown to differentially affect mouse immune-cell proliferation2,3, infection resistance4, cancer progression2, and ability to model drug outcomes for humans5. Here, we show that laboratory mice have retained gut bacterial symbiont lineages that diversified in parallel (co-diversified) with rodent species for > 25 million years, but that LGM strains of these ancestral symbionts have experienced accelerated accumulation of genetic load during the past ~ 120 years of captivity. Compared to closely related WGM strains, co-diversified LGM strains displayed significantly faster genome-wide rates of fixation of nonsynonymous mutations, indicating elevated genetic drift, a difference that was absent in non-co-diversified symbiont clades. Competition experiments in germ-free mice further indicated that LGM strains within co-diversified clades displayed significantly reduced fitness in vivo compared to WGM relatives to an extent not observed within non-co-diversified clades. Thus, stochastic processes (e.g., bottlenecks), not natural selection in the laboratory, have been the predominant evolutionary forces underlying divergence of co-diversified symbiont strains between laboratory and wild house mice. Our results show that gut bacterial lineages conserved in diverse rodent species have acquired novel mutational burdens in laboratory mice, providing an evolutionary rationale for restoring laboratory mice with wild gut bacterial strain diversity.

Across two continents: The genomic basis of environmental adaptation in house mice (Mus musculus domesticus) from the Americas.

Replicated clines across environmental gradients can be strong evidence of adaptation. House mice (Mus musculus domesticus) were introduced to the Americas by European colonizers and are now widely distributed from Tierra del Fuego to Alaska. Multiple aspects of climate, such as temperature, vary predictably across latitude in the Americas. Past studies of North American populations across latitudinal gradients provided evidence of environmental adaptation in traits related to body size, metabolism, and behavior and identified candidate genes using selection scans. Here, we investigate genomic signals of environmental adaptation on a second continent, South America, and ask whether there is evidence of parallel adaptation across multiple latitudinal transects in the Americas. We first identified loci across the genome showing signatures of selection related to climatic variation in mice sampled across a latitudinal transect in South America, accounting for neutral population structure. Consistent with previous results, most candidate SNPs were in putatively regulatory regions. Genes that contained the most extreme outliers relate to traits such as body weight or size, metabolism, immunity, fat, eye function, and the cardiovascular system. We then compared these results with the results of analyses of published data from two transects in North America. While most candidate genes were unique to individual transects, we found significant overlap among candidate genes identified independently in the three transects. These genes are diverse, with functions relating to metabolism, immunity, cardiac function, and circadian rhythm, among others. We also found parallel shifts in allele frequency in candidate genes across latitudinal gradients. Finally, combining data from all three transects, we identified several genes associated with variation in body weight. Overall, our results provide strong evidence of shared responses to selection and identify genes that likely underlie recent environmental adaptation in house mice across North and South America.

The adaptive immune response to Trichuris in wild versus laboratory mice: An established model system in context.

Laboratory model organisms have provided a window into how the immune system functions. An increasing body of evidence, however, suggests that the immune responses of naive laboratory animals may differ substantially to those of their wild counterparts. Past exposure, environmental challenges and physiological condition may all impact on immune responsiveness. Chronic infections of soil-transmitted helminths, which we define as establishment of adult, fecund worms, impose significant health burdens on humans, livestock and wildlife, with limited treatment success. In laboratory mice, Th1 versus Th2 immune polarisation is the major determinant of helminth infection outcome. Here we compared antigen-specific immune responses to the soil-transmitted whipworm Trichuris muris between controlled laboratory and wild free-ranging populations of house mice (Mus musculus domesticus). Wild mice harbouring chronic, low-level infections produced lower levels of cytokines in response to Trichuris antigen than laboratory-housed C57BL/6 mice. Wild mouse effector/memory CD4+ T cell phenotype reflected the antigen-specific cytokine response across the Th1/Th2 spectrum. Increasing egg shedding was associated with body condition loss. However, local Trichuris-specific Th1/Th2 balance was positively associated with worm burden only in older wild mice. Thus, although the fundamental relationships between the CD4+ T helper cell response and resistance to T. muris infection are similar in both laboratory and wild M. m. domesticus, there are quantitative differences and age-specific effects that are analogous to human immune responses. These context-dependent immune responses demonstrate the fundamental importance of understanding the differences between model and natural systems for translating mechanistic models to 'real world' immune function.

Into the Wild: A novel wild-derived inbred strain resource expands the genomic and phenotypic diversity of laboratory mouse models.

The laboratory mouse has served as the premier animal model system for both basic and preclinical investigations for over a century. However, laboratory mice capture only a subset of the genetic variation found in wild mouse populations, ultimately limiting the potential of classical inbred strains to uncover phenotype-associated variants and pathways. Wild mouse populations are reservoirs of genetic diversity that could facilitate the discovery of new functional and disease-associated alleles, but the scarcity of commercially available, well-characterized wild mouse strains limits their broader adoption in biomedical research. To overcome this barrier, we have recently developed, sequenced, and phenotyped a set of 11 inbred strains derived from wild-caught Mus musculus domesticus. Each of these "Nachman strains" immortalizes a unique wild haplotype sampled from one of five environmentally distinct locations across North and South America. Whole genome sequence analysis reveals that each strain carries between 4.73-6.54 million single nucleotide differences relative to the GRCm39 mouse reference, with 42.5% of variants in the Nachman strain genomes absent from current classical inbred mouse strain panels. We phenotyped the Nachman strains on a customized pipeline to assess the scope of disease-relevant neurobehavioral, biochemical, physiological, metabolic, and morphological trait variation. The Nachman strains exhibit significant inter-strain variation in >90% of 1119 surveyed traits and expand the range of phenotypic diversity captured in classical inbred strain panels. These novel wild-derived inbred mouse strain resources are set to empower new discoveries in both basic and preclinical research.

A working model for the formation of Robertsonian chromosomes.

Robertsonian chromosomes form by fusion of two chromosomes that have centromeres located near their ends, known as acrocentric or telocentric chromosomes. This fusion creates a new metacentric chromosome and is a major mechanism of karyotype evolution and speciation. Robertsonian chromosomes are common in nature and were first described in grasshoppers by the zoologist W. R. B. Robertson more than 100 years ago. They have since been observed in many species, including catfish, sheep, butterflies, bats, bovids, rodents and humans, and are the most common chromosomal change in mammals. Robertsonian translocations are particularly rampant in the house mouse, Mus musculus domesticus, where they exhibit meiotic drive and create reproductive isolation. Recent progress has been made in understanding how Robertsonian chromosomes form in the human genome, highlighting some of the fundamental principles of how and why these types of fusion events occur so frequently. Consequences of these fusions include infertility and Down's syndrome. In this Hypothesis, I postulate that the conditions that allow these fusions to form are threefold: (1) sequence homology on non-homologous chromosomes, often in the form of repetitive DNA; (2) recombination initiation during meiosis; and (3) physical proximity of the homologous sequences in three-dimensional space. This Hypothesis highlights the latest progress in understanding human Robertsonian translocations within the context of the broader literature on Robertsonian chromosomes.

Epigenetic age estimation of wild mice using faecal samples.

Age is a key parameter in population ecology, with a myriad of biological processes changing with age as organisms develop in early life then later senesce. As age is often hard to accurately measure with non-lethal methods, epigenetic methods of age estimation (epigenetic clocks) have become a popular tool in animal ecology and are often developed or calibrated using captive animals of known age. However, studies typically rely on invasive blood or tissue samples, which limit their application in more sensitive or elusive species. Moreover, few studies have directly assessed how methylation patterns and epigenetic age estimates compare across environmental contexts (e.g. captive or laboratory-based vs. wild animals). Here, we built a targeted epigenetic clock from laboratory house mice (strain C57BL/6, Mus musculus) using DNA from non-invasive faecal samples, and then used it to estimate age in a population of wild mice (Mus musculus domesticus) of unknown age. This laboratory mouse-derived epigenetic clock accurately predicted adult wild mice to be older than juveniles and showed that wild mice typically increased in epigenetic age over time, but with wide variation in epigenetic ageing rate among individuals. Our results also suggested that, for a given body mass, wild mice had higher methylation across targeted CpG sites than laboratory mice (and consistently higher epigenetic age estimates as a result), even among the smallest, juvenile mice. This suggests wild and laboratory mice may display different CpG methylation levels from very early in life and indicates caution is needed when developing epigenetic clocks on laboratory animals and applying them in the wild.

An attempt to evidence post-fire adaptation of red fox diet in a Mediterranean area

Although fires are common in Mediterranean ecosystems, there are substantial knowledge gaps regarding post-fire shifts in animal diets, especially for carnivores. Red fox Vulpes vulpes is a generalist medium-size carnivore known to have a positive post-fire response, probably due to increased prey availability or facility to hunt. As small mammals are often one of its primary food categories, and early successional visitors of post-fire habitats, we hypothesize a change in red fox diet composition in the warm season after a fire. Hair trapping and scat collection were used to investigate selection of small mammals in a typical Mediterranean region, 3 years after a fire. The diet composition of the fox was compared with that of the fox in the same area in 1992, and with other undisturbed Mediterranean areas. Diet selection was evaluated through the Forage ratio and single resource preference tests. Red fox diet was consistent with other Mediterranean areas, with fruits and seeds, invertebrates, and small mammals being the most consumed categories. However, small mammals were consumed significantly less than in 1992, while fruits and seeds significantly more. Resource selection analysis indicated avoidance for some ground-foraging small mammals, including Crocidura spp. house mouse Mus domesticus and voles, whereas Apodemus spp. were selected. Arboreal-foraging species, e.g. red squirrel Sciurus vulgaris and garden dormouse Eliomys quercinus were used in proportion to their availability. We concluded that this mesocarnivore had high feeding plasticity and exploited various resources according to their availability and catchability. Future studies are needed to further investigate red fox and other carnivores’ food shifts after fire disturbance, including various seasons, other successional stages and competition within predator guilds.

Natural variation in the zinc-finger-encoding exon of Prdm9 affects hybrid sterility phenotypes in mice.

PRDM9-mediated reproductive isolation was first described in the progeny of Mus musculus musculus (MUS) PWD/Ph and Mus musculus domesticus (DOM) C57BL/6J inbred strains. These male F1 hybrids fail to complete chromosome synapsis and arrest meiosis at prophase I, due to incompatibilities between the Prdm9 gene and hybrid sterility locus Hstx2. We identified 14 alleles of Prdm9 in exon 12, encoding the DNA-binding domain of the PRDM9 protein in outcrossed wild mouse populations from Europe, Asia, and the Middle East, 8 of which are novel. The same allele was found in all mice bearing introgressed t-haplotypes encompassing Prdm9. We asked whether 7 novel Prdm9 alleles in MUS populations and the t-haplotype allele in 1 MUS and 3 DOM populations induce Prdm9-mediated reproductive isolation. The results show that only combinations of the dom2 allele of DOM origin and the MUS msc1 allele ensure complete infertility of intersubspecific hybrids in outcrossed wild populations and inbred mouse strains examined so far. The results further indicate that MUS mice may share the erasure of PRDM9msc1 binding motifs in populations with different Prdm9 alleles, which implies that erased PRDM9 binding motifs may be uncoupled from their corresponding Prdm9 alleles at the population level. Our data corroborate the model of Prdm9-mediated hybrid sterility beyond inbred strains of mice and suggest that sterility alleles of Prdm9 may be rare.

Inter-subspecies mouse F1 hybrid embryonic stem cell lines newly established for studies of allelic imbalance in gene expression.

Allele-specific monoallelic gene expression is a unique phenomenon and a great resource for analyzing gene regulation. To study this phenomenon, we established new embryonic stem (ES) cell lines derived from F1 hybrid blastocysts from crosses between four mouse subspecies (Mus musculus domesticus, C57BL/6; M. musculus molossinus, MSM/Ms; M. musculus musculus, PWK; M. musculus castaneus, HMI/Ms) and analyzed the expression levels of undifferentiated pluripotent stem cell markers and karyotypes of each line. To demonstrate the utility of our cell lines, we analyzed the allele-specific expression pattern of the Inpp5d gene as an example. The allelic expression depended on the parental alleles; this dependence could be a consequence of differences in compatibility between cis- and trans-elements of the Inpp5d gene from different subspecies. The use of parental mice from four subspecies greatly enhanced genetic polymorphism. The F1 hybrid ES cells retained this polymorphism not only in the Inpp5d gene, but also at a genome-wide level. As we demonstrated for the Inpp5d gene, the established cell lines can contribute to the analysis of allelic expression imbalance based on the incompatibility between cis- and trans-elements and of phenotypes related to this incompatibility.

Alternative splicing and environmental adaptation in wild house mice.

A major goal of evolutionary genetics is to understand the genetic and molecular mechanisms underlying adaptation. Previous work has established that changes in gene regulation may contribute to adaptive evolution, but most studies have focused on mRNA abundance and only a few studies have investigated the role of post-transcriptional processing. Here, we use a combination of exome sequences and short-read RNA-Seq data from wild house mice (Mus musculus domesticus) collected along a latitudinal transect in eastern North America to identify candidate genes for local adaptation through alternative splicing. First, we identified alternatively spliced transcripts that differ in frequency between mice from the northern-most and southern-most populations in this transect. We then identified the subset of these transcripts that exhibit clinal patterns of variation among all populations in the transect. Finally, we conducted association studies to identify cis-acting splicing quantitative trait loci (cis-sQTL), and we identified cis-sQTL that overlapped with previously ascertained targets of selection from genome scans. Together, these analyses identified a small set of alternatively spliced transcripts that may underlie environmental adaptation in house mice. Many of these genes have known phenotypes associated with body size, a trait that varies clinally in these populations. We observed no overlap between these genes and genes previously identified by changes in mRNA abundance, indicating that alternative splicing and changes in mRNA abundance may provide separate molecular mechanisms of adaptation.

The Variations of Carbonic Anhdrase in Species of the Genera of $Mus$ Linnaeus, 1758 and $Rattus$ Fischer, 1803 (Mammalia: Rodentia) in the Line of Ankara - Zonguldak Provinces

Carbonic anhydrase (CA1) enzyme variations of one hundred and forty six specimens of $Mus domesticus$, $Mus macedonicus$ (House mice) and one hundred and twenty specimens of $Rattus rattus$ (Roof rat) and $Rattus norvegicus$ (Brown rat) were examined by the field work conducted in 23 localities in the line of Ankara-BoluZonguldak. It was determined that CA1 was fixed to two different homozygous alleles in both house mouse species. In the roof rat samples, CA1 was fixed to two homozygous alleles at different frequencies in two groups formed according to the colour of the back fur. A single homozygous allele was detected at the CA1 locus of brown rat samples. It was observed that these four species were separated in the UPGMA tree made according to allele frequencies. In this respect, it was evaluated that CA1 could be a molecular marker that can be used to distinguish these species.

Comparative Skull and Mandible Geometric Morphometrics of Two Species of Mice, Mus domesticus and Mus macedonicus (Muridae, Rodentia) in Turkey

Using a geometric morphometrics approach, we examined shape and size variations of skull and mandible bone of two evolutionarily distantly related mice from Turkey: Mus domesticus and Mus macedonicus. PCA analyses revealed overlap in dorsal cranium and mandible shapes of both species, consistent with previous traditional morphological methods. The skull of M. macedonicus seems to be larger in size than M. domesticus according to box-plot analyses of centroid size values, however there is no obvious difference for the mandible. No difference was observed between sexes in either of the characters. We suggest that future studies focus on dental characteristics and also consider the variation among local populations and ecological variables.

Does good food make male mice sexy? The influence of diet on male sexually selected traits

Diet may have an important influence on life history and behavioral traits involved in sexual selection. Males of high condition should be better able to bear the costs of high trait expression and hence express more elaborate sexual signals. Here, we follow Mus musculus domesticus raised in semi-natural conditions across four generations of standard (SQ) versus high quality (HQ) food, containing a higher energy level and manufactured to boost body condition during reproduction. We investigate multivariate effects on life history, pre- and post-copulatory traits of males. In addition, we investigate the effects of a food switch in the third generation on trait expression. From the F3 generation on, HQ males were more dominant. This resulted in HQ males being preferred in mate choice even though no post-copulatory traits were affected, suggesting a condition-dependent allocation to different traits. Sons of food switched males showed reduced pre- but not post-copulatory trait expression, irrespective of the direction of the food switch, indicating a mismatch rather than adaptive plastic adjustments in the first generation. We conclude that males balance investment into different traits based on the diet to achieve similar fitness. Furthermore, we show that adaptive shifts in male reproductive strategies need several generations to emerge while first responses to changing environments reflect a constrained trait expression.

Metabolism effector links in diet-induced and genetically-based obesity: A full-transcriptome study of liver tissue in experimental models in rodents

Background. When developing methods for personalized diet therapy of obesity, an urgent task is to study the molecular genetics features of the obesity pathogenesis using in vivo experimental models in laboratory animals.The aim. To determine metabolism effector links in obesity based on a comparative analysis of full-transcriptome profiles of the liver tissue of mice and rats of various strains.Materials and methods. We carried out a comparative analysis of the changes in liver transcriptome in rats and mice fed with diets of excessive energy value and exerting lipogenic effect. Data of full-transcriptome profiling using DNA microarray technology have been presented previously in 8 publications. Results. In three strains of mice treated with a high-carbohydrate high-fat diet (HCHFD), a significant differential expression (DE) of 1849 genes was revealed, of which 74 genes responded jointly in at least two groups of animals. In Wistar and Zuckerfa rats, 2109 genes responded to the consumption of HCHFD, of which 242 genes responded jointly in two groups of animals. For rodents different in genetic predisposition to the development of diet-induced obesity, the groups of genes that responded with the opposite sign of DE (depending on the genotype) in reaction to the consumption of HCHFD were identified. Bioinformatical analysis allowed establishing the presence of 43 metabolic pathways, which are targeted for the applied experimental diets exposure, in rats and 77 pathways – in mice. Four of these pathways – the pathway of retinoid metabolism, PPAR signaling pathway associated with it the previous one, xenobiotics metabolism and drugs metabolism mediated by cytochrome P450 system – responded in all groups of animals (except for female mice). The importance of the expression of Tat gene encoding tyrosine aminotransferase in the modulation of biogenic amines synthesis in diet-induced obesity was shown, which may represent a new neurometabolic regulatory function of the liver in response to the consumption of high-calorie diets. Conclusion. The analysis of the results of full-transcriptome studies showed that within each studied species (Rattus rattus and Mus domesticus) and animal sex, a number of genetic variants with a greater or lesser predisposition to the development of diet-induced obesity phenotype can be identified; and at the same time, within these variants, there is a largely similar pattern in the response of metabolism effector links to hypercaloric dietary intake. This pattern creates new prospects for translating the results of transcriptomic and metabolomic studies of laboratory animals into clinical practice in order to substantiate new approaches to personalized diet therapy of alimentary dependent diseases in patients with different genetic predisposition to obesity.

The genetics of immune and infection phenotypes in wild mice, Mus musculus domesticus.

Wild animals are under constant threat from a wide range of micro- and macroparasites in their environment. Animals make immune responses against parasites, and these are important in affecting the dynamics of parasite populations. Individual animals vary in their anti-parasite immune responses. Genetic polymorphism of immune-related loci contributes to inter-individual differences in immune responses, but most of what we know in this regard comes from studies of humans or laboratory animals; there are very few such studies of wild animals naturally infected with parasites. Here we have investigated the effect of single nucleotide polymorphisms (SNPs) in immune-related loci (the major histocompatibility complex [MHC], and loci coding for cytokines and Toll-like receptors) on a wide range of immune and infection phenotypes in UK wild house mice, Mus musculus domesticus. We found strong associations between SNPs in various MHC and cytokine-coding loci on both immune measures (antibody concentration and cytokine production) and on infection phenotypes (infection with mites, worms and viruses). Our study provides a comprehensive view of how polymorphism of immune-related loci affects immune and infection phenotypes in naturally infected wild rodent populations.

Home-site advantage for host species-specific gut microbiota.

Mammalian species harbor compositionally distinct gut microbial communities, but the mechanisms that maintain specificity of symbionts to host species remain unclear. Here, we show that natural selection within house mice (Mus musculus domesticus) drives deterministic assembly of the house-mouse gut microbiota from mixtures of native and non-native microbiotas. Competing microbiotas from wild-derived lines of house mice and other mouse species (Mus and Peromyscus spp.) within germ-free wild-type (WT) and Rag1-knockout (Rag1-/-) house mice revealed widespread fitness advantages for native gut bacteria. Native bacterial lineages significantly outcompeted non-native lineages in both WT and Rag1-/- mice, indicating home-site advantage for native microbiota independent of host adaptive immunity. However, a minority of native Bacteriodetes and Firmicutes favored by selection in WT hosts were not favored or disfavored in Rag1-/- hosts, indicating that Rag1 mediates fitness advantages of these strains. This study demonstrates home-site advantage for native gut bacteria, consistent with local adaptation of gut microbiota to their mammalian species.