bioRxiv Science⌕ Search

Biology subjects

Dirksen, P.

Publications and source records attributed to Dirksen, P..

4 recordsLinked to original sources

CeMbio - The C. elegans microbiome resource

The study of microbiomes by sequencing has revealed a plethora of correlations between microbial community composition and various life-history characteristics of the corresponding host species. However, inferring causation from correlation is often hampered by the sheer compositional complexity of microbiomes, even in simple organisms. Synthetic communities offer an effective approach to infer cause-effect relationships in host-microbiome systems. Yet the available communities suffer from several drawbacks, such as artificial (thus non-natural) choice of microbes, microbe-host mismatch (e.g. human microbes in gnotobiotic mice), or hosts lacking genetic tractability. Here we introduce CeMbio, a simplified natural Caenorhabditis elegans microbiota derived from our previous meta-analysis of the natural microbiome of this nematode. The CeMbio resource is amenable to all strengths of the C. elegans model system, strains included are readily culturable, they all colonize the worm gut individually, and comprise a robust community that distinctly affects nematode life-history. Several tools have additionally been developed for the CeMbio strains, including diagnostic PCR primers, completely sequenced genomes, and metabolic network models. With CeMbio, we provide a versatile resource and toolbox for the in-depth dissection of naturally relevant host-microbiome interactions in C. elegans. Dataset accession numbersWhole genome sequencing data (PRJNA624308); microbiome sequencing [PRJEB37101 and PRJEB37035]; data supplement on the GSA Figshare Portal.

microbiology↗

The inducible response of the nematode Caenorhabditis elegans to members of its natural microbiome across development and adult life

The biology of all organisms is influenced by the associated community of microorganisms. In spite of its importance, it is usually not well understood how exactly this microbiome affects host functions and what are the underlying molecular processes. To rectify this knowledge gap, we took advantage of the nematode C. elegans as a tractable, experimental model system and assessed the inducible transcriptome response after colonization with members of its native microbiome. For this study, we focused on two isolates of the genus Ochrobactrum. These bacteria are known to be abundant in the nematodes microbiome and are capable of colonizing and persisting in the nematode gut, even under stressful conditions. The transcriptome response was assessed across development and three time points of adult life, using general and C. elegans-specific enrichment analyses to identify affected functions. Our assessment revealed an influence of the microbiome members on the nematodes dietary response, development, fertility, immunity, and energy metabolism. This response is mainly regulated by a GATA transcription factor, most likely ELT-2, as indicated by the enrichment of (i) the GATA motif in the promoter regions of inducible genes and (ii) of ELT-2 targets among the differentially expressed genes. We compared our transcriptome results with a corresponding previously characterized proteome data set, highlighting a significant overlap in the differentially expressed genes and the affected functions. Our analysis further identified a core set of 86 genes that consistently responded to the microbiome members across development and adult life, including several C-type lectin-like genes and genes known to be involved in energy metabolism or fertility. We additionally assessed the consequences of induced gene expression with the help of metabolic network model analysis, using a previously established metabolic network for C. elegans. This analysis complemented the enrichment analyses by revealing an influence of the Ochrobactrum isolates on C. elegans energy metabolism and furthermore metabolism of specific amino acids, fatty acids, and also folate biosynthesis. Our findings highlight the multifaceted impact of naturally colonizing microbiome isolates on C. elegans life history and thereby provide a framework for further analysis of microbiome-mediated host functions.

evolutionary biology↗

A multi-parent recombinant inbred line population of Caenorhabditis elegans enhances mapping resolution and identification of novel QTLs for complex life-history traits

Local populations of the bacterivorous nematode Caenorhabditis elegans can be genetically almost as diverse as global populations. To investigate the effect of local genetic variation on heritable traits, we developed a new recombinant inbred line (RIL) population derived from four wild isolates. The wild isolates were collected from two closely located sites in France: Orsay and Santeuil. By crossing these four genetically diverse parental isolates a population of 200 RILs was constructed. RNA-seq was used to obtain sequence polymorphisms identifying almost 9000 SNPs variable between the four genotypes with an average spacing of 11 kb, possibly doubling the mapping resolution relative to currently available RIL panels. The SNPs were used to construct a genetic map to facilitate QTL analysis. Life history traits, such as lifespan, stress resistance, developmental speed and population growth were measured in different environments. For most traits substantial variation was found, and multiple QTLs could be detected, including novel QTLs not found in previous QTL analysis, for example for lifespan or pathogen responses. This shows that recombining genetic variation across C. elegans populations that are in geographical close proximity provides ample variation for QTL mapping. Taken together, we show that RNA-seq can be used for genotyping, that using more parents than the classical two parental genotypes to construct a RIL population facilitates the detection of QTLs and that the use of wild isolates permits analysis of local adaptation and life history trade-offs.

genetics↗

The Neutral Metaorganism

Almost all animals and plants are inhabited by diverse communities of microorganisms, the microbiota. The hosts often pose highly selective environments, which only a subset of the environmentally available microbes are able to colonize. From the hosts perspective it seems useful to shape the community composition of these allowed microbes to promote a beneficial host-microbe symbiosis. In contrast to this, neutral models assume that the structure of the microbiota is entirely shaped by random population dynamics and dispersal. We here show that microbiota community structure from a wide range of host organisms, in particular including previously understudied invertebrates, is in almost all cases consistent with neutral expectations. Moreover, we demonstrate that apparent discrepancies with the neutral model can be due to transient community states rather than host selection. In conclusion, even though hosts are often assumed to control microbiota composition to ensure beneficial interactions, our broad-scale analysis highlights that following colonization, it could rather be neutral processes that determine microbial community structure.

ecology↗