Dagmar Čížková

Parental ageing can influence offspring through non-genetic mechanisms. The contribution of epigenetic inheritance parental effects still remains poorly understood. DNA methylation is a widespread regulator of gene expression that changes during development and ageing and can also act as a mediator of intergenerational effects. We tested whether age-related changes in parental DNA methylation are transmitted to offspring in the short-lived turquoise killifish ( Nothobranchius furzeri , Cyprinodontiformes). Using reduced-representation sequencing, we quantified genome-wide DNA methylation and examined methylation dynamics at individual loci. The overall proportion of methylated CpG sites increased during early ageing but declined at later ages, revealing a non-linear trajectory with substantial among-individual variation. Despite these age-related changes, we found no evidence that parental methylation patterns were transmitted to offspring, either at the genome-wide level or at individual loci. Our findings indicate that although DNA methylation undergoes pronounced age-dependent remodelling in adult killifish, these changes are not detectably inherited by the next generation. We discuss these results in the context of epigenetic inheritance and ageing in vertebrate model systems.

Senescence is a multifactorial and individualised process of age-related physiological decline. Cellular markers, such as telomere length and DNA methylation, can reveal subtle changes associated with chronological age or expected lifespan. In this study, we evaluated the utility of fin tissue as a surrogate for assessing telomere length and proportion of DNA methylation in the gonads of a small, short-lived laboratory fish, the turquoise killifish ( Nothobranchius furzeri ). We collected fin and gonadal tissues from both females and males at three different ages. We extracted DNA to measure telomere length via terminal restriction fragment (TRF) analysis and global DNA methylation levels using double-digest restriction-associated DNA sequencing (ddRADseq). Our results show a notable correspondence between telomere length and DNA methylation patterns in fin and gonadal tissues. These findings support the use of fin biopsies as a non-lethal method for assessing ageing biomarkers in the gonads of small freshwater fish.

Parasites are expected to hybridise in similar ways to free‐living organisms, although this may be modified by their reduced genome architecture. Recombinant strains and taxa of hybrid origin can be studied in nature where hosts come into secondary contact. Here we apply genome‐wide analysis to parasites from a contact previously characterised for many individuals using classical markers. The host contact is the European house mouse hybrid zone; the parasites are lung fungus Pneumocystis and gut pinworm Syphacia . The genomic (many loci) and classical (many‐individual) results are broadly consistent in scale and centring of transitions across the host hybrid zone. Whole mitogenome comparisons confirm earlier suggestions that parasite divergence is low compared to their hosts, perhaps due to reduced‐genome stabilising selection. In the recombining genome, we are able to show blocks of the parasite genome of alternating host origin, including one Pneumocystis strain which appears to be an F3+ cross and one recombinant Syphacia strain found over multiple localities. Functional analyses of introgressing genes show enrichment for genes likely important for parasitic lifestyle. Our work confirms that evolutionary models of hybridisation apply equally to hosts and their parasites.

The house mouse, Mus musculus, is a widely used animal model in biomedical research, with classical laboratory strains (CLS) being the most frequently employed. However, the limited genetic variability in CLS hinders their applicability in evolutionary studies. Wild-derived strains (WDS), on the other hand, provide a suitable resource for such investigations. This study quantifies genetic and phenotypic data of 101 WDS representing 5 species, 3 subspecies, and 8 natural Y consomic strains and compares them with CLS. Genetic variability was estimated using whole mtDNA sequences, the Prdm9 gene, and copy number variation at two sex chromosome-linked genes. WDS exhibit a large natural variation with up to 2173 polymorphic sites in mitogenomes, whereas CLS display 92 sites. Moreover, while CLS have two Prdm9 alleles, WDS harbour 46 different alleles. Although CLS resemble M. m. domesticus and M. m. musculus WDS, they differ from them in 10 and 14 out of 16 phenotypic traits, respectively. The results suggest that WDS can be a useful tool in evolutionary and biomedical studies with great potential for medical applications.

Parasites are expected to hybridise in similar ways to free living organisms, although this may be modified by their reduced genome architecture. Recombinant strains and taxa of hybrid origin can be studied in nature where hosts come into secondary contact. Here we apply genome-wide analysis to parasites from a contact previously characterised for many individuals using classical markers. The host contact is the European house mouse hybrid zone; the parasites are lung fungus Pneumocystis and gut pinworm Syphacia. The multilocus and multi-individual datasets are broadly consistent in scale and centering. Whole mitogenome comparisons confirm earlier suggestions that parasite divergence is low compared to their hosts, perhaps due to reduced genome stabilising selection. In the recombining genome we are able to show blocks of parasite genome of alternating host origin, including one Pneumocystis strain which appears to be an F3+ cross and one recombinant Syphacia strain found over multiple localities. Functional analyses of introgressing genes show enrichment for genes likely important for parasitic lifestyle.

The gut microbiota of vertebrates is acquired from the environment and other individuals, including parents and unrelated conspecifics. In the laboratory mouse, a key animal model, inter-individual interactions are severely limited and its gut microbiota is abnormal. Surprisingly, our understanding of how inter-individual transmission impacts house mouse gut microbiota is solely derived from laboratory experiments. We investigated the effects of inter-individual transmission on gut microbiota in two subspecies of house mice (Mus musculus musculus and M. m. domesticus) raised in a semi-natural environment without social or mating restrictions. We assessed the correlation between microbiota composition (16S rRNA profiles), social contact intensity (microtransponder-based social networks), and mouse relatedness (microsatellite-based pedigrees). Inter-individual transmission had a greater impact on the lower gut (colon and cecum) than on the small intestine (ileum). In the lower gut, relatedness and social contact independently influenced microbiota similarity. Despite female-biased parental care, both parents exerted a similar influence on their offspring’s microbiota, diminishing with the offspring’s age in adulthood. Inter-individual transmission was more pronounced in M. m. domesticus, a subspecies, with a social and reproductive network divided into more closed modules. This suggests that the transmission magnitude depends on the social and genetic structure of the studied population.

The question of how interactions between the gut microbiome and vertebrate hosts contribute to host adaptation and speciation is one of the major problems in current evolutionary research. Using bacteriome and mycobiome metabarcoding, we examined how these two components of the gut microbiota vary with the degree of host admixture in secondary contact between two house mouse subspecies (Mus musculus musculus and M. m. domesticus). We used a large data set collected at two replicates of the hybrid zone and model‐based statistical analyses to ensure the robustness of our results. Assuming that the microbiota of wild hosts suffers from spatial autocorrelation, we directly compared the results of statistical models that were spatially naive with those that accounted for spatial autocorrelation. We showed that neglecting spatial autocorrelation can strongly affect the results and lead to misleading conclusions. The spatial analyses showed little difference between subspecies, both in microbiome composition and in individual bacterial lineages. Similarly, the degree of admixture had minimal effects on the gut bacteriome and mycobiome and was caused by changes in a few microbial lineages that correspond to the common symbionts of free‐living house mice. In contrast to previous studies, these data do not support the hypothesis that the microbiota plays an important role in host reproductive isolation in this particular model system.

The house mouse, Mus musculus , is a widely used animal model in biomedical research, with classical laboratory strains (CLS) being the most frequently employed. However, the limited genetic variability in CLS hinders their applicability in evolutionary studies. Wild-derived strains (WDS), on the other hand, provide a suitable resource for such investigations. This study quantifies genetic and phenotypic data of 101 WDS representing 5 species, 3 subspecies, and 8 natural Y consomic strains and compares them with CLS. Genetic variability was estimated using whole mtDNA sequences, the Prdm9 gene, and copy number variation at two sex chromosome-linked genes. WDS exhibit a large natural variation with up to 2173 polymorphic sites in mitogenomes, whereas CLS display 92 sites. Moreover, while CLS have two Prdm9 alleles, WDS harbour 46 different alleles. Although CLS resemble M. m. domesticus and M. m. musculus WDS, they differ from them in 8 and 11 out of 15 phenotypic traits, respectively. The results suggest that WDS can be a useful tool in evolutionary studies and have great potential for medical applications.

Microbiome research has gained much attention in recent years as the importance of gut microbiota in regulating host health becomes increasingly evident. However, the impact of radiation on the microbiota in the murine bone marrow transplantation model is still poorly understood. In this paper, we present the major conclusions of our investigation into the effects of radiation and subsequent bone marrow transplantation with or without T cell depletion of the donor bone-marrow on the microbiota of the ileum and cecum. Our findings show that radiation has different effects on the microbiota of the two intestinal regions, with the cecum showing increased interindividual variation, suggesting an impaired ability of the host to regulate microbial symbionts, consistent with the Anna Karenina principle. Additionally, we observed changes in the ileum composition, including an increase in bacterial taxa that are important modulators of host health, such as Akkermansia and Faecalibaculum . In contrast, radiation in the cecum was associated with an increased abundance of several common commensal taxa in the gut, including Lachnospiraceae and Bacteroides . Finally, we found that high doses of radiation had more substantial effects on the caecal microbiota of the T-cell-depleted group than that of the non-T-cell-depleted group. Overall, our results contribute to a better understanding of the complex relationship between radiation and the gut microbiota in the context of bone marrow transplantation and highlight the importance of considering different intestinal regions when studying microbiome responses to environmental stressors.

The question of how interactions between the gut microbiome and vertebrate hosts contribute to host adaptation and speciation is one of the major problems in current evolutionary research. Using bacteriome and mycobiome metabarcoding, we examined how these two components of the gut microbiota vary with the degree of host admixture in secondary contact between two house mouse subspecies ( Mus musculus musculus and M. m. domesticus ). We used a large dataset collected at two replicates of the hybrid zone and model-based statistical analyses to ensure the robustness of our results. Assuming that the microbiota of wild hosts suffers from spatial autocorrelation, we directly compared the results of statistical models that were spatially naive with those that accounted for spatial autocorrelation. We showed that neglecting spatial autocorrelation can drastically affect the results and lead to misleading conclusions. The spatial analyses showed little difference between subspecies, both in microbiome composition and in individual bacterial lineages. Similarly, the degree of admixture had minimal effects on the gut bacteriome and mycobiome and was caused by changes in a few microbial lineages that correspond to the common symbionts of free-living house mice. In contrast to previous studies, these data do not support the hypothesis that the microbiota plays an important role in host reproductive isolation in this particular model system.