Biology subjects

Moeller, A. H.

Publications and source records attributed to Moeller, A. H..

7 recordsLinked to original sources

bioRxiv2024

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.

evolutionary biology↗

bioRxiv2024

Hackflex library preparation enables low-cost metagenomic profiling

Shotgun metagenomic sequencing provides valuable insights into microbial communities, but the high cost of library preparation with standard kits and protocols is a barrier for many. New methods such as Hackflex use diluted commercially available reagents to greatly reduce library preparation costs. However, these methods have not been systematically validated for metagenomic sequencing. Here, we evaluate Hackflex performance by sequencing metagenomic libraries from known mock communities as well as mouse fecal samples prepared by Hackflex, Illumina DNA Prep, and Illumina TruSeq methods. Hackflex successfully recovered all members of the Zymo mock community, performing best for samples with DNA concentrations <1 ng/uL. Furthermore, Hackflex was able to delineate microbiota of individual inbred mice from the same breeding stock at the same mouse facility, and statistical modeling indicated that mouse ID explained a greater fraction of the variance in metagenomic composition than did library preparation method. These results show that Hackflex is suitable for generating inventories of bacterial communities through metagenomic sequencing.

microbiology↗

bioRxiv2023

Major urinary protein (Mup) gene family deletion drives sex-specific alterations on the house mouse gut microbiota

The gut microbiota is shaped by host metabolism. In house mice (Mus musculus), major urinary protein (MUP) pheromone production represents a considerable energy investment, particularly in sexually mature males. Deletion of the Mup gene family shifts mouse metabolism towards an anabolic state, marked by lipogenesis, lipid accumulation, and body mass increases. Given the metabolic implications of MUPs, they may also influence the gut microbiota. Here, we investigated the effect of deletion of the Mup gene family on the gut microbiota of sexually mature mice. Shotgun metagenomics revealed distinct taxonomic and functional profiles between wildtype and knockout males, but not females. Deletion of the Mup gene cluster significantly reduced diversity in microbial families and functions in male mice. Additionally, specific taxa of the Ruminococcaceae family, which is associated with gut health and reduced risk of developing metabolic syndrome, and several microbial functions, such as transporters involved in vitamin B5 acquisition, were significantly depleted in the microbiota of Mup-knockout males. Altogether these results show that major urinary proteins significantly affect the gut microbiota of house mouse in a sex-specific manner. ImportanceThe community of microorganisms that inhabit the gastrointestinal track of animals, known as the gut microbiota, can have profound effects on host phenotypes. The gut microbiota is in turn shaped by host genes, including those involved with host metabolism. In adult male house mice, expression of the major urinary protein (Mup) gene cluster represents a substantial energy investment, and deletion of Mup gene family leads to fat accumulation and weight gain in males. We show for the first time that deleting Mup genes also alters the gut microbiota of male, but not female, mice in terms of both taxonomic and functional composition. Male mice without Mup genes harbored fewer gut bacterial families and reduced abundances of several species, including bacteria previously shown to reduce obesity risk. Studying the impact of the Mup genes on the gut microbiota will help us understand how these genes influence host phenotype more broadly.

microbiology↗

bioRxiv2022

Adaptive remodeling of the gut microbiome over long-distance migration

The gut microbiome can be thought of as a forgotten organ, owing to its profound effects on host phenotypes. Long-distance migratory birds are capable of adaptively modulating their physiology, raising the hypothesis that the microbiome of migratory birds may undergo a parallel remodeling process that helps to meet the energetic demands of long-distance migration. To test this hypothesis, we investigated changes in gut microbiome composition and function over the fall migration of a Neotropical-Nearctic migratory Blackpoll Warbler (Setophaga striata), which exhibits one of the longest known autumnal migratory routes of any songbird and rapidly undergoes extensive physiological remodeling during migration. Overall, our results showed that the Blackpoll warbler microbiome differed significantly across phases of fall migration. This pattern was driven by a dramatic increase in the relative abundance of Proteobacteria, and more specifically a single ASV belonging to the family Enterobacteriaceae. Further, blackpolls exhibited a progressive reduction in microbiome phylogenetic diversity and within-group variances over migration, indicating convergence of microbiome composition among individuals during long-distance migration. Metagenomic analysis revealed that the gut microbiome of staging blackpolls was enriched in bacterial pathways involved in vitamin, amino acid, and fatty acid biosynthesis, as well as carbohydrate metabolism, and that these pathways were in turn positively associated with host body mass and subcutaneous fat deposits. Together, these results provide evidence that the gut microbiome of migratory birds may undergo adaptive remodeling to meet the physiological and energetic demands of long-distance migration.

ecology↗

bioRxiv2022

Local adaptation of 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 wildtype (WT) and Rag1-knockout (Rag1-/-) house mice revealed widespread fitness advantages for native gut bacteria. Certain native Bacteriodetes and Firmicutes favored by selection in WT hosts were not favored or disfavored in Rag1-/- hosts, which lack adaptive immunity, indicating that Rag1 mediates fitness advantages of these strains. This study demonstrates local adaptation of gut microbiota to a mammalian species. One-Sentence SummaryAdaptive advantages for native bacteria underlie the assembly of the mouse gut microbiota.

evolutionary biology↗

bioRxiv2022

Low-cost genomics enable high-throughput isolate screening and strain-level microbiome profiling

Earths environments harbor complex consortia of microbial lineages that affect processes ranging from host health to biogeochemical cycles. However, understanding the evolution and function of these microbiota has been limited by an inability to isolate individual microbial constituents and assemble their complete genomes in a high-throughput manner. Here, we present a workflow for bacterial isolation and whole-genome sequencing from complex microbiota using open-source labware and the OpenTrons automated liquid handling robotics platform. Our approach circumvents the need for isolate screening (e.g., through 16S rDNA sequencing or mass spectrometry analyses) by reducing the costs of genome-sequencing to ~$10 per bacterium. Applying the workflow, we quantified genomic diversity within 45 bacterial species in the chimpanzee gut microbiota. Results revealed hotspots of recombination in bacterial genomes and elevated transmission of plasmids between distantly related bacterial species within individual chimpanzee hosts. This study develops and applies an approach for high-throughput bacterial isolation and genome sequencing, enabling population genetic analyses of bacterial strains within complex communities not currently possible with metagenomic data alone.

microbiology↗

bioRxiv2022

Humanization of wildlife gut microbiota in urban environments

Urbanization is rapidly altering Earths environments, demanding investigations of the impacts on resident wildlife. Here, we show that urban populations of coyotes (Canis latrans) and crested anole lizards (Anolis cristatellus) acquire gut microbiota constituents found in humans, including the gut bacterial lineages most significantly associated with urbanization in humans (e.g., Bacteroides). Comparisons of urban and rural wildlife and human populations revealed significant convergence of the gut microbiota among urban host populations. Remarkably, all microbial lineages found in humans that were overrepresented in urban wildlife relative to rural wildlife were also overrepresented in urban humans relative to rural humans. These results indicate parallel effects of urbanization on human and wildlife gut microbiota and suggest spillover of bacteria from humans into wildlife in cities.

ecology↗